Bing Hong CHEN et al. 第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 01
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第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 1目錄ÍndiceContentsGlobal trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis血液透析患者高磷血症與治療依從性的相關性研究Relative study of hyperphosphatemia and treatment adherence of patients undergoing hemodialysis39 例成人住院艱難擬梭菌感染相關性腹瀉的臨床特徵分析Clinical characteristics of Clostridioides difficile-associated diarrhea: analysis of 39 adult inpatients 基於 PI-RADSV2.1 對比雙參數與多參數 MRI 在前列腺癌的診斷價值Diagnostic value of biparametric MRI and multiparametric MRI based on PI-RADS V2.1 in prostate cancer澳門乳腺癌篩查的模式探討Exploring the future of breast cancer screening in MacaoAssessment in quality of life of patients receiving palliative care service in Macao Kiang Wu HospitalA review on pityriasis rubra pilarisBing Hong CHEN Hoi Ioi NG Yan KE Wei ZHANG Gui Qi WANG江麗詩 劉可 歐妙玲Lai Si KONG Ke LIU Mio Leng AU張進文 朱雪茵 余漢濠Jin Wen ZHANG Xue Yin ZHU Hon Ho YU鄧小雯 馬春林 伍玲 彭靜嫻 戴慧明 謝學斌Xiao Wen DENG Chun Lin MA Ling WU Ching Han PANG Wai Meng TAI Xue Bin XIE談光濠 段耀菲 劉百球 彭祥佑 檀韜Kwong Ho TAM Yao Fei DUAN Edmundo Patricío LOPES LAO Cheong Iao PANG Patrick Tao TANWai Tan YUNG Tammy See Kit LO Raymond Cheng Man CHAN Qing Xin XU Yan SUN Sai Hang LEONG Si Wai LAM Sio Leng WONG Hou Man LO Wo On CHAO Hong ZHANG03182532494156
澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal2Advances in the treatment and prevention of neonatal respiratory distress syndromeDirect transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repairUn Kei CHAN Yi Lian YE Cheong U KUOK Gang Zhu LIANG Chon Man IEONG 6775A case report of pulmonary epithelioid hemangioendothelioma外傷性頸內動脈海綿竇瘺 1 例報道A case of button battery in the esophagus in childrenFetal bronchopulmonary sequestration with pleural effusion and intrauterine therapyMimics of inguinal hernia in pregnancy: round ligament varicosities Two clinical cases of 46xy karyotype in phenotypic females: disorders of sex development or a different diagnosis?COVID-19 infection induced acute laryngitis or laryngitis caused by SARS-CoV-2/Omicron variant infectionYi LIN Thazin HLAING Chi Leong LAM Sio In WONG施偉達 譚文斌 鍾景生 梁溢貞 江瑞洲Wai I CHOI Chi Shing KWOK Si Man LEONG Io Hong CHOUI Sam LOI Chin Wan LEONG Jose COSTA MAIA Isabel CVP AFONSO Kin Veng KOON Wai CHIN In Fong LAMUt Man IONG Ki Man PAI Xian Zhong WANG Xin Ye CHEN Wan Pang SAM Tin Seak MOK Guo Liang ZHANG Chon Man KAN Cheong Un SIO Kit Ian LIO 82869196103108112
Bing Hong CHEN et al. 第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 3Global trends of artificial intelligence-assisted colonoscopy in the last 20 years:a bibliometric analysisAbstractObjective: With the emergence and rapid development of Artificial Intelligence (AI), AI-assisted applications have yielded exceptionally promising results in medical research, particularly in the field of colonoscopy. Early diagnosis and treatment of cancer have become a public health priority. This article aims to analyze current scientific achievements regarding the role of AI in colonoscopy, providing new ideas for further research. Methods: We retrieved publications from 2000 to 2021 from the Web of Science Core Collection (WoSCC), screening them based on inclusion criteria. We used CiteSpace 5.8.R3c and Microsoft Excel 2019 to evaluate and visualize the results, analyzing countries/regions, institutions, journals, authors, co-cited references, and keywords. Results: A total of 460 relevant papers were included. The number of papers increased steadily over the years, with the USA being the most productive country. The most productive institutions were Showa University and the University of Oslo, and the leading researcher was Yuichi Mori. The result of keyword analysis categorized all studies into five clusters: “Artificial Intelligence”,“polyp detection”,“water exchange”,“colorectal cancer”and“deep learning”. The current research hotspots were“Convolutional Neural Networks”, “Inflammatory Bowel Disease” and “Computer-aided Diagnosis”.Conclusions: Overall, with mounting evidence demonstrating the reliable role of AI in colonoscopy, auxiliary diagnosis of various intestinal diseases may become the primary focus of future research. Given the increasing prevalence of colorectal cancer, AI-assisted colonoscopy represents a potential research hotspot.Keywords: Global Trends; Artificial Intelligence; Colonoscopy; Bibliometric Analysis; Citespace1Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China2Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China*These authors have contributed equally to this work and share first authorship.#Correspondence to: Gui Qi WANG, Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaBing Hong CHEN1*, Hoi Ioi NG2*, Yan KE2, Wei ZHANG1 , Gui Qi WANG2#
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal41. IntroductionWith the aging of the population and changes in people’s lifestyles, the incidence and mortality rates of colorectal cancer (CRC) have increased signif icantly worldwide. The development of colonoscopy and the popular iza t ion of ear ly diagnosis and treatment are considered reliable measures to reduce both the incidence and mortality of CRC [1]. However, diagnosis and treatment of CRC in underdeveloped areas remain a social problem. The different levels of endoscopists and the uneven quality of operations lead to a certain degree of missed and misdiagnosed colonoscopies [2]. The risk of interval colorectal cancer still exists [3]. With the development of colonoscopy, Narrow-Band-Imaging (NBI), magnified endoscopy, chromoendoscopy, and endoscopic ultrasonography (EUS) have emerged to help improve the early cancer detection rate [4]. However, the lack of veteran endoscopists and the lack of experience in lesion identification are still pressing issues that need to be addressed. Accordingly, the application of art i f icial intel l igence (AI) in colonoscopy becomes a powerful assistive device in clinical practice. The concepts of AI were formally introduced in 1956 and rapid ly developed as a cut t ing-edge in tegra ted d isc ip l ine tha t incorpora ted computer science, stat ist ics, brain neurology, social sciences, and the field of gastrointestinal endoscopy, especially colonoscopy [5]. The current application of AI in colonoscopy is more about building convolutional neural networks (CNNs), a model consisting of multiple layers of simple computational nodes that mimic the activity of the human visual cortex through complex connections to learn more advanced features to aid in the detection of lower gastrointestinal lesions. AI can assist in the fields of evaluating bowel preparation scores, improving quality control of colonoscopy site identification, and improving the adenoma detection ra te (ADR) with promising resul ts [6 ,7] .The application of AI in the gastrointestinal endoscopy field is playing an epic and transformative role. The latest progress and the most important contributions of AI in colonoscopy can be found in the surging number of publications in the field of medicine. However, there is no bibliometric analysis of the AI-assisted colonoscopy. It is of great importance to carry out a bibliometric analysis in this area, especially from the perspectives of countries, journals, authors, and keywords, giving readers a vivid overview of the most important works in the past two decades and providing guidance to scholars in this area to determine future research direction.2. Materials and methods 2.1 Data Source and SearchLiterature retrieval was collected from the Web of Science Core Collection (WoSCC) on February 16, 2022. All searches were completed within the same day to avoid the bias caused by the daily database updates. The search terms and searching formulas are shown in Supplementary Figure 1. The time interval was set from 2000 to 2021. Only original and review papers were included. The key words used, language of articles and the inclusion and exclusion criteria were only with English translation. After the primary data search, two researchers (Bing-Hong Chen and Hoi-Ioi Ng) screened all manuscripts individually to ensure that they were relevant to the subject of this study. In total, 460 papers (Figure S2) matched the retrieval criteria, including 350 articles and 110 reviews.2.2 Data AnalysisLiterature analysis is a tool for the research of published literature based on statistical and metrological analysis methods. Microsoft Excel 2019 was used to create a trend chart of changes in the volume of documents published each year and forecast the growth of publications in the following year, providing an intuitive development t rend in th i s f i e ld . In th i s paper, Ci teSpace 5.8.R3c visualization software [8,9] is used for
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 5bibliometric analysis and literature knowledge mapping. According to CiteSpace 5.8.R3c, we did not find the duplicates. CiteSpace could analyze the development dynamics of the research field, and explore the evolving trends and research hotspots of its topics. The quantitative analysis process of the role of AI in colonoscopy is shown in Figure 1. The literature database was imported into CiteSpace software for development analysis , scientif ic research strength analysis, research highlights and topics analysis, and research frontier analysis. 3. Results3.1 Annual publicationsA total of 460 publications met the retrieval criteria, including 350 (76%) original articles and 110 (24%) rev iews . F igure 2 shows the chronological distribution of the publications from 2000 to 2021. As depicted in the diagram, the number of articles and reviews increased steadily from 2000 to 2018. Although the number of articles and reviews published was relatively small, a number of groundbreaking publicat ions were published, which laid the foundation for further research. From 2018 to 2021, the annual number of publications increased and peaked in 2021. The polynomial model was applied to forecast the growth of publications in the following year. The polynomial curve fitting of publication growth in this research showed a significant correlation (the coefficient of determination (R2) = 0.9928) between publicat ion year and number of publicat ions. Through curve fitting, the number of publications was estimated to reach 300 in 2022. 3.2 Analysis of journalsThese articles on the role of AI in colonoscopy were published in 200 journals. Gastrointestinal Endoscopy ranked first in the number of published articles (27). It is a professional journal designed to report investigations and observations relating to endoscopic procedures used in the study and treatment of digestive diseases. The World Journal of Gastroenterology (15) and Digestive Diseases and Sciences (14) followed in second and third place, respectively (Table 1). The 10 most co-cited journals and their impact factors (IFs) are given in Table 1. The 10 most co-cited journals almost had IFs (2020) higher than 10. More than half of the journals are influential in the field of endoscopy, meaning that AI-assisted colonoscopy research is a research hotspot at present. According to Table 1, we have found that the overlap rate between journals and co-cited journals is low, which indicates that prolific journals do not necessarily have a record of high citations. This indicates that while these Journals pays attention to the number of publications, the quality and innovation of the papers also need attention.Figure 3 is the dual map of subject fields, showing the relationship between citing journals and cited journals. It could be seen that there were mainly two citation paths, and the citing papers are mainly concentrated in two fields: (1) medicine, medical, clinical and (2) molecular biology, and immunology. While the cited papers were mainly located in three fields: (1) health, nursing, and medicine, (2) molecular biology and genetics, and (3) dermatology, dentistry, and surgery.3 .3 Di s tr ibut ion o f countr i e s / reg ions and institutesThe papers in AI and colonoscopy research were contributed by 60 countries/regions. The top 10 contributors are presented in Table 2. Extensive collaborations were observed among countries/regions (Figure 4A). Citespace marks important nodes with purple circles, which is an index to measure the importance of nodes in the network. The United States is not only the highest contributor but also a central collaborator with other countries, as indicated by its highest centrality value. China, the unique developing country, ranks second among the top 10 countries/regions. Most of the top 10 countries are developed countries, which shows that the development of national economic strength is a prerequisite for scientific progress.
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal6A total of 316 institutions have contributed to this area (Figure 4B). Table 2 shows the 10 most productive institutions, contributing more than 20% of total publications (The count can add up to more than the total number of results, as one work might have more than one author). On the list, the most productive institutions are Showa University and the University of Oslo with 21 publications, respectively. Harvard Medical School ranked second (18 publications). There are purple circles in the outermost layer of some nodes, which represent the node centrality. The Mayo Clinic and the University of California in Los Angeles, USA, have strong centrality, which means that they play an important role in inter-institutional coopera t ion and in format ion exchange . The distribution of institutions is basically the same as that of countries. Similar to collaboration between countries, the collaboration between institutions was also important. Even though there are a large number of publ icat ions in var ious countr ies , their international influence is limited, indicating that although countries around the world have been conducting relevant research in AI-assisted colonoscopy in the past two decades, there is still a need for broader cooperation and higher-quality research to promote the development of this field.3.4 Analysis of authorsMore than 440 authors contributed to this field of research. Among the top 10 contributing authors (Table 3), Yuichi Mori (19 publications) was ranked first. More than half of the top 10 authors are from Japan, which is related to Japan’s leading research and technology in the field of digestive endoscopy. The top 10 co-cited authors are listed in Table 3, and the author’s co-cited network analysis is visualized in Figure 5. A co-citation relationship among authors is established when two (or more) authors are cited in one or more subsequent papers at the same time. We can obtain a clear picture of core authors and their contributions to a certain field by analyzing the authors’ co-cited networks, the strength of which indicates the degree of participation of the authors. The most frequently co-cited author is Douglas K. Rex (123 citations) from the USA. Right after, Pu Wang appears with 112 citations, the only person from China in the top 10 co-cited authors. However, only two of the top 10 active authors are the top 10 co-cited authors, suggesting that prolific authors do not necessarily have a record of high citation, which is a more effective indicator of academic influence. The low overall quality of papers and insufficient innovation are still the primary problems plaguing the development of scientific research around the world.3.5 Analysis of reference co-citationCo-citation analysis can reveal research trends in AI-assisted colonoscopy. The 460 bibliographic recordings from 2000 to 2021 were visualized, and a year time slice was selected for analysis. CiteSpace 5.8.R3c was used to construct a network of co-cited references (Figure 6A) that revealed the relevance between papers. We present the 10 most cited references in Table 4. They come from different countries, and there are multiple collaborators in the same paper from different countries, which indicates that experts have carried out extensive exchanges and cooperation with scholars from all over the world. An article published by Gregor Urban et al. in 2018 ranks first with 87 citations [10], reporting designed and trained state-of-the-art deep convolutional neural networks (CNN) to detect polyps in real-time conditions using a massive, diverse, and representative set of hand-labeled images from screening colonoscopies collected from over 2000 patients for the first time with an accuracy of 96.4%. However, it still requires validation in large, multi-center trials. Wang P et al. (2019), the second most cited article [11], used a high-performance computer-aided diagnosis (CADe) system based on deep learning and found that the CADe system could increase the polyp detection rate and adenoma detection rate from 29% and 20% to 45% and 29%, respectively. This effect was mainly due to the higher rate of small adenomas
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 7found, and the detect ion rate of hyperplast ic polyps was also significantly increased. This is the first prospective randomized controlled trial in this field. Interestingly, nine out of the first ten cited studies focused exclusively on AI-assisted colonoscopy for polyps. ADR has become the focus in this area, but evidence on the ability to increase detection during real-time clinical practice is scarce to date. Fortunately, with the development of AI, the effectiveness of CADe system in real clinical practice has been shown according to in-human clinical testing [12]. Accordingly, AI-assisted colonoscopy still has broad research prospects waiting for discovery.3.6 Cluster interpretationsOn the basis of the co-cited references, we further constructed a network map to visualize the key clusters of co-cited references. If two publications have many common references, they are inclined to be homogenous [13]. Based on this logic, we divided articles into several clusters and the five biggest clustering results are shown in Figure 6B. Modularity (Q-score) and Silhouette (S-score) evaluate the cluster mapping. Q > 0.3 means the structure of the delineated associations is significant. S > 0.5 means that the cluster is reasonable, and S > 0.7 indicates that the cluster is efficient and convincing. Our Q value and S value are 0.8342 and 0.9333, respectively. Cluster #0, namely artificial intelligence, was the largest cluster, consisting of 93 references, followed by polyp detection (cluster #1), water exchange (cluster #2), colorectal cancer (cluster #3), and deep learning (cluster #4). Cluster #1, #3 and #4 are currently the latest research hotspots, suggesting that more and more researchers are paying attention to the application of deep learning in colonoscopy.A timeline view of co-cited references shows how research hotspots changed over time (Figure 7). Figure 7 displays a timeline visualization of distinct co-citations and shows that Cluster #0 (artificial intelligence) and Cluster #1 (polyp detection) contain a large number of nodes with red rings scattered along the timeline for nearly a decade, indicating that they are the latest research hotspots that are worthy of attention. Cluster #2 (water exchange) is a summary of the references related to AI-assisted colonoscopy and water exchange. The timeline view shows a slight decrease in the number of publications of studies on water exchange and AI-assisted detection of polyps in recent years. The analysis results are consistent with the actual research. The colonoscopy CADe system is the most concerned and in-depth research direction of AI in the field of colonoscopy. Current research mainly focuses on the automatic detection of colon polyps and the real-time identification of polyp nature, but most of the studies are still in the preclinical exploratory stage. Furthermore, large-scale and worldwide multi-center clinical applications are still limited [14].3.7 Analysis of keywordsOver 400 keywords were detected according to the keyword co-occurrence analysis (Figure 8). The top seven high-frequency keywords were colorectal cancer, co lonoscopy, a r t i f i c ia l in te l l igence , classification, deep learning, validation, and cancer (Table 5). Keywords with high frequency could be treated as indicators of hotspots in a certain research field [9].The keywords with strong occurrence bursts were explored, and 20 keywords with the strongest citation bursts were identified (Figure 8). The appearance times and periods of the burst keywords varied. Keywords with high sudden occurrence intensity are emerging hotspots in the research f ield. The longest burst durat ion occurred in virtual colonoscopy (with a burst strength of 2.74), which started in 2000 and ended in 2015. Virtual colonoscopy (VC), also referred to as computed tomographic colonography (CTC), can give an intraluminal visualization of the colon that is similar to endoscopy. In the past three years, the emergence of burst keywords like convolutional neural networks (CNN), inflammatory bowel disease (IBD), and computer-aided diagnosis (CAD) indicates research
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal8on the role of AI in colonoscopy has begun to become a hot spot. In this deep learning revolution, CNN is the main force driving all these outbreaks and plays a very important role in the current development of AI. The keywords burst detection identified IBD as a hot topic from 2019 to 2021, and researchers in this area have given increasing attention to AI-assisted identification of IBD. Keywords can represent areas of focus in a given field, providing guidance for future research.Table 1. Top 10 Journals and co-cited Journals.Rank Journals Country Count IFs 2020 Co-cited Journals Country Count IFs 20201 Gastrointestinal EndoscopyThe United States 27 9.427 Gastroenterology The United States 290 22.6822 World Journal of Gastroenterology China 15 5.742 Gastrointestinal EndoscopyThe United States 280 9.4273Digestive Diseases and SciencesThe United States 14 3.199 Endoscopy Germany 242 10.0934Endoscopy International OpenGermany 13 None Gut England 238 23.0595 Digestive Endoscopy Australia 11 7.559 American Journal of Gastroenterology Germany 217 10.8646 Ieee Access The United States 10 3.367 New England Journal of MedicineThe United States 211 91.2457 Endoscopy Germany 9 10.093Clinical Gastroenterology and HepatologyEngland 161 11.3828Ieee Transactions on Medical ImagingThe United States 8 10.048 Ieee Transactions on Medical ImagingThe United States 153 10.0489 Medical Image Analysis Netherlands 8 8.545 CA-A Cancer Journal for CliniciansThe United States 129 508.70210 Plos One The United States 8 3.24 Annals of Internal MedicineThe United States 118 25.391
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 9Table 2. Top 10 productive countries/regions and Institutes.Rank Country/Region Count Institute Count1 The United States 159 Showa University (Japan) 212 China 89 University of Oslo (Norway) 213 Japan 49 Harvard Medical School (The United States) 184 Italy 39 University of California Los Angeles (The United States) 165 South Korea 33 Nagoya University (Japan) 166 England 32 National Cancer Center (Japan) 147 Germany 27 Mayo Clinic (The United States) 128 Norway 27 Humanitas University (Italy) 119 Taiwan 22 Oslo University Hospital (Norway) 910 Spain 19 Vet Affairs Greater Los Angeles Healthcare System (The United States) 8Table 3. The 10 most productive authors and the top 10 co-cited authors.Rank Authors Count Cited Authors Count1 Yuichi Mori (Japan) 19 Douglas K Rex (The United States) 1232 Masashi Misawa (Japan) 15 Pu Wang (China) 1123 Shin-Ei Kudo (Japan) 14 Jorge Bernal (Spain) 964 Kensaku Mori (Japan) 14 Yuichi Mori (Japan) 965 Felix W Leung (The United States) 13 Michal F Kaminski (Norway) 896 Cesare Hassan (Italy) 12 Gregor Urban (The United States) 897 Alessandro Repici (Italy) 12 Michael F Byrne (Canada) 828 Hayato Itoh (Japan) 11 Masashi Misawa (Japan) 799 Yutaka Saito (Japan) 10 Nima Tajbakhsh (The United States) 7810 Tyler M Berzin (The United States) 10 Douglas A Corley (The United States) 77
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal10Table 4. Top 10 co-cited references.Rank Cited References Journal Author Year Count1 Deep Learning Localizes and Identifies Polyps in Real Time With 96% Accuracy in Screening ColonoscopyDOI 10.1053/j.gastro.2018.06.037Gastroenterology. Urban G, et al.2018 872 Real-time automatic detection system increases colonoscopic polyp and adenoma detection rates: a prospective randomised controlled studyDOI 10.1136/gutjnl-2018-317500Gut. Wang P, et al.2019 823 Adenoma Detection Rate and Risk of Colorectal Cancer and DeathDOI 10.1056/NEJMoa1309086The New England Journal of MedicineDouglas A Corley, et al.2014 764 Real-time differentiation of adenomatous and hyperplastic diminutive colorectal polyps during analysis of unaltered videos of standard colonoscopy using a deep learning modelDOI 10.1136/gutjnl-2017-314547Gut. Byrne MF, et al.2019 725 WM-DOVA maps for accurate polyp highlighting in colonoscopy: Validation vs. saliency maps from physiciansDOI 10.1016/j.compmedimag.2015.02.007Computerized medical imaging and graphics: the official journal of the Computerized Medical Imaging SocietyBernal J, et al.2015 666 Accurate Classification of Diminutive Colorectal Polyps Using Computer-Aided AnalysisDOI 10.1053/j.gastro.2017.10.010Gastroenterology Chen PJ, et al.2018 607 Automated Polyp Detection in Colonoscopy Videos Using Shape and Context InformationDOI 10.1109/TMI.2015.2487997IEEE transactions on medical imagingTajbakhsh N, et al.2016 598 Comparative Validation of Polyp Detection Methods in Video Colonoscopy: Results From the MICCAI 2015 Endoscopic Vision ChallengeDOI 10.1109/TMI.2017.2664042IEEE transactions on medical imagingBernal J, et al.2017 57
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 119 Real-Time Use of Artificial Intelligence in Identification of Diminutive Polyps During Colonoscopy: A Prospective StudyDOI 10.7326/M18-0249Annals of internal medicineMori Y, et al.2018 5610 Artificial Intelligence-Assisted Polyp Detection for Colonoscopy: Initial ExperienceDOI 10.1053/j.gastro.2018.04.003Gastroenterology Misawa M, et al.2018 54Table 5. The top 20 keywords with the highest frequency.Rank Keywords Count Rank Keywords Count1 Colorectal Cancer 113 11 Convolutional Neural Network 452 Colonoscopy 100 12 Lesion 393 Artificial Intelligence 94 13 Computer Aided Diagnosis 384 Classification 77 14 Polyp 325 Deep Learning 75 15 Polyp Detection 316 Validation 61 16 Machine Learning 297 Cancer 60 17 Adenoma Detection 268 Diagnosis 59 18 Miss Rate 259 Risk 57 19 Adenoma Detection Rate 2410 System 52 20 Computer Aided Detection 24Figure 1.Figure 1. Quantitative analysis process of the role of artificial intelligence in colonoscopy.
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal12Figure 2.Figure 2. Chronological distribution of publications in artificial intelligence in colonoscopy research from 2000 to 2021.Figure 3.Figure 3. A dual-map overlap of journals on AI-assisted colonoscopy research carried out by Citespace.
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 13Figure 4.Figure 4. CiteSpace network visual map of country/regions and institutions involved in AI-assisted colonoscopy research. (A) Collaboration analysis of countries/regions. (B) Collaboration analysis of institutions. Each circle represents a country/region/institutions. Size of circle is positively correlated with the number of articles published by country/region/institutions, and links between two circles represents a collaboration between two country/region/institutions on the same article. Line thickness is positively correlated with frequency of collaborations. Figure 5.Figure 5. CiteSpace network visualization map of co-cited authors of the articles related to AI-assisted colonoscopy research. The node size was positively associated with the cited counts of the authors, and the thickness of the lines between every two nodes represented the frequency of being co-cited between those two authors.
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal14Figure 6.Figure 6. Analysis of references in AI-assisted colonoscopy research. (A) Network map of co-cited references. Each circle represents a reference. Size of circle is positively correlated with frequency of citations, and links between two circles represent two references that were cited in the same article. (B) Clustered networks of co-citation status of the investigated 460 references via CiteSpace.Figure 7.Figure 7. Timeline view of co-cited references related to AI-assisted colonoscopy research. The bold timeline indicates that the clustering topic was a hotspot during this period. Citation tree-rings with different sizes on the timeline represent some key articles with a high citation frequency.
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 15Figure 8.Figure 8. (A) CiteSpace network visualization map of co-occurring keywords. (B)Top 20 burst keywords in articles related to AI-assisted colonoscopy research.4. DiscussionThis is the first bibliometric analysis of AI-assisted colonoscopy research that analyzed related research publications from multiple dimensions and showed a systematic view for understanding this field over the past 20 years. The United States, China, and Japan are the top three countries most interested in AI-assisted colonoscopy research. The United States is not only the most productive country in the field but also the country with the highest impact on published art icles . The top three most frui tful research institutions were located in Japan, Norway, and the United States. The two institutions that play a bridging role in the exchange of institutional collaboration are both from the United States. More than half of the highly cited journals are from the United States, reflecting the country’s leadership in AI-assisted colonoscopy research. Interestingly, nine out of the first ten cited studies focused exclusively on AI-assisted colonoscopy for polyps, in which ADR became the focus of the field. AI has been applied to the detection and recognition of polyps under colonoscopy and achieved certain results. Part of the research results have been applied to practical work. It can be seen from the cluster analysis map that AI has become a research hotspot in the field of colorectal polyp detection in recent years. However, the timeline view of references shows a slight decrease in the number of publications of studies on AI-assisted detection of polyps , wi th s tudies h i t t ing a bot t leneck. Perhaps the relevant studies are mostly limited to retrospective studies and cannot further demonstrate their effectiveness in real-world applications, or the clinical trial is still not finished yet [15], so further clinical validation in large-sample multi-center medical institutions is needed. The timeline view indicates that AI research will remain hot in the future, but it is no longer limited to the detection of polyps. Keyword burst detection indicates that AI research will focus more on the diagnosis and treatment of lower gastrointestinal lesions, indicating future research trends in this field.Compared with traditional reviews, CiteSpace-based analysis provides better insight into research focus and trends. The real-world research in AI-assisted colonoscopy has already been applied in clinical practice such as adenoma-discovery,
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal16co lonoscopy examina t ion t ime, examina t ion speed, and bowel preparation score. Now it is a vital moment since AI-assisted research hit the bottleneck, and it is also the main reason why we have to perform this bibliometric analysis. Wi t h t h e i m p r o v e m e n t o f a l g o r i t h m i c computing power, computer level, and the advent of the era of big data, AI technology has flourished and changed traditional medicine. AI-assisted colonoscopy research is in full swing and will play an epic and transformative role in the management of lower gastrointestinal tract lesions, bringing great convenience to clinical work. The findings from this bibliometric study provided insights into research trends on AI-assisted colonoscopy in the past two decades and hopefully will provide new examination and treatment ideas for colonoscopy.5. Author contributionsBH Chen, HI Ng, Y Ke, W Zhang, GQ Wang: conception, design and definition of intellectual content. BH Chen, HI Ng: collection of data and manuscript drafting. Y Ke, W Zhang, GQ Wang: manuscr ip t rev i s ing . BH Chen , HI Ng: da ta analysis and interpretation. W Zhang, GQ Wang: administrative support. The manuscript has been read and approved by all the authors.6. FundingThis work was supported by the Sanming project of Medicine in Shenzhen [Grant numbers SZSM201911008], CAMS Innovation Fund for Medical Sciences [Grant numbers 2021-1-I2M-061, 2021-1-I2M-010] and Beijing Hope Run Special Fund of Cancer Foundation of China [LC2022B35].7. Confl icts of interestThe authors report there are no competing interests to declare.8. References[1] Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. The New England journal of medicine . 2012 Feb 23;366(8):687-696, doi: 10.1056/NEJMoa1100370.[2] Zhao S, Wang S, Pan P, et al. Magnitude, Risk Factors, and Factors Associated With Adenoma Miss Rate of Tandem Colonoscopy: A Systematic Review and Meta-analysis. Gastroenterology. 2019 May;156(6):1661-1674.e1611, doi: 10.1053/j.gastro.2019.01.260.[3] Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. The New England journal of medicine. 2010 May 13;362(19):1795-1803, doi: 10.1056/NEJMoa0907667.[4] Sharma P, Gupta N, Kuipers EJ, Repici A, Wallace M. Advanced imaging in colonoscopy and its impact on quality. Gastrointestinal endoscopy. 2014 Jan;79(1):28-36, doi: 10.1016/j.gie.2013.08.020.[5] Antonelli G, Gkolfakis P, Tziatzios G, Papanikolaou IS, Triantafyllou K, Hassan C. Artificial intelligence-aided colonoscopy: Recent developments and future perspectives. World journal of gastroenterology. 2020 Dec 21;26(47):7436-7443, doi: 10.3748/wjg.v26.i47.7436.[6] Wang P, Liu P, Glissen Brown JR, et al. Lower Adenoma Miss Rate of Computer-Aided Detection-Assisted Colonoscopy vs Routine White-Light Colonoscopy in a Prospective Tandem Study. Gast roenterology. 2020 Oct;159(4):1252-1261.e1255, doi: 10.1053/j.gastro.2020.06.023.[7] Repici A, Badalamenti M, Maselli R, et al. Eff icacy of Real-Time Computer-Aided Detect ion of Colorecta l Neoplas ia in a Randomized Trial. Gastroenterology. 2020 Aug;159(2):512-520.e517, doi: 10.1053/j.gastro.2020.04.062.[8] Chen C , Dubin R , Kim MC. Emerg ing trends and new developments in regenerative medicine: a scientometric update (2000 - 2014) . Expe r t op in ion on b io log ica l therapy. 2014 Sep;14(9):1295-1317, doi: 10.1517/14712598.2014.920813.[9] Chen C. Searching for intellectual turning po in t s : p rogress ive knowledge domain visualization. Proceedings of the National
Global trends of artificial intelligence-assisted colonoscopy in the last 20 years: a bibliometric analysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 17Academy of Sciences of the United States of America. 2004 Apr 6;101 Suppl 1(Suppl 1):5303-5310, doi: 10.1073/pnas.0307513100.[10] Urban G, Tripathi P, Alkayali T, et al. Deep Learning Localizes and Identifies Polyps in Real Time With 96% Accuracy in Screening C o l o n o s c o p y. G a s t r o e n t e r o l o g y. 2 0 1 8 Oct;155(4):1069-1078.e1068, doi: 10.1053/j.gastro.2018.06.037.[11] Wang P, Berzin TM, Glissen Brown JR, et al. Real-time automatic detection system increases colonoscopic polyp and adenoma detection rates: a prospective randomised controlled study. Gut. 2019 Oct;68(10):1813-1819, doi: 10.1136/gutjnl-2018-317500.[12] Mori Y, Kudo SE, East JE, et al. Cost savings in colonoscopy with artificial intelligence-aided polyp diagnosis: an add-on analysis of a clinical trial (with video). Gastrointestinal endoscopy. 2020 Oct;92(4):905-911.e901, doi: 10.1016/j.gie.2020.03.3759.[13] Chen C, Song M. Visualizing a field of research: A methodology of systematic scientometric reviews. PloS one. 2019;14(10):e0223994, doi: 10.1371/journal.pone.0223994.[14] Kamitani Y, Nonaka K, Isomoto H. Current Status and Future Perspectives of Artificial Intelligence in Colonoscopy. Journal of clinical medicine. 2022 May 22;11(10)doi: 10.3390/jcm11102923.[15] He J, Baxter SL, Xu J, Xu J, Zhou X, Zhang K. The practical implementation of artificial intelligence technologies in medicine. Nature medicine. 2019 Jan;25(1):30-36, doi: 10.1038/s41591-018-0307-0.[16] Yan WT, Lu S, Yang YD, et al. Research trends, hot spots and prospects for necroptosis i n t h e f i e l d o f n e u r o s c i e n c e . N e u r a l regeneration research. 2021 Aug;16(8):1628-1637, doi: 10.4103/1673-5374.303032.
Lai Si KONG et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal18血液透析患者高磷血症與治療依從性的相關性研究Relative study of hyperphosphatemia and treatment adherence of patients undergoing hemodialysis摘要目的：調查血液透析患者高磷血症及治療依從性的現狀。方法：採用便利取樣法，於2019年7月─2019年12月間選取108名血透患者作為研究對象。採用自行設計的一般資料調查表及《終末期腎病維持性血液透析患者治療依從性量表》進行問卷調查。應用SPSS 21.0統計軟件進行資料分析。 結果：治療依從性以及飲食依從性、液體攝入依從性、藥物依從性和透析方案依從性的得分與血磷值呈負性相關，相關係數分別為-0.782、-0.583、-0.460、-0.622、-0.371 (p<0.01)。結論：血透患者血磷控制不理想，治療依從性整體評價一般，而治療依從性表現越差，血磷水平越高；反映需要加強用藥指導、強化飲食和液體限制的依從行為。關鍵詞：血液透析；高磷血症；治療依從性AbstractObjective: This study was conducted to explore the relationship between hemodialysis patients’ hyperphosphatemia and their adherence to treatment. Methods: Convenience sampling was used to select 108 hemodialysis patients from one association for renal failure patients between July 2019 and December 2019. A general personal information form and the Medical Treatment Adherence Scale for End-Stage Renal Disease Patients with Maintenance Hemodialysis were used to collect data. Statistical analysis was conducted using SPSS version 21.0. Result: In correlation analysis, serum phosphate levels were negatively correlated with adherence to treatment, including diet, fluid restriction, medication, and dialysis. Resulting correlation coefficients (r) were -0.782, -0.583, -0.460, -0.622, -0.371 (p<0.01). Conclusion: Patients with hemodialysis had unsatisfactory phosphate control, and treatment adherence was generally acceptable. Those with poor treatment adherence had a higher serum phosphate level. It is necessary to strengthen medication guidance, as well as to improve compliance with diet and fluid restrictions. Keywords: Hemodialysis; Hyperphosphatemia; Treatment Adherence1仁伯��合��─血��析�2中�大學�理學�3�門���理學�*Correspondence to: Lai Si KONG, konglaisi@gmail.com江麗詩 1*，劉可 2，歐妙玲 3Lai Si KONG1*, Ke LIU2, Mio Leng AU3
Relative study of hyperphosphatemia and treatment adherence of patients undergoing hemodialysis第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 23要症狀為皮膚搔癢，其次為骨關節疼痛。雖然本研究結果與上海市 [8]及台灣地區 [9]的研究報導一致，臨床症狀與治療依從性無關，但持續搔癢和疼痛對患者來說是一件非常困擾的事，護理人員應關注患者的心理狀況，避免負性情緒影響心理素質，降低治療依從性 [10]。本研究結果發現血透患者透析方案依從性最好，其次為藥物依從性，飲食依從性一般，液體攝入依從性最差；可見在醫護人員主導的範疇，患者的依從表現較好，需要患者自我約束的範疇，依從行為有待加強。本研究結果顯示治療依從性總平均分為 3.67±0.44分，與採用相同量表作研究工具的重慶 [11]及廣州 [12]地區研究結果相近，表現不依從的情況較國外的研究結果略高 [13]，說明生活文化相近的地區，血透患者依從性的狀況亦大致相同。血液透析齡超過 5年的血透患者在藥物依從表現較理想，與其他的研究報導相似 [14]，血透時間越長，對疾病和治療的認知更充分，治療依從性越好；有研究則報導血液透析時間多於 5年的患者對健康和治療失去信心，治療依從性較差 [12,15]。即使患者對疾病認知良好，但負性情緒對透析患者的治療依從表現也有影響，提示護理人員應對血透患者的心理狀況加強關注及干預，提高患者心理素質，促進患者積極面對疾病和治療 [10]。藥物相關因素對不同維度依從性的差異有顯著關係，與澳洲 [16]和美國 [15]的研究報導相似；血透患者對藥物的認知、降磷藥物的使用方法、藥物的經濟負擔、每天的藥物數量均與藥物依從性有關。複雜的藥物處方是影響患者正確使用藥物的重要因素，反映了患者對簡潔明瞭的藥物說明或藥物指導有很大需求。血透患者對服從處方的態度和意願會影響依從行為表現，提示積極正向的情緒對血液透析患者的治療依從性有影響，臨床上血透患者的心理狀況關注及干預是必要的。血透患者血磷控制不理想，血透患者自評的治療依從性整體評價一般，治療依從性越差，血磷水平越高。研究 [9,17]指出加強血透患者的健康教育，可以提升其依從行為；以患者為主導，一對一的授權教育方式能有效提升患者疾病相關知識、自我管理動機及健康促進行為 [18]。在血透護理的實務工作中，健康教育是一個系統性的護理行為，護理人員應根據患者健康狀況及生活習慣等協助患者製訂個性化的疾病管理方案，從而改善飲食和服藥習慣，達至有效調控血磷，改善疾病預後並提升生活品質。本研究在治療依從性的評價上，只採用了主觀評價的方式，可能存在偏倚。回顧性血磷值只收集了 6個月的數據，未包含年度所有節慶，血磷水平的分析方面存在一定的局限。本研究納入了個人資料及臨床資料等影響因素，但解釋變異度較低，血液透析患者治療依從性的影響因素仍需進一步深入研究。5. 參考資料[1] Moe SM. Calcium as a cardiovascular toxin in CKD-MBD. Bone, 2017 Jul;100: 94-99. doi: 10.1016/j.bone.2016.08.022.[2] Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol. 2001 Oct;12(10):2131-2138. doi: 10.1681/ASN.V12102131. [3] K i d n e y D i s e a s e : I m p r o v i n g G l o b a l Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Gu ide l i ne Upda t e f o r t he D iagnos i s , Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.[4] 張艷, 黃金. 終末期腎病維持性血液透析患者治療依從性量表的編制[J]. 中國全科醫學,2013,16(28):3312-3316.DOI:10.3969/j.issn.1007-9572.2013.28.010.
血��析�者��血���療�從性�相�性研�澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal24[5] Nat ional Kidney Foundat ion. K/DOQI c l i n i ca l p r ac t i c e gu ide l i ne s fo r bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003 Oct;42(4 Suppl 3):S1-201. [6] Arbor Research Collaborative for Health. US-DOPPs Practice Monitor, October 2019[2020-3-17]. https://www.dopps.org/DPM/default.aspx[7] 趙德龍 . 維持性血液透析患者流行病學調查及生存預後相關性分析[D]. 中國人民解放軍總醫院,2016.[8] L indberg M, Lindberg P. Overcoming obs tac les fo r adherence to phospha te binding medication in dialysis patients: a qualitative study. Pharm World Sci. 2008 Oct;30(5):571-6. doi: 10.1007/s11096-008-9212-9. [9] 何雅芳,楊慕慈, 陳金順, 等. 長期血液透析病患血磷控制遵從行為相關因素之研究. 臺灣腎臟護理學會雜誌. 2015, 14(1): 1-18.doi: 10.3966/172674042015031401001.[10] 陳雪玲,護理干預對尿毒癥血液透析患者心理的影響 [ J ] . 護士進修雜志 , 2012 ,27 (9 ) :837 -839 .DOI :10 .3969 /j.issn.1002-6975.2012.09.032. [11] 雷延蘭 , 羅玲 , 陳莉 , 等 . 協同護理模式對血液透析患者自我護理能力和透析治療依從性的影響 [ J ] . 中國血液凈化 , 2 0 1 6 , 1 5 ( 1 ) : 5 8 - 6 2 . D O I : 1 0 . 3 9 6 9 /j.issn.1671-4091.2016.01.016.[12] 翁慧雯,張國娟 , 藍玉泓 , 等 . 健康素養、特質應對方式對血液透析患者治療依從性的影響 [ J ] . 中國中西醫結合腎病雜志 ,2019,20(3):235-237.DOI:10.3969/j.issn.1009-587X.2019.03.014. [13] Naalweh KS, Barakat MA, Sweileh MW, Al-Jabi SW, Swei leh WM, Zyoud SH. Treatment adherence and perception in patients on maintenance hemodialysis: a cross - sectional study from Palestine. BMC Nephrol . 2017 May 30;18(1):178. doi: 10.1186/s12882-017-0598-2.[14] A l S a l m i I , L a r k i n a M , Wa n g M , Subramanian L, Morgenstern H, Jacobson SH, Hakim R, Tentori F, Saran R, Akiba T, Tomilina NA, Port FK, Robinson BM, Pisoni RL. Missed Hemodialysis Treatments : International Variation, Predictors, and Outcomes in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2018 Nov;72(5):634-643. doi: 10.1053/j.ajkd.2018.04.019.[15] Umeukeje EM, Mixon AS, Cavanaugh K L . P h o s p h a t e - c o n t r o l a d h e r e n c e i n hemodialysis patients: current perspectives. P a t i e n t P r e f e r A d h e r e n c e . 2 0 1 8 J u l 4 ; 1 2 : 11 7 5 - 11 9 1 . d o i : 1 0 . 2 1 4 7 / P PA .S145648.[16] Ghimire S, Castelino RL, Lioufas NM, Peterson GM, Zaidi ST. Nonadherence to Medication Therapy in Haemodialysis Patients: A Systematic Review. PLoS One. 2015 Dec 4;10(12):e0144119. doi: 10.1371/journal.pone.0144119. [17] 石梅,曹曉翼, 張穎君, 等. 維持性血液透析患者治療依從行為與治療態度的關系研究[J]. 重慶醫學,2017,46(27):3856-3858.DOI:10.3969/j.issn.1671-8348.2017.27.036. [18] 葉淑敏 , 林育如 , 吳莒瑛 , 等 . 血液透析護理人員執行高血磷護理指導完整性之改善方案 . 領導護理 , 2018, 19(1): 91-104. DOI:10.29494/LN.201803_19(1).0008.
Jin Wen ZHANG et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 2539 例成人住院艱難擬梭菌感染相關性腹瀉的臨床特徵分析Clinical characteristics of Clostridioides difficile-associated diarrhea: analysis of 39 adult inpatients 張進文，朱雪茵，余漢濠 *Jin Wen ZHANG, Xue Yin ZHU, Hon Ho YU*摘要 目的：了解目前澳門鏡湖醫院的成人艱難擬梭菌感染相關性腹瀉（CDAD）流行情況、臨床特徵、危險因素及診治現狀，為臨床防治提供依據。方法：回顧性分析2017年7月1日至2022年6月30日期間澳門鏡湖醫院CDAD成人住院患者的一般情況及臨床特點。 結果：共39例CDAD患者，檢出率為同期住院患者的萬分之3.6；老齡患者佔79.3%，超過九成患者有基礎疾患，近90%的患者有抗生素使用史，近7成患者有質子泵抑制劑使用史；治療方案多採用Metronidazole或Vancomycin，76.9%患者治療當天症狀有明顯改善。 結論：老齡、具基礎疾病、有抗生素或質子泵抑制劑使用史均為CDAD的高危因素；對高危腹瀉患者艱難擬梭菌檢測的重視以及對抗生素和質子泵抑制劑的合理使用，有利於CDAD的防治。關鍵詞：�����；��；老�；�生�AbstractObjective: To investigate the incidence, clinical characteristics and risk factors for Clostridioides difficile-associated diarrhea (CDAD) in adult inpatients in Kiang Wu Hospital to provide the basis for clinical prevention and treatment.Methods: The retrospective survey was conducted to analyse the general condition and clinical characteristics in adult inpatients in Kiang Wu Hospital between 2017/7/1 and 2022/6/30.Result: 39 cases was diagnosed CDAD with the detection rate of 0.036%. Elderly patients accounted for 79.3%. More than 90% cases had underlying diseases, approximately 90% cases with a history of antibiotic use and nearly 70% cases had a history of proton pump inhibitor (PPI) use. Metronidazole and Vancomycin were the most frequently used antibiotics. Symptoms improved significantly in 76.9% patients on the day of treatment. Conclusion: older age, underlying diseases and a history of the use of antibiotics or PPI are high-risk factors for CDAD. Awareness of Clostridioides difficile infection in high-risk diarrhea patients and reasonable use of antibiotics helps in the prevention and treatment of CDAD.Keywords: Clostridioides difficile; diarrhea; older age; antibioticsKiang Wu Hospital, Department of Gastroenterology*Correspondence to: Hon Ho YU, yuhonho@gmail.com
39例成人住��������相�性���臨����析澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal30床重視。與此同時，艱難擬梭菌感染作為一種傳染性疾病，有院內感染甚至爆發的風險 [7]。此外，艱難擬梭菌的芽孢對酒精不敏感 , 需用含氯的消毒劑或肥皂潔手，以及用含氯的消毒劑或其他殺芽孢製劑消毒環境，才能預防艱難擬梭菌的傳播。因為艱難擬梭菌存在人傳人的風險，醫護人員在接觸艱難擬梭菌患者時應注意穿防護服、戴手套以避免接觸傳播。適當的清潔消毒措施和必要的隔離，都是預防艱難擬梭菌院內傳播的重要措施 [19]。4. 參考文獻[1] Col l ins DA, Marce l l a S , Campbe l l M, Riley TV. Linkage study of surveillance and hospital admission data to investigate Clostridium difficile infection in hospital p a t i e n t s i n P e r t h , We s t e r n A u s t r a l i a . Anaerobe. 2022;74:102528.[2] Lim PL, Barkham TMS, Ling LM, Dimatatac F, Alfred T, Ang B. Increasing Incidence of Clostridium difficile-associated Disease, Singapore. Emerg Infect Dis J. 2008;14:1487-9.[3] Solanki D, Kichloo A, El-Amir Z, Dahiya DS, Singh J, Wani F, et al . Clostridium difficile Infection Hospitalizations in the Uni ted S ta tes : Ins igh ts From the 2017 National Inpatient Sample. Gastroenterol Res 2021;14:87-95. [4] Lee HS, Plechot K, Gohil S, Le J. Clostridium difficile: Diagnosis and the Consequence of Over Diagnosis. Infect Dis Ther. 2021;14:87-95.[5] Clancy CJ, Buehr le D, Vu M, Wagener M M , N g u y e n M H . I m p a c t o f R e v i s e d Infect ious Diseases Society of America and Society for Healthcare Epidemiology of America Clinical Practice Guidelines on the Treatment of Clostridium difficile Infections in the United States. Clin Infect Dis. 2013;108:478-98.[6] Kunishima H, Ohge H, Suzuki H, Nakamura A, Matsumoto K, Mikamo H, et al. Japanese Clinical Practice Guidelines for Management of Clostridioides (Clostridium) difficile infection. J Infect Chemother. 2022;28:1045–83.[7] 程敬伟, 刘文恩, 马小军, 等. 中国成人艰难梭菌感染诊断和治疗专家共识[J]. 协和医学杂志，2017,8:131-136.[8] Crobach MJT, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, et al. European Soc i e ty o f C l in i ca l Mic rob io logy and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Eur Soc Clin Microbiol Infect Dis Update Diagn Guid Doc Infect. 2016;22:S63–81.[9] Czepiel J, Dróżdż M, Pituch H, Kuijper E J , P e r u c k i W, M i e l i m o n k a A , e t a l . Clostr idium diff ic i le infect ion: review. E u r J C l i n M i c r o b i o l I n f e c t D i s . 2019;38:1211–21.[10] Guh AY, Kutty PK. Clostridioides difficile Infection. Ann Intern Med. 2018;169:ITC49–64.[11] Su rawicz CM, Brand t LJ , B in ion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for Diagnosis, Treatment, and Prevent ion of Clostr idium diff ic i le Infections. Off J Am Coll Gastroenterol ACG. 2013;108.[12] W i l c o x M H , F r e e m a n J , F a w l e y W, MacKinlay S, Brown A, Donaldson K, et al. Long-term surveillance of cefotaxime and piperacillin–tazobactam prescribing and incidence of Clostridium difficile diarrhoea. J Antimicrob Chemother. 2004;54:168–72.[13] Johnson S, Samore MH, Farrow KA, Killgore GE, Tenover FC, Lyras D, et al. Epidemics of Diarrhea Caused by a Clindamycin-Resistant S t ra in of Clos t r id ium di ff ic i le in Four Hospitals. N Engl J Med. 1999;341:1645–51.[14] Hensgens MPM, Goorhu i s A , Dekker s OM, Kuijper EJ. Time interval of increased r i sk for Clos t r id ium di ff ic i le infec t ion after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742–8.[15] Valiquette L, Cossette B, Garant M-P, Diab H, Pépin J. Impact of a Reduction in the Use of High-Risk Antibiotics on the Course of an Epidemic of Clostridium difficile-Associated D i s e a s e C a u s e d b y t h e H y p e r v i r u l e n t NAP1/027 Strain. Clin Infect Dis. 2007;45 Supplement_2:S112–21.[16] McDonald LC, Gerding DN, Johnson S,
Clinical characteristics of Clostridioides difficile-associated diarrhea: analysis of 39 adult inpatients 第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 31Bakken JS, Carroll KC, Coffin SE, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:e1–48.[17] Wetzel Daniela, McBride Shonna M. The Impact of pH on Clostridioides difficile Sporulation and Physiology. Appl Environ Microbiol. 2020;86:e02706-19.[18] Tawam D, Baladi M, Jungsuwadee P, Earl G, Han J. The Positive Association between Proton Pump Inhibitors and Clostridium Difficile Infection. Innov Pharm. 2021;12:21.[19] 姜春燕 , 李敏 , 谭漫红 . 艰难梭菌感染的现状和防控策略 . 世界华人消化杂志 2010 ; 18(34): 3667-3671
Xiao Wen DENG et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal32基於 PI-RADSV2.1 對比雙參數與多參數MRI 在前列腺癌的診斷價值Diagnostic value of biparametric MRI and multiparametric MRI based on PI-RADS V2.1 in prostate cancer1Department of Diagnostic Imaging Center, Kiang Wu Hospital, Macau2Department of Pathology, Kiang Wu Hospital, Macau*Correspondence to: Xue Bin XIE, xiexuebin@kwh.org.mo鄧小雯 1， 馬春林 1 ，伍玲 1，彭靜嫻 1 ，戴慧明 2，謝學斌 1*Xiao Wen DENG1, Chun Lin MA1, Ling WU1, Ching Han PANG1, Wai Meng TAI2, Xue Bin XIE1*摘要目的：基於第2.1版前列腺影像報告數據系統（PI-RADS V2.1），對比雙參數與多參數MRI對前列腺癌（PCa）的診斷價值。 方法：選取2019年1月至2022年12月鏡湖醫院收治的116例臨床需要排除 PCa進行MRI檢查的患者，掃描序列包括T2加權成像（T2WI）、擴散加權成像（DWI）及動態對比增強成像（DCE），以前列腺活檢或前列腺根治術病理結果和/或超過二年隨訪確診作爲診斷標準。兩名高年資放射科醫師基於PI-RADS V2.1分別對雙參數MRI（bpMRI）及多參數（mpMRI）方案的診斷效能進行評估，計算兩種方案的敏感度、特異度、準確度、陽性預測值、陰性預測值。結果：116例患者中，前列腺良性病變65例，PCa 51例，其中36例位於外周帶，15例位於移行帶。bpMRI檢測PCa的敏感度、特異度、準確度、陽性預測值、陰性預測值、AUC分別為66.67%、96.92%、83.62%、94.44%、78.7%、0.818， mpMRI為74.51%、87.69%、81.90%、82.61%、81.43%、0.811。 兩種方案的敏感度、特異度、準確度差異均無統計學意義（P＞0.05）。結論：bpMRI方案與常規 mpMRI 方案相比，具有相似的診斷準確性。選擇bpMRI作為PSA升高的患者進一步篩查臨床顯著癌的檢查手段是可行的。關鍵詞：第 2.1 版前列腺影像報告數據系統；雙參數磁共振成像；多參數磁共振成像；前列腺癌Abstract Objective: To diagnostic value of biparametric MRI and multiparametric MRI based on PI-RADS V2.1 in Prostate Cancer. Methods: A total of 116 untreated patients with clinically suspected PCa were examined for MRI in the KiangWu Hospital from Jan.2019 to Dec.2022, including T2 weighted imaging（T2WI）, diffusion weighted imaging （DWI）, and dynamic contrast enhanced MRI （DCE-MRI）, and then the prostate biopsy or radical prostatectomy was performed to determine the pathological results, or a≥2 years imaging follow-up. Two radiologists evaluated the diagnostic performance of the bpMRI and mpMRI schemes based on PI-RADS V2.1.
Diagnostic value of biparametric MRI and multiparametric MRI based on PI-RADS V2.1 in prostate cancer第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 33Results: Pathology confirmed 51 cases of prostate tumor, of which 36 were located in the peripheral zone and 15 in the transitional zone. The diagnostic sensitivity, specificity, accuracy, positive predictive value, negative predictive value of bpMRI were 66.67%, 96.92%, 83.62%, 94.44%, 78.75%, 0.818 respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, negative predictive value of mpMRI were 74.51%, 87.69%, 81.90%, 82.6%, 81.43%, 0.811 respectively. There was no statistically significant difference in sensitivity, specificity, and accuracy between the two schemes (P>0.05).Conclusion: Compared with the conventional mpMRI scheme, the bpMRI scheme has similar diagnostic accuracy. It is feasible to select bpMRI as a further screening method for clinically significant cancer in men with elevated PSA.Keywords: PI-RADS V2.1; bpMRI; mpMRI; Prostate cancer前列腺癌（prostate cancer，PCa）是老年男性常見疾病，根據世界衛生組織下屬國際癌症研究機構(IARC)的有關資料，2020年癌症發病率排名前四位分別是：乳腺癌（11.7%）、肺癌（11.4%）、結直腸癌（10.0%）和前列腺癌（7.3%）[1]。澳門癌症登記年報（2022）報導，癌症發病率排名前四位分別是肺癌（16%）、結直腸癌（14%）、乳腺癌（12%）和前列腺癌（7%）[2]，與WHO的資料相近。儘管前列腺特異性抗原 (PSA，prostate specific antigen)作為一種廣泛使用的生物標誌物，但是對前列腺癌的特異性和陽性預測值均較低，作爲篩選工具的作用尚存在爭議 [3]。在過去的幾十年中，多參數磁共振成像（multi-parametric magnetic resonance imaging，mpMRI）包括 T2加權成像（T2-weighted imaging，T2WI）、擴散加權成像（DWI，Diffusion-weighted imaging）和 動 態 對 比 增 強（dynamic contrast enhanced，DCE）研究，逐漸成為檢測前列腺癌的標準，並通過針對可疑病變提高活檢率，最大限度地降低臨床上非顯著前列腺癌的漏診風險。為了規範前列腺 MRI 的圖像解釋和報告模式，指導臨床醫師對前列腺疾病的診斷，2012年歐洲泌尿生殖放射學會發佈了前列腺影像報告數據系統（prostate imaging reporting and date system，PI-RADS V1）[4]。 通 過 對 2012 版 PI-RADS及北美放射學年會 2014年版的補充、刪減和更新，2019年又發佈了 PI-RADS V2.1[5]。根據PI RADS v2.1，前列腺MRI檢查應包括DCE序列，但是對比劑在檢查中的使用還存在爭議 [6]。釓造影劑 (GBCA) 可能沉積在大腦和其它組織中，這種情況甚至出現在腎功能正常的個體中。而 DCE僅在 DWI不確定時對外周帶 (PZ)病變產生影響，對於移行區 (TZ) 的評估沒有公認的作用。另一方面，前列腺 mpMRI價格昂貴、耗費時間，難以滿足日益增長的前列腺 MRI 需求。近年來非增強 MRI，即 T2WI 聯合 DWI 的 bpMRI檢查方案，已被提議作為 mpMRI 的替代方案 [7-8]。本 研 究 主 要 對 比 PI-RADS V2.1bpMRI 和mpMRI方案對 PCa的診斷價值，旨在瞭解兩者對於診斷前列腺癌的一致性情況，以探討減少造影劑使用的可能性，從而縮短掃描時間。1. 資料與方法1.1 臨床資料回顧性收集本院 2019-2022年經病理證實的PCa和 /或超過二年隨訪確診良性結節共 116例，年齡 53-81歲，中位年齡 66.6歲。所有患者均進行血清 PSA評估、直腸指檢，並在 3.0 T或 1.5T MRI 儀獲取圖像數據。所有患者在 MRI檢查後的1個月內行超聲引導下經直腸 8-12針系統穿刺活檢術、前列腺癌根治術或超過 2年隨訪復查，以前列腺各分區的穿刺病理結果作為診斷金標準。剔除了以下情況：檢查前曾做前列腺穿刺，MRI採集不完整，有鄰近結構侵犯、淋巴結或骨轉移的前列腺癌，病理結果不明確；患者不配合致運
基� PI-RADSV2.1對��參數�多參數 MRI��列�����價值澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal34動偽影明顯導致圖像欠佳影響診斷。Gleason 評分 (GS) ≥ 6（3+3） 定義為陽性。1.2 儀器與方法 MRI 使用 PHILIPS 3.0T 或 GE 1.5T 磁共振成像設備，體部綫圈。按 PI-RADS V2.1 要求採1.3 圖像後處理及PI-RADS V2.1評分兩名高年資MRI診斷醫師按照 PI-RADS V2.1評分標準對例患者的圖像進行分析，並獲得一致的病灶 PI-RADS V2.1 評分。首先分析 bpMRI，T2WI主要分析前列腺及鄰近器官的形態、信號及是否發生轉移，DWI結合 ADC圖對彌散受限的病灶進行分析。間隔 5-7天後分析 mpMRI，在bpMRI基礎上再結合 DCE病灶的強化特徵分析。DCE 評估標準：陽性為與鄰近正常前列腺組織相比，出現局灶性早期強化，且在 T2WI和（或）DWI 上有相應異常發現。陰性為早期病灶無強化；或病灶彌漫性強化，但在 T2WI或 DWI上無對應的局灶性表現；或在 T2WI上表現為前列腺增生結節特徵的移行區局灶性強化。前列腺外周帶病灶的總體評分主要由 DWI 序列的評分決定，集如下序列：T1WI、T2WI、DWI及 DCE，各序列保持一致的定位、掃描角度和層厚。增強掃描使用對比劑 Gadovist 行 DCE 掃描，對比劑劑量0.1mmoL/kg，經肘靜脈團注，流速為 2ml/s。掃描序列及參數如表 1。DCE陽性結果僅對 DWI序列評分為 3分病灶的最終評分結果有影響，若 DCE結果為陽性，則最終的整體評分提升為 4分。移行帶病變的總體評分主要由 T2WI序列決定。不同於 PI-RADS V2，PI-RADS V2.1 DWI序列對 T2WI 序列評分為 2分和 3分者均有影響，若 T2WI序列評分為 3 分，而 DWI序列評分 ≤4分，則總體體評分仍為 3分；若 DWI序列評分為 5分，則總體評分為 4分；若T2WI序列評分為 2 分，而 DWI序列評分 ≥4分，則總體評分為 3分。以 PI-RADS V2.1評分 1-3為陰性， PI-RADS V2.1評分 4-5為陽性。1.4 統計學方法 應用 SPSS 26對數據進行處理，以穿刺病理結果為金標準，分別計算 bpMRI及 mpMRI的敏感度、特異度、準確度、陽性預測值、陰性預測值。表 1 前列腺 MRI 掃描序列及參數GE1.5T PHILIPS 3.0TT2-weighted imaging Axial, coronal, sagittal T2 TSE, 3 mm slice thicknessAxial, coronal, sagittal T2 TSE, 3 mm slice thicknessTR 3629ms, TE 102 ms, FA 160 ° , FOV 240 mm × 240 mm, base resolution 320mm × 224mm, NSA 1TR 3000ms, TE 110 ms, FA 90° , FOV 180 mm × 180 mm, base resolution 452mm × 255 mm, NSA 1Diffusion weighted imaging Axial, EPI, 3 mm slice thickness Axial, EPI, 3 mm slice thicknessb-values 50, 800, and 1500 b-values 0, 800, and 1500 TR 7121ms, TE minimum, NSA: 4, 10, 20 TR 3448ms, TE 71ms, NSA: 1, 3, 8Dynamic contrast enhanced imagingAxial, LAVA Flex Axial, e-THRIVE HR SENSE3 mm slice thickness 3 mm slice thicknessPerfusion temporal resolution: 20 s (total time length: 186sec)Perfusion temporal resolution: 8 s (total time length:180sec)TR 7.3 ms , TE 1min ful, TE 4.2 ms, FA 15° TR 3.3 ms , TE 1.73 ms, FA 10°
基� PI-RADSV2.1對��參數�多參數 MRI��列�����價值澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal38學者通過大量病例研究發現，PI-RADS V2評分為3的病變與有臨床意義的 PCa無顯著相關性，只需隨訪檢測即可 [20]。我們的研究有一定的局限性。首先，這是一項回顧性單中心研究，仍需要前瞻性研究來證明 bpMRI 是否等同於 mpMRI診斷有臨床意義的PCa。其次，本研究以超聲引導前列腺穿刺或根治性前列腺切除術的病理結果為金標準，僅部分為融合定位穿刺，一方面 MRI圖像顯示的病灶部位與病理標本難以準確對照，另一方面活檢的假陰性率相對較高，可能降低 mpMRI和 bpMRI的診斷效能。最後，除了提供定性參數，MRI還可以提供大量的定量和半定量參數，如 bpMRI的 ADC值，mpMRI的 DCE強化曲線等，是否與實驗室檢查如PSA、PSA-D存在相關性，在更進一步臨床應用（例如 PCa分期）中的價值均有待研究。這也是我們的下一步方向。4. �論綜上所述，基於 PI-RADSV 2.1 評分標準，bpMRI與 mpMRI兩種方案的敏感度、特異度、準確度、AUC具有一致性，診斷效能相當。DCE有助於進一步識別 bpMRI 3分病灶中的 PCa，可能有助於實現部份 PCa更早期診斷，尤其在 DWI圖像質量欠佳的時候；但同時增加了假陽性率。bpMRI優點是簡化檢查、降低成本和消除潛在的 GBCA 相關問題。選擇 bpMRI作為 PSA升高的男性進一步篩查臨床顯著癌的檢查手段是可行的。圖2a-2d：病例1，前列腺癌。圖2a前列腺左側外周帶見局灶性低信號，T2WI評分4，由於腸道產生僞影。圖2b的DWI及圖2c的ADC圖像不理想，病灶顯示欠清，DWI評分3分。圖2d病灶呈明顯早期局灶性強化，DCE陽性。bpMRI總評分3分，m p M R I總評分4分。病理結果證實為前列腺癌Gleason評分7分。圖 2a 圖 2b 圖 2c 圖 2d圖 3a 圖 3b 圖 3c 圖 3d圖3a-3d：病例2，前列腺增生伴慢性炎症。圖3a前列腺左側外周帶見局灶性低信號，T2WI評分4。圖3b的DWI圖顯示為高信號。圖3c的ADC圖為稍低信號，非綫狀或楔形，DWI評分3分。圖3d病灶呈早期局灶性強化，DCE陽性。bpMRI總評分3分，mpMRI總評分4分。病理結果為前列腺增生伴慢性炎症。
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基� PI-RADSV2.1對��參數�多參數 MRI��列�����價值澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal40p ros t a t e cance r accumula t ing mode l : combined P I -RADS v2 w i th p ros t a t e specific antigen and its derivative data. Cancer Imaging 2019; 19:26. doi: 10.1186/s40644-019-0208-6.[18] Vo s E K , L i t j e n s G J , K o b u s T , e t a l . A s s e s s m e n t o f p r o s t a t e c a n c e r aggressiveness using dynamic contrast-enhanced magnetic resonance imaging at 3T. Eur Urol 2013; 64:448–455. doi: 10.1016/j.eururo.2013.05.045.[19] Roh AT, Fan RE, Sonn GA, et al . How often is the dynamic contrast enhanced score needed in PI-RADS version 2. Curr Probl Diagn Radiol 2020; 49:173–176. doi: 10.1067/j.cpradiol.2019.05.008.[20] Liddell H, Jyoti R, Haxhimolla HZ. mp-MRI Prostate character ised PIRADS 3 lesions are associated with a low risk of clinically significant prostate cancer-A retrospective review of 92 biopsied PIRADS 3 lesions. Curr Urol, 2015, 8(2)：96-100. doi: 10.1159/000365697
Wai Tan YUNG Tammy et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 41Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu HospitalWai Tan YUNG Tammy1*, See Kit LO Raymond2, Cheng Man CHAN1, Qing Xin XU3, Yan SUN1, Sai Hang LEONG1, Si Wai LAM1, Sio Leng WONG1 AbstractObjectives: Quality of life (QOL) is the main outcome in caring for cancer patients, but little is known about it amongst the cancer patients of Macao. The McGill Quality of Life questionnaire is one of the tools for palliative care patients.Methods: This study investigated the QOL of the cancer patients in Centro Hong Neng Hospice and Palliative Care Center, Kiang Wu Hospital from 25/10/2019 ~6/10/2021 by using the McGill Quality of Life questionnaire for Chinese which has been validated and translated in Hong Kong and Taiwan. Patients admitted to the Hospice and Palliative Care Center of Kiang Wu Hospital in Macao were recruited for the study. QOL was assessed on admission, first and second week of admission. Results: The mean total QOL score was 5.04 of 10 (sd 1.0). The QOL domains with the poorest scores was physical 5.62 of 10 (sd 1.3). The support domain had the best scores of 7.58 (sd 1.9). Conclusion: Symptom control measurement and QOL evaluation using MQOL is feasible and applicable in local Macao hospice ward setting. Effects of successful intervention and areas requiring improvement are identified for further study.Keywords: Quality of life; Palliative care; Macao1Centro Hong Neng Hospice and palliative care Center, Kiang Wu Hospital2Department of Medicine And Therapeutics, Chinese University of Hong Kong3Kiang Wu Nursing College of Macao*Correspondence to: Wai Tan YUNG Tammy, tammyyung@hotmail.com1. IntroductionCancer is one of the major causes of death around the world. Palliative care is defined as “an approach aiming at improving the quality of life of patients and their families facing the problems associated with life-limiting illness”. Good general care is the key to maintaining optimal QOL. As a result, QOL serves as the final common pathway for palliative care services and should be considered as the main outcome measure. By measuring patient’s QOL, aspects requiring involvement and counseling can be recognized so that the benefit of care and treatment can be assessed. Pall iative care service was established in Macao in year 2000 as a hospital-based setting providing care for patients with advanced cancer. According to Macao Health Bureau 2018 Cancer registry, morbidity and mortality of cancer patients have been rising which has led to an increased demand for cancer-related services. Nonetheless, information regarding the efficacy of palliative care
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal42service in Macao is lacking. The current survey is the first investigation on the QOL of cancer patients admitted to palliative care service in Macao. The purpose of this study is to assess the QOL in patients with advanced cancer receiving palliative care in Macao Kiang Wu Hospital, by assessing patient QOL score on admission, first and second week of admission. The study aims to assess the efficacy of palliative care service in Macao Kiang Wu Hospital and exploring insufficiency as a basis for future improvement.Various instruments have been designed to measure QOL. McGill QOL questionnaire (MQOL) was one of the tools developed to measure that in cancer patients. It was translated into multiple languages and shown satisfactory results both in validity and reliability. , As one of the most appropriate measures for evaluation of QOL among terminal cancer patients, MQOL score serves as a useful tool for clinical researchers to assess and compare QOL in different countries. The cross-cultural validity of MQOL was investigated using a translated and modified version of Chinese MQOL-HK questionnaire which was shown to be valid and reliable. , 2. MethodPatients admitted to the Hospice and Palliative Care Center of Kiang Wu Hospital in Macao was recruited for the study. QOL was assessed on admission, first and second week of admission. Eligible patients for this QOL study must fulfill the following criteria:•Adult (age>=18years old)•Language: able to communicate effectively either in written or spoken Chinese or Cantonese• G e n e r a l c o n d i t i o n : m e n t a l l y a l e r t a n d physically well enough to complete oral or written survey, following assessment by attending physician•Ethnicity: ChineseExclusion criteria for this QOL study include:• L a n g u a g e : u n a b l e t o c o m m u n i c a t e t o investigator either verbally or in writing•General condition: unable to complete the questionnaire due to physical or cognitive limitationA total of 51 patients were eligible in this study and they were all interviewed by the investigators. During the interview, patients were informed about the purpose of this study and their consent to participate in the study obtained. Any queries on the questionnaire items were explained clearly. All the scores in the questionnaire were self-rated by patients.The McGill QOL questionnaire (MQOL) was first designed in 1995 specifically to measure the QOL of people with life-threatening illness at all stages and was revised in 1997 for cancer patients receiving palliative care. It consisted of 18 items measuring 4 main domains which include physical, psychological, existential well-being, and support. Each item was rated by patients on a numerical scale from 0 to 10, with verbal anchors at the ends of the scale. Some items are negatively phrased to avoid implicit response bias. The MQOL had been used in multicultural palliative care settings and was translated into Cantonese-Chinese by Hong Kong scholars with a measure added for sexuality. The cross-cultural validity among Cantonese-Chinese populations had been investigated by Lo et al. in year 2001 for terminal cancers patients in Hong Kong. It has demonstrated good acceptability, construct validity, convergent and divergent validity, test-retest and inter-rater reliability results on use among Hong Kong Chinese population. Cronbachs alpha for the MQOL-HK subscales ranged from 0.68 to 0.85. The test-retest reliability for the entire scale within 48 hours was 0.75. The MQOL-HK questionnaire consists of 4 main domains: physical well-being (five items), psychological well-being (six-items), existential well-being (four items), support (two items), and sexuality (one item). In our study, patient QOL were assessed in 3 different period including day of admission, 1 week after admission and 2 week after admission.
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 433. Stat ist ical analysisData we re ana lyzed u s ing t he w indows Statistical Package for the Social Science program (SPSS) version 22. Descriptive statistics consist of frequency; mean and standard deviation (SD) were used to summarize the variables studied. Differences in the total and subscale MQOL-HK scores between demographic and clinical variables were determined by the student t-test and one way analysis of variance. The statistical significance level will be set at p<0.05 throughout the analysis (two-tailed).To avoid implicit response bias, investigators were trained prior to the study. Questionnaires were filled out by patients themselves. If needed, quest ions could be read aloud by the t rained investigators to the patients.4. ResultsA total of 51 patients completed the study. The mean age of the 51 patients was 63.84 years (range 33-96). Of these 51 patients, 30 were male (58.8%) and 21 (41.2%) were female; 35 (68.6%) were married and 6 (11.8%) were divorced; 27 (52 .9%) f in ished secondary school , 3(5 .9%) finished university and 4(7.8%) had no formal education; 34 (66.7%) had no religious worship, 7(13.7%) believed in Buddhism, 6(11.8%) worship ancestors, 3 (5.9%) were Christians and 1(2%) was Catholic. The commonest diagnosis were lung cancer (n=11, 21.6%), followed by colon cancer (n=9, 17.6%), hepatocellular carcinoma (n=4; 7.8%) and gastric cancer (n=4; 7.8%). (See Table 1)Pain (64.71%), loss of appetite (33.33%), edema and fatigue (23.53%) were the commonest reported physical symptoms. (See Table 2)The mean total QOL score was 5.04 of 10 (sd 1.0). As for the scoring scales for individual domains, high scores obtained in the physical and psychological domains are actually negative, and high scores for the existential and support domains are interpreted as positive. The QOL domains with the poorest scores was physical 5.62 of 10 (sd 1.3). The support domain had the best scores of 7.58 (sd 1.9). There was an improving trend in the physical domain of pain, psychological domain and sexuality domain (from 8.3 to 8.5). However, there was a deteriorating trend over all for the other domains but without statistical significance. The mean total QOL score was on a downtrend (from 5.2 to 4.9), physical domain (from 5.9 to 5.3), existential domain (from 6.5 to 6.4), support domain (from 7.6 to 7.5). Statistically significant improvements for the worst physical symptom (p=0.03) and physical well-being (P=0.04) were achieved. (See Tables 3 to 5)
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal44Table 2. Physical symptomsPhysical symptoms symptoms1 symptoms2 symptoms3 total PercentagePain 19 11 3 33 64.71Anorexia 2 6 9 17 33.33Edema 2 6 4 12 23.53Fatigue 3 2 7 12 23.53Constipation 0 6 4 10 19.61Bloating 7 2 1 10 19.61Dyspnea 6 2 2 10 19.61Table 1. Characteristic of study subjectsMean（SD） RangeAge（years） 63.84(12.27) 33-96Sex f %Male 30 58.8Female 21 41.2ReligionWorship ancestors 6 11.8Buddhist 7 13.7Christian 3 5.9catholic 1 2No religious belief 34 66.7Marital statusSingle 8 15.7Married 35 68.6Divorced 6 11.8Widowed 1 2Education levelIlliterate 4 7.8elementary 15 29.4High school 27 52.9college 3 5.9Cancer diagnosisLung 11 21.6colorectal 9 17.6liver 4 7.8
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 45Table 3. Comparison of the mean total, domain, individual item QOL scores of 51 patientsMQOL-HK Items e 1 Mean (SD) 2 Mean (SD) 3 Mean (SD) F P valuePhysical domain 5.9 (1.3) 5.6 (1.3) 5.3 (1.3) F=2.3 0.1Physical symptom 1 6.7 (2.0) 6.7 (2.0) 5.8 (1.9) F=3.5 0.03Physical symptom 2 6.2 (2.2) 6.2 (1.8) 5.9 (1.8) F=0.3 0.7Physical symptom 3 6.4 (2.0) 5.8 (1.4) 5.9 (1.8) F=1.4 0.2Physical well-being 5.0 (1.8) 5.8 (1.3) 5.6 (1.4) F=3.4 0.04Eating 6.6 (2.6) 6.0 (2.6) 5.8 (2.6) F=1.1 0.3Psychological domain 3.0 (2.3) 2.5 (2.1) 2.6 (2.1) F=0.9 0.4Depressed 3.0 (2.9) 2.4 (2.5) 2.6 (2.5) F=0.7 0.5Anxious 3.2 (3.1) 2.5 (2.8) 2.8 (2.8) F=0.8 0.5Sad 2.7 (3.1) 2.6 (2.9) 2.3 (2.6) F=0.2 0.8Fear of future 2.6 (3.3) 2.2 (3.1) 2.2 (2.8) F=0.3 0.8Everyday seems a gift 4.3 (3.5) 3.5 (3.2) 4.2 (3.0) F=0.8 0.4Face 2.4 (3.2) 1.6 (2.8) 1.7 (2.5) F=1.2 0.3Existential domain 6.5 (1.8) 6.6 (1.8) 6.4 (1.6) F=0.2 0.8Personal existence 6.5 (2.3) 6.2 (2.4) 6.4 (2.0) F=0.2 0.8Achieving life goals 6.6 (2.6) 6.8 (2.2) 6.5 (1.9) F=0.3 0.7Life worthwhile 6.7 (2.1) 6.9 (2.0) 6.5 (1.7) F=0.5 0.6Feel good about myself 6.2 (2.4) 6.6 (2.3) 6.3 (2.0) F=0.3 0.7Support domain 7.6 (2.0) 7.7 (1.8) 7.5 (2.0) F=0.1 0.9Closeness to people 8.3 (1.7) 8.5 (1.8) 8.1 (2.0) F=0.4 0.7World is caring 6.8 (2.7) 6.9 (2.4) 7.0 (2.5) F=0.1 0.9Sexuality domain 8.3 (3.3) 8.0 (3.4) 8.5 (3.0) F=1.1 0.9Single item score 5.8 (2.0) 6.4 (1.7) 5.9 (1.7) F=1.5 0.2Mean total QOL score 5.2 (1.0) 5.0 (1.0) 4.9 (0.9) F=1.2 0.3
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal465. DiscussionI t i s rewarding tha t the effec t iveness of symptom control in palliative care ward can be demonstrated. One study has confirmed that the most frequently unmet need in terminal cancer patients was physical symptom control. Physical symptoms on admission could be better managed after admission but could relapse or worsen as the disease progressed and might be more difficult to control. Besides, worsening or relapsed symptoms could not be easily recognized early since the end stage often progresses rapidly and unexpectedly, giving insufficient time for adequate intervention.Physical well-being refers to more than just symptom control, but also to disability, handicap, and independence. Disability and handicap may deteriorate as patient approaches death and has more limited independence. But disability and handicap are not always inevitable. Individualized rehabilitation may improve not just physical but also other domains of QOL at the end of life. Above all, rehabilitation in palliative care focuses not just on any restorative potential, but also to palliate symptom of disability with support from aids and equipment.T h e e x i s t e n t i a l d o m a i n a l s o s h o w e d a deter iorat ing t rend. Terminal cancer pat ients experience a variety of existential issues, such as meaning and purpose of life, autonomy, burden on fami ly, s e l f - e s t eem, hope , r e l a t ions e t c . Terminal patients often have difficulties in facing with spiritual and existential issues. Spirituality is being recognized as an individual domain in determining the overal l QOL. As a resul t , comprehensive assessment of all the different facets and individualized interdisciplinary care by the team are important. Time, rapport, understanding, trust, better control of symptoms will also help. Current ly, chaplains , volunteers and cl inical psychologists could offer service to these patients who are willing to receive help and support in the existential domain. More structured programs and individualized psychospiritual support is needed.T h e p s y c h o l o g i c a l d o m a i n s s h o w e d a n improving trend (from 3.0 to 2.6) during the study, as a lower score in psychological domain actually mean better mental well-being. The psychological domain explores issues such as feeling depressed, worried, sad, or afraid of future. In our study, patients were not as afraid of facing death as we Table 5. The pain chartweek1 week2 week3pain 33 30 27percentage 64.71 58.82 52.94score 6.76 6 5.92Table 4. Comparison of the domain, mean total and individual item QOL scores of 51 patients, using repeated measures ANOVAMQOL-HK Domains Mean (SD) Within one week Mean (SD) Within two weeks Mean (SD)Within three weeksLinear TrendP ValuePhysical domain 5.9 (1.3) 5.6 (1.3) 5.3 (1.3) F=2.3 0.1Psychological domain 3.0 (2.3) 2.5 (2.1) 2.6 (2.1) F=0.9 0.4Existential domain 6.5 (1.8) 6.6 (1.8) 6.4 (1.6) F=0.2 0.8Support domain 7.6 (2.0) 7.7 (1.8) 7.5 (2.0) F=0.1 0.9Sexuality domain 8.3 (3.3) 8.0 (3.4) 8.5 (3.0) F=1.1 0.9Mean total QOL score 5.2 (1.0) 5.0 (1.0) 4.9 (0.9) F=1.2 0.3
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 47thought they might be. “Let nature take its course” is one of the most acceptable attitudes for the Chinese people with regard to the timing of death. For the support domain, the score was rather high. This may reflect the respect to patients offered by the health care staff and also the other caregivers. The other pert inent feature in the traditional Chinese culture is the collectivity, interdependence and extended family system and support. Dying patients need to be treated with dignity and respect which are important in our cultures.Pa in was s t i l l by far the most prevalent symptom among the worst physical symptoms (64.71%). The other prevalent symptoms were anorexia (33.33%) and fatigue (23.53%). However, from table 5, we can see that there was a downward trend on pain score from 6.76 to 5.92 suggesting better control of pain symptom. Prompt recognition and treatment of the relapsed or deteriorating symptoms is crucial . Freedom from pain was considered by patients as the most important factor in end-of-life care. Adequate symptom relief is a prerequisite for a good QOL for the patients and their families.6. ConclusionsSince physical domains and QOL have the poorest score, there is need to explore other factors like physical function, dependence and mobility. Mean QOL domain decrease with time, reflecting a need for team approach, comprehensive care, structured protocol, care plan and regular audit and CQI to improve. The study sample was relatively small . More research should be continued on QOL evaluation with the aims to better assessing t h e e f f i c a c y o f p a l l i a t i v e c a r e s e r v i c e f o r terminal cancer patients in Macao and exploring insufficiency in current service as a basis for future improvement. So as to improve the services.7. References[1] World Health Organization. Cancer pain relief and palliative care :report of a WHO expert committee. Geneva, Switzerland: World Health Organization, 1990.[2] Schipper H. Quality of life: the final common pathway. J Palliative care 1992;8(3):5-7.[3] Richards MA, Ramirez AJ. Quality of life: the main outcome measure of palliative care. Palliative Med 1997;11:89-92.[4] F i n l a y I , D u n l o p R . Q u a l i t y o f l i f e assessment in palliative care. Ann Oncol 1994;5(1):13-18.[5] Tsujikawa M., Yokoyama K., Urakawa K., Onishi K.: Reliability and validity of Japanese version of the McGill Quality of Life Questionnaire assessed by application in palliative care wards. Palliat Med 2009; 23: pp. 659-664.[6] Lo R.S.K., Woo J., Zhoc K.C.H., et. al.: Cross-cultural validation of the McGill Quality of Life Questionnaire in Hong Kong Chinese. Palliat Med 2001; 15: pp. 387-397.[7] Tsuj ikawa M., Yokoyama K. , Urakawa K., Onishi K.: Reliability and validity of Japanese version of the McGill Quality of Life Questionnaire assessed by application in palliative care wards. Palliat Med 2009; 23: pp. 659-664.[8] Cohen S.R., Mount B.M., Strobel M.G., B u i F. : T h e M c G i l l Q u a l i t y o f L i f e Questionnaire: a measure of quality of life appropriate for people with advanced disease. A preliminary study of validity and acceptability. Palliat Med 1995; 9: pp. 207-219. [9] Cohen S.R., Mount B.M., Bruera E., et. al.: Validity of the McGill Quality of Life Questionnaire in the palliative care setting: a multi-centre Canadian study demonstrating the importance of the existential domain. Palliat Med 1997; 11: pp. 3-23.[10] Schipper H. Qual i ty of l i fe : the f ina l c o m m o n p a t h w a y. J P a l l i a t i v e c a r e 1992;8(3):5-7.[11] Morasso G, Capelli M, Viterbori P,et al. Psychological and symptom distress in terminal cancer patients with met and unmet
Assessment in quality of life of patients receiving palliative care service in Macao Kiang Wu hospital.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal48needs. J Pain Symptom Manage 1999; 17(6): 402-409.[12] Moadel A. Morgan C, Fatone A, et al . Seeking meaning and hope: self-reported spiritual and existential needs among an ethnically-diverse cancer patient population. Psycho-Oncology 1999;8(50): 378-385.[13] Morita T, Tsunoda J, Inoue S, Chihara S. An exploratory factor analysis of existential suffering in Japanese terminally ill cancer patients. Psycho-Oncology 2000;9(2): 164-168.[14] Kellehear A. Spirituality and palliative care: a model of needs. Palliat Med 2000;14:149-155. [15] Bolmsjo I. Existential issues in palliative care-interviews with cancer patients. J Palliative Care 2000;16:20-24.[16] Cella DF, Tulsky DS. Measuring quality of l i fe today: methodological aspects . Oncology 1990; 4:29-38.[17] Tsuei YT, Hwang MTC. Hopice theory and practice. Taipei, Taiwan: Chinese medicine Technology 1992: 202-215.[18] Steinhauser KE.,Christakis NA,Clipp EC, et al. Factors considered important at the end of life by patients, family, physicians and other care providers. JAMA 2000; 284:2476-2482.
Kwong Ho TAM et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 49澳門乳腺癌篩查的模式探討Exploring the future of breast cancer screening in Macao談光濠 1，段耀菲 2，劉百球 3，彭祥佑 2，檀韜 2*Kwong Ho TAM1, Yao Fei DUAN2, Edmundo Patricio LOPES LAO3 , Cheong Iao PANG Patrick2, Tao TAN2*摘要乳腺癌為澳門近十年嚴重威脅女性健康最常見的惡性腫瘤。大量醫學證據表明，乳腺癌篩查可以提高乳腺癌早期診斷率、降低病死率。目前，歐美國家已有較系統的乳腺癌篩查方法，中國亦開展多個乳腺癌篩查項目，都有明確數據支持其效益；若以人工智能為乳腺癌篩查的輔助工具，除了可提高診斷的精確性和效率，亦可解決人手不足等問題。澳門在乳腺癌篩查發展上有其特點，在平衡本澳流行病學、資源及人口特徵後，建議應該在原有機會性篩查的基礎上，先利用乳腺癌風險模型找出高風險人群，再進行影像學檢查，通過數據的建立及反饋，逐步建立本地的女性乳腺癌篩查模式，若能配合人工智能技術，將能增加其效益。關鍵詞：乳腺癌；篩查；人工智能；澳門Abstract Breast cancer is the most common malignant tumor in Macao that has seriously threatened women’s health in the last decade. There are abundant medical evidences that breast cancer screening can increase the early diagnosis rate of breast cancer and reduce the mortality rate. Nowadays, evidences have supported that there are positive impact on both standard breast carcinoma screening mode in Western countries and breast carcinoma screening programs in China. Artificial intelligence, as accessibility tools, can improve the accuracy, efficiency and shortage of human power in screening. In Macao, there are lots of barriers, which are local epidemiology, resource and demographic characteristic, in the development of breast carcinoma screening. On the base of the current screening mode, we suggest that the high risk women are detected by risk assessment initially then followed by imaging investigation. Finally, the suitable screening mode for Macao women is established step by step through data collection and feedback. Combination with artificial intelligence may act as a spur to greater efficiency.Key words: Breast Carcinoma; screening; Artificial Intelligence; Macao1Ocean Gardens Health Centre, Health Bureau, Macao, China2Faculty of Applied Sciences, Macao Polytechnic University, Macao, China3Department of Cardiology, Conde de São Januário General hospital, Health Bureau, Macao, China*Correspondence to: Tao TAN, taotan@mpu.edu.mo
Exploring the future of breast cancer screening in Macao第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 535. 澳門乳腺癌篩查的模式探討根據澳門癌症登記年報（2009至 2020年），女性乳腺癌的發病及死亡率一直占據女性癌症中第一及第三位，發病人數從每年 136例（2009年）至 279例（2020年）；其中以 50-69歲年齡段占比例最高，2020年為 59.5%。目前本澳的乳腺癌篩查模式為機會性篩查，婦女因各種原因主動到醫療機構進行篩查。根據各地經驗及醫學證據得出，乳腺癌是可以通過無創的影像篩查早期發現，及早治療明顯關係到其預後，提高女性乳腺癌的早診率、保乳率和生存率。在早期階段識別患有乳腺癌風險的女性，會有更多的機會提供及時的治療和幹預措施，不僅可以減少患者的痛苦和不良後果，還可以顯著改善治療成功的可能性。充分的證據證明乳腺癌篩查的益處大於其可能的弊端。然而，我們也應該註意到，乳腺癌篩查並非沒有缺點。一些潛在的弊端包括可能的假陽性結果、過度診斷以及心理和經濟負擔。然而，通過謹慎的篩查方法選擇和評估以及有效的隨訪管理，可以最大程度地減少這些弊端的影響，以確保篩查的整體效益更大於其可能的不良影響。總結，乳腺癌在澳門是影響民生的重大課題，群體篩查的早期乳腺癌檢出比例高於機會篩查 [17]，結合澳門的經濟發展條件，群體篩查是目前最有效的方案。目前為止，本澳還未開展以群體為基礎的女性乳腺癌篩查；借鑒英美國家的經驗，若以政府作為主導或利用保險業提供服務，雖然引入 AI技術可即時解決篩查上人力資源問題，還需要考慮其它配套，如篩查後的跟進及整體醫療環境等，顯然短期內是不可行的，但可先進行有關的研究，為中長期的推行積累數據和運行條件。無論如何，癌症篩查的政策必須與當地實際情況相平衡才會對社會有最大的效益；而澳門亦有一些成功的癌症早期篩查計劃可供參考，如子宮頸癌及大腸癌篩查計劃。對起步階段的本地女性乳腺癌群體篩查，建議可先進行先導計劃或由某一年齡層開始，然後跟據參與意願及資源逐步協調與安排。與歐美國家及國內相比，澳門在乳腺癌篩查的發展困難上既有相似點亦有本地特點。第一，缺乏本地數據，雖然偶有民間組織發起的篩查活動，但缺乏大規模高品質的研究評估，使篩查缺乏方向性；第二，人力資源問題，根據澳門醫學專科學院及澳門醫療專業委員會資料顯示，截至2023年 6月，本澳有 34名放射科院士 [18]及 80名放射師 [19]，這數字遠不及群體篩查所需人力，使群體篩查模式難以實行；第三，澳門地區是多元化人口群體，雖然大部份為華人，但融合了歐亞混血後裔、葡萄牙人及其它國籍人士，使在選擇篩查工具上變得複雜。基於以上的事實，我們總結出兩個解決方案：A.本地數據問題：可參考國內經驗，先以問卷形式對特定人群進行初步篩查，然後對高風險人群進行 BUS和 /或 MAM；結合本地流行病學情況及在大腸癌篩查計劃的經驗，建議以 50-54歲（5年）作為首批篩查對象的年齡層，再跟據實際情況再逐步擴展。另外，在乳腺癌風險預測問卷上，至今沒有一個模型能夠對所有人種的乳腺癌風險進行全面評估，現時大部份都是基於西方人群建立的，在華人社區中的應用價值可能有限。改良 Gail和 IBIS/Tyrer-Cuzick模型為目前常用的工具，有研究指在中國女性中，其預測 5年乳腺癌風險的 AUC分別為 0.665和 0.786[20]，證明均適用於中國女性。因此，我們可在經典模型的基礎上結合澳門的實際情況，逐步構建適合澳門女性的乳腺癌風險評估。B.人力資源及人口特徵問題：針對這一問題，AI是一個有效的突破口；上文已討論 AI在人力資源缺乏下的應用及各國的經驗。另外，針對澳門不同人種的乳腺組織和腫瘤類型的特徵差異，可逐漸利用 AI收集數據及研發適用於澳門地區女性的乳腺癌篩查 AI。這樣的 AI可以更快更準確地讀取乳腺影像並識別潛在的癌症，除解決人力及人口特徵問題外，為更多的潛在癌症患者帶來更高的治癒率。
�門乳������式��澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal546. 結論平衡各種因素，我們認為目前沒有充分的證據支持或反對利用影像學方法在澳門對女性乳腺癌進行群體篩查。但是，我們可以在機會性篩查的基礎上，首先以傳統乳腺癌風險評估模型對50-54歲的本地常住女性人口進行初步篩查，評估出的高風險人群後再結合每 1-2年的 BUS和 /或MAM；通過數據的建立及反饋，逐步建立本地的篩查模式。同時亦可逐步使用 AI系統，加速乳腺癌篩查的發展、減少篩查對人手的依賴，釋放人力至其他醫療領域中。7. 參考文獻[1] Sung, Hyuna, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 2021, 71.3: 209-249. doi.org/10.3322/caac.21660.[2] 沈松傑, 孫強, 黃欣, 李炎, 李玥翀, 牛梓涵, ... & 周星彤. (2022). 中國女性乳腺癌篩查指南 (2022 年版). 中國研究型醫院 . doi: 10.19450/j.cnki.jcrh.2022.02.003.[3] Huang, Yu-Len, Dar-Ren Chen, and Ya-Kuang Liu. “Breast cancer diagnosis using image retrieval for different ultrasonic systems.” 2004 International Conference on Image Processing, 2004. ICIP’04.. Vol. 5. IEEE, 2004.[4] Lehman, Constance D., et al . National pe r fo rmance benchmarks fo r mode rn screening digital mammography: update f rom the Breas t Cance r Su rve i l l ance Consortium. Radiology, 2017, 283.1: 49-58. doi.org/10.1148/radiol.2016161174.[5] Lauby-secretan, Beatrice, et al. Breast-cancer screening―viewpoint of the IARC Working Group. New England journal of medicine, 2015, 372.24: 2353-2358. doi: 10.1056/NEJMsr1504363. [6] Marmot, Michael G., et al. The benefits and harms of breast cancer screening: an independent review. Bri t ish journal of cancer, 2013, 108.11: 2205-2240. doi.org/10.1038/bjc.2013.177.[7] Women’s Health Policy, Coverage of Breast Cancer Screening and Prevention Services. Accessed at https://www.kff.org/womens-health-policy/fact-sheet/coverage-of-breast-cancer-screening-and-prevention-services/, on 23rd June 2023.[8] World health Organization. WHO position paper on mammography screening. Accessed https://www.who.int/publications/i/item/who-posi t ion-paper-on-mammography-screening, on 23rd June 2023. [9] Screening for breast cancer: Strategies and recommendat ions; Uptodate . Assessed at ht tps: / /www.uptodate .com/contents /screening-for-breast-cancer-strategies-and recommendations?search=breast%20cance r%20sc reen ing&source=sea rch_r e s u l t & s e l e c t e d Ti t l e = 1 ~ 1 2 9 & u s a g e _type=default&display_rank=1, on 24th June 2023.[10] Schünemann, Holger J., et al. Breast cancer screening and diagnosis: a synopsis of the European Breast Guidelines. Annals of internal medicine, 2020, 172.1: 46-56. doi.org/10.7326/M19-2125.[11] Cardoso, Fátima, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology, 2019, 30.8: 1194-1220. doi.org/10.1093/annonc/mdz173.[12] 陳萬青 , e t a l . 中國城市癌症早診早治專案進展. 中國腫瘤, 2019, 28.1: 23-25. doi: 10.11735/j.issn.1004-0242.2019.01.A003.[13] Lauritzen, Andreas D., et al. An artificial intelligence–based mammography screening p r o t o c o l f o r b r e a s t c a n c e r : o u t c o m e and rad io log is t work load . Radio logy, 2022 , 304 .1 : 41-49 . do i .o rg /10 .1148 /radiol.210948.[14] Aboutalib, Sarah S., et al. Deep learning t o d i s t i n g u i s h r e c a l l e d b u t b e n i g n mammography images in breast cancer screeningdeep learning in mammography.Clinical Cancer Research, 2018, 24.23: 5902-5909. doi.org/10.1158/1078-0432.CCR-18-1115.[15] Mayo, Ray Cody, et al. Reduction of false-posi t ive markings on mammograms: a retrospective comparison study using an
Exploring the future of breast cancer screening in Macao第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 55artificial intelligence-based CAD.Journal of digital imaging, 2019, 32: 618-624. doi.org/10.1007/s10278-018-0168-6.[16] HuiyiHuiying Medical Technology (Beijing) C o . , L t d . . A c c e s s e d a t h t t p s : / / w w w.huiyihuiying.com/en/gsgk.html, on 24th June 2023.[17] 沈松傑, et al.“中國女性乳腺癌群體篩查與機會性篩查的比較研究 .” 中華外科雜誌 59.2 (2021): 109-115.[18] 澳門醫學專科學院院士名單 . A s s e s s e d at https://www.am.gov.mo/, on 24th June 2023.[19] 澳門特別行政區政府醫療專業委員會 , 醫療人員資格認可名單. Assessed at https://www.cps.gov.mo/#clg19093, on 24th June 2023.[20] Z h a n g , L e , e t a l . U s e o f r e c e i v e r opera t ing charac te r i s t i c (ROC) curve ana lys i s fo r ty re r-cuz ick and Ga i l i n b r e a s t c a n c e r s c r e e n i n g i n j i a n g x i p r o v i n c e , C h i n a . M e d i c a l s c i e n c e monitor: international medical journal of experimental and clinical research, 2018, 24: 5528. doi: 10.12659/MSM.910108.
Hou Man LO et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal56A review on pityriasis rubra pilarisHou Man LO1*, Wo On CHAO2, Hong ZHANG3AbstractPityriasis rubra pilaris (PRP), also known as pityriasis pilaris, is a rare chronic inflammatory skin disease characterized by cutaneous scaling erythematous and clusters of small follicular papules which can coalesce into red-orange scaly patches and have a similar appearance of psoriasis. Hyperkeratosis of the palms and soles may also be present in PRP patients. There is a lack of information in the study regarding the precise incidence rate or prevalence of PRP, but some scientists proposed an incidence of 1 case in 3500-50,000 patients consulting with a dermatologist. The etiology and pathogenesis of PRP remains unclear, although several hypotheses claim that genetic factor, vitamin A deficiency, dysfunction in keratinization, endocrine disturbance, infections, and autoimmune disease are associated with the pathogenesis of PRP, but further research is needed. PRP can be divided into six subtypes, according to its clinical features, age of onset and prognosis. The histopathology of PRP is characterized by epidermal hyperkeratosis, follicular plugging, “checkerboard” pattern of parakeratosis, mild irregular acanthosis, and liquefaction degeneration of basal cells. Although there is no medication approved by the US Food and Drug Administration (FDA), most practitioners recommend combination therapy which consists of topical agents (such as emollients, keratolytic agents etc.), and systemic agents (such as oral retinoid) as the first-line treatment for PRP.Keywords: Pityriasis rubra pilaris; Pathogenesis; Clinical manifestation; Histopathology; Treatment1 Department of Dermatology, Peking University Third Hospital, Beijing, 100191, China2 Chao’s Medical Centre, Macao SAR 999078, China3 Department of Dermatology, First Affiliated Hospital and Institute of Mycology, Jinan University, Guangzhou 510632, China *Correspondence to: Hou-Man LO, Department of Dermatology, Peking University Third Hospital, Beijing, 100191, China. Email: lohoumandoctor@163.com.1. IntroductionPityriasis rubra pilaris (PRP) is a chronic in f l ammato ry papu losquamous sk in d i sease of unknown etiology. It was first described by Tarral in 1835, and had been fully characterized by Devergie in 1856. The spectrum of PRP was initially divided into five subtypes using a widely recognized classification scheme proposed by Griffiths in 1980, but due to the association with HIV infection which presents as a distinct entity, a sixth subtype was added into the classification of PRP in the last century. The clinical manifestations may vary among these 6 subtypes, but one mutual skin eruption is noted across all subtypes, which is various sizes of distinct, well demarcated, red-orange plaques covered with grayish-white scales. This is one of the characteristic appearances of PRP. Another characteristic feature of PRP is small islands of normal skin with the erythema, also known as “islands of sparing”. These two clinical features are fundamental to the diagnosis of PRP. Histopathological findings also play an
A review on pityriasis rubra pilaris第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 57important role in the diagnosis of PRP, especially the appearance of mild, irregular, psoriasiform acanthosis of the epidermis along with overlying “checkerboard” pattern of parakeratosis is the most common f inding under the microscopy. Although none of the medications for PRP have been approved by the US FDA, nowadays most practitioners recommend combination of topical and systemic treatment as a first line therapy for PRP. However, with the emergence of biologic agents, such as secukinumab and ustekinumab etc., the therapeutic modalities for PRP have come into a new era.2. EpidemiologyNo reliable data concerning the prevalence and incidence rate of PRP have been published. But W.A.D Griffiths reported that about 1 in 5,000 new patients consulting with a dermatologist could be due to PRP, and all races could suffer from PRP, with no distinct differences in the incidence between both genders. Meanwhile, he proposed that all ages, including children, could be affected, and there seemed to be two peaks at the onset of the disease: the first peak could be at the age of 1-10, the second could be at the age of 50-60.[1] However, an Indian study suggested the incidence of PRP was approximately 1 in 50,000 new patients.Although most of the cases are acquired, a French scientist had observed and reported the first familial occurrence case of PRP in 1910. Patients who suffered from genetic form of PRP, up to 6.5% presented a positive family history, and the onset of the disease usually began in infancy or childhood with an autosomal dominant inheritance pattern in most cases.3. Etiology and pathogenesis3.1 Genetic FactorAlthough most cases of PRP are sporadic, approximately 5% of the cases are associated with a positive family history and are classified as the genetic form. The onset of familial cases of PRP usually begins in infancy or childhood with an autosomal dominant inheritance pattern, variably wi th an incomplete penetrance, and var iable expression. Gál et al. [2] performed a genetic screening of CARD14 gene on 19 patients who have been diagnosed with different types of PRP, and revealed two mutations (rs117918077, rs114688446) and six polymorphisms (rs2066964, rs28674001, rs11653893, rs34367357, rs2289541, rs11652075). Israelis and Taiwanese scientists have also reported similar results. Some scientists found that mutation in CARD14 is associated with familial and non-familial forms of psoriasis. As a result, PRP and psoriasis share some similar clinical manifestations, and it leads to a misdiagnosis by dermatologists.3.2 Vitamin A deficiency and dysfunction in vitamin A metabolismIn the past , vitamin A deficiency and the decreased serum level of retinol-binding-protein (RBP) were believed to be associated with the pathogenesis of PRP. Abnormalities in the result of serum vitamin A levels, dark adaptation threshold tests, and serum vitamin A tolerance tests are indications to prove the relationship between vitamin A deficiency and PRP, but none of these tests give consistent results in PRP, so there is no conclusive evidence to support the view that PRP is a disease of vitamin A metabolism. However, administration of toxic doses of vitamin A and minimum dosage of systemic vitamin A were proven to be effective in treating PRP patients. Some case reports described juvenile PRP patients could be treated with minimum dosage of systemic vitamin A. Since vitamin A level of peripheral blood of the patient remained within a normal range before and after the treatment, therefore it was believed that the clinical efficacy was due to pharmacological action of vitamin A but not a supplementary effect of vitamin A. Alitretinoin, an endogenous vitamin A derivative was proven to be effective for the treatment of PRP. Yun et al. [3] administered oral alitretinoin (30 mg/day) for 7 months to a 15-year-
A review on pityriasis rubra pilaris澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal58old Korean boy, who suffered from type IV PRP, and whose skin lesions eventually improved without recurrence for 9 months. Therefore, vitamin A may be correlated with the pathogenesis of PRP, but whether vitamin A deficiency is one of the causes of PRP is still unknown, and further research is needed.Decrease in the serum level of RBP is also considered as one of the causes of PRP. A.F.Finzi et al. [4] measured the serum level of RBP in 11 patients with PRP and some of their close relatives. The level of RBP was markedly reduced in every patient , and in some of the relat ives, so they proposed that the defective synthesis of RBP is highly associated with the pathogenesis of PRP.3.3 Autoimmune and endocrine disordersIn recent years, some reports have associated the pathogenesis of PRP with hypothyroidism. Some case reports mentioned PRP patients are associated with autoimmune hypothyroidism which presented rapid and complete response after a 30 days of thyroid hormone replacement, without any other systemic treatment, so there is a strong correlation between hypothyroidism and the pathogenesis of PRP. In fact, thyroid hormone is essential to the conversion of ingested carotenes to vitamin A, that’s why patients with hypothyroidism may also present vitamin A deficiency. Even though the serum level of vitamin A is mostly normal in PRP patients, it doesn’t strictly reflect their reserves, especially in the liver. Therefore, hypothyroidism may induce an abnormality of vitamin A metabolism, causing PRP. Except hypothyroidism, other autoimmune diseases, such as dermatomyositis, vitiligo and subacute lupus etc. are also believed to have an association with PRP.3.4 Human Immunodeficiency Virus (HIV) and other infectionIn 1990s, HIV infection has been associated with the pathogenesis and development of PRP; therefore, based on the classif ication scheme proposed by Griffiths in 1980, type-VI PRP has been added to the classification. The relationship between PRP and HIV infection was firstly reported by Blauvelt et al. [5], 2 patients with PRP and HIV infection were reported, both of them suffered from severe form of PRP, and the onset of PRP preceded the positive result of HIV infection. Miralles et al. [6] were the first to propose the designation of a new category of PRP (Type-VI). They reported a 32-year-o ld Br i t i sh homosexual male who was found to be HIV positive, with subsequent skin eruptions including inflammatory follicular pustules and papules, prominent on the face, with progressive lesions on the trunk, turning into desquamative erythroderma and he died as a result of acute renal failure, Candida Septicemia and disseminated intravascular coagulation. The patient was refractory to different kinds of treatment, including etretinate, zidovudine, isotretinoin, prednisone etc. Although only a few cases of PRP patients with HIV infection have been reported, none had developed PRP before HIV infection was confirmed, so it is strongly believed that in these patients HIV infection is not coincidental. Compare with other subtypes of PRP, the clinical manifestations of these patients are significantly more severe with a more rapid evolution, so it is widely recognized that HIV infection may play an important role in the onset and development of PRP. Other infect ions , such as cytomegalovirus , influenza virus, group A β- hemolytic streptococcus, Epstein–Barr virus (EBV), or even SARS-CoV-2 are a lso suspected to be associa ted wi th the pathogenesis of PRP.4. Clinical manifestat ionsThe classification scheme of PRP proposed by Griffiths in 1980 is widely accepted. In this classification scheme, PRP is further divided into 5 distinct subtypes, and the last subtype also known as HIV-associated PRP is marked as type-VI. (Table 1) These 6 subtypes were categorized by the age of onset, lesion distribution, clinical course, and prognosis. (Table 2) Although each variant of PRP has its own characteristics, there are some cardinal
A review on pityriasis rubra pilaris第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 59features that appear across subtypes in variable degrees, including red-orange papules and plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis (Figure 1, 2, 3). Lesions of PRP are usually asymptomatic, although a small portion of cases have reported pruritis and burning sensation on the involved part of skin.4.1 Type-Ⅰ: classical adult onsetI t i s the mos t common type of PRP and represents approximately 55% of all PRP cases. The onset of type-I PRP occurs in adult stage, over 80% of this type of patients have a self-limiting course and spontaneous remission or even resolution within 3 years. Type-I PRP is mainly characterized by classic red-orange papules and plaques with “islands of sparing” (it represents the sporadic normal appearance skin within the involved area), perifollicular keratotic papules with hair in the center, and waxy palmoplantar keratoderma. The lesions usually begin on the upper half of the body, especially the scalp, manifesting erythema covered with grayish fine scale on the scalp, which may mislead the dermatologist to diagnose it as seborrheic dermatitis. Characteristic hyperkeratotic follicular papules can occur both in patches of erythema and the surrounding areas of uninvolved skin, and there is a predilection on the dorsum of the first and second phalanges, extensor surface of the wrists, elbows, and knees. Along with the progression of the disease, more papules may erupt and coalesce into red orange to salmon color scaly plaques, with a rough texture and feels like a “rough rasp” or “nutmeg grater”.Pa lms and so les a re o f t en invo lved and manifest as palmoplantar keratoderma, which is characterized by symmetrical thickening of palms and soles with orange yellow color. Patients may feel the skin is dry and tense, fissures can be seen on patients’ palms and soles. Nails are commonly involved, the manifestations varied from yellow-brown discoloration and thickening of the nail plate, subungual hyperkeratosis, but characteristics of psoriasis such as onycholysis and nail pitting are rare. In some rare cases, oral mucous membrane can be involved, with diffuse hyperkeratosis or erythema with white strike, resembling lichen planus. In some severe cases, PRP can turn into widespread erythroderma, with systemic symptoms such as high fever, hypohidrosis, depraved appetite, emaciation, and secondary infection etc.4.2 Type-Ⅱ: atypical adult onsetIt accounts for about 5% of all PRP patients. The onset of this type of PRP usually occurs in the middle-aged. The manifestations of type-II PRP are significantly different from the classical adult onset PRP, characterized by eczematous-like skin eruptions, ichthyosiform scale on lower extremities, and coarse palmoplantar keratosis. Alopecia is also a common clinical feature of type-II PRP. It usually bears a chronic clinical course, only approximately 20% of these patients show remission within 3 years, and few of them get fully recovered.4.3 Type-Ⅲ: classical juvenile onsetType-III PRP is one of the expressions of PRP among children, but it only affects 10% of all PRP patients. The onset of this form is usually at the age of 5-10 years, while Allison et al. [7] reported 8 out of 17 patients with type-III PRP have the onset in the late teens (aged 16-19 years). The clinical manifestations of type-III PRP are identical to type-I PRP, and the most common sites involved were the back (100%), chest (88%), arms (88%), and legs (83%), which is different from type-I PRP (the first and second phalanges, extensor surface of the wrists, elbows, and knees). Type-III PRP is usually self-limited, with a better prognosis and shorter clinical course than type-I PRP. Frequent spontaneous resolution within a year is always observed. 4.4 Type-Ⅳ: circumscribed juvenile onsetType-IV PRP is the most common expression of PRP among children. It affects almost a quarter of all PRP patients, and the onset of this variant usually occurs in prepuberty stage. The clinical manifestations of type-IV PRP have a significant difference to type-I/III PRP. It is characterized
A review on pityriasis rubra pilaris澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal60by a well-demarcated group of hyperkeratotic follicular papules with an erythematous base and palmoplantar keratoderma, and the skin eruptions are mostly confined to the elbows, knees, palms, and soles. The course is usually chronic, with a 3-year remission rate of not more than 40%. Since some reports described over 50% of this type of patients can recover within 6 months, the prognosis of type-IV PRP is uncertain.4.5 Type-Ⅴ: atypical juvenile onsetThis variant subtype of PRP is rare, affecting up to 5% of patients. It usually presents at birth or develop in infancy and early childhood. The majority of patients with hereditary PRP belong to this subtype, and most of them present with mutations in the CARD14 gene. It has similar c l in ica l mani fes ta t ions o f type- I I I PRP, bu t is characterized by scleroderma-l ike changes involving the palms and soles. It often has a chronic course, and the lesions show an obvious resistance to treatments.4.6 Type-Ⅵ: HIV-associatedType-VI PRP occurs in pat ients infected w i t h H I V, u s u a l l y w i t h o u t e v i d e n c e o f immunosuppression. The manifestations of type-VI PRP are similar to type-I PRP, with symmetrical, most ly asymptomat ic erupt ions composed of h y p e r k e r a t o t i c f o l l i c u l a r p a p u l e s b a s e d o n erythematous and may coalesce into scaly plaques. This type of PRP is also characterized by prominent follicular plugging with formation of spicules. Other diseases which present similar follicular occlusion of type-VI PRP, such as acne conglobata, hidradenitis suppurativa, and lichen spinulosus may occur concurrently in the same patient with type-VI PRP. Erythroderma is a common complication of type-VI PRP. This type of patients may have more severe symptoms and are resistant to non-biological therapy.5. Histopathologic and dermoscopic f indingAs PRP is a type of papulosquamous diseases, it is easily confused with other papulosquamous diseases, especially psoriasis, so histopathological examination plays an important role in the diagnosis of PRP. Hematoxylin and eosin (H&E) staining biopsy is considered to be the gold standard of PRP diagnosis. Under the microscope, characteristic PRP plaques present irregular, psoriasiform acanthosis o f t h e e p i d e r m i s a c c o m p a n i e d w i t h a v e r y characteristic overlying “checkerboard” pattern of parakeratosis, which appears in both vertical and horizontal directions. Another important clue for the diagnosis of PRP is prominent follicular keratosis with shoulder parakeratosis. Epidermal spongiosis and focal acantholytic dyskeratosis can also be discovered in PRP patients. (Table 3) Histopathological examination is an important method to differentiate PRP from psoriasis. Findings such as thick, rather than thin, suprapapillary plates and lack of neutrophils in the stratum corneum are helpful in distinguishing PRP from psoriasis.S o m e d e r m a t o l o g i s t s p r o p o s e d t h a t dermoscopy is a reliable diagnostic tool to make a differentiation between PRP and plaque psoriasis (PP). They discovered some specific distinguishing dermoscopic patterns that may assist in the clinical d iagnos is of PRP and PP. Both s tudies have concluded similar differences between PRP and PP under dermoscopy. PRP is characterized by keratotic follicular plugs and a central hair lying in a round or oval yellowish area with or without linear vessels, while PP is characterized by clusters of dotted-like capillaries and grayish-white flaky scales lying in a bright red area.6. TreatmentsDue to the uncertain etiology and pathogenesis o f P R P, e x p l o r i n g e f f e c t i v e a n d e f f i c i e n t medications for the treatment of PRP is one the biggest challenges for dermatologists. Until now, there are no specifically effective treatments covers all types of PRP that are approved by the US Food and Drug Administration (FDA). Empirical treatments are implemented in most of the cases.
A review on pityriasis rubra pilaris第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 616.1 Topical TreatmentTopical treatments are essential and highly r e c o m m e n d e d t o t h e m a n a g e m e n t o f P R P. According to a case series of 50 patients diagnosed with PRP by histopathologic and clinical evidence, Ross et al. [13] found that emollients (90%, 45/50) were the most reported topical therapy, followed by corticosteroids (76%, 38/50), and urea (68%, 34/50). Among these topical medications, emollients were the most effective with 76% users reporting helpfulness, meanwhile type-III PRP patients believed to have a good response to emollients combined with topical corticosteroid.Using topical corticosteroid independently in PRP pat ients didn’t show a good curat ive effect, while type-IV PRP patients showed a good clinical response to topical corticosteroids. In some circumstances, topical corticosteroids were not suitable for patients, and topical calcineurin inhibitor such as pimecrolimus cream 1% was an effective alternative to corticosteroid. Calcipotriol is a vitamin D derivative, which was reported to have a great response in type-II to type-IV PRP patients, but in mixed type III/IV PRP patients, they only showed a slight remission after using Calcipotriol ointment.Topical retinoids, such as 0.025% tretinoin and 0.1% tazarotene gel were reported with a great effectiveness in PRP patients, especially 0.1% tazarotene had shown a significant improvement in type IV PRP patients.In summary, although some topical medications have a great effectiveness in treating PRP, curative effect is not prominent and consistent if topical therapies are acting as a monotherapy in treating severe PRP patients. Hence, experts have reached the consensus that topical therapy in combination with systemic therapy is considered as first-line therapy for PRP.6.2 Systemic TreatmentSys temic the rap ie s a re ind ica t ed in the treatment for severe type of PRP, and are usually implemented with topical therapies. Currently, there isn’t any formal guideline for the treatment of PRP or any randomized controlled trials to reflect the accurate efficacy of the PRP systemic treatments. Ross et al. [13] depicted that retinoid (64%, 32/50) was the most popular medication in the systemic therapies for PRP, followed by methotrexate (42%, 21/50) and light therapy (26%, 13/50). Kromer et al. depicted a similar result with Ross, besides that, among a variety of systemic retinoids, isotretinoin (61.1%, 102/167) showed the highest excellent response rate, followed by etretinate (47%, 54/115) and acitretin (24.7%, 43/174). In contrast, Kettering et al. [14] reported that methotrexate (76%, 13/17) had the highest success rate in treating patients with PRP, while retinoids (acitretin and isotretinoin) h a d o n l y ( 3 5 % , 6 / 1 7 ) i n t h e s u c c e s s r a t e . Moreover, according to several case reports, some immunosuppressive agents such as azathioprine and cyclosporine showed great clinical response in PRP patients. So, whether methotrexate or retinoid should be considered as first-line systemic therapy is still controversial.Although vitamin A deficiency hasn’t been proven to be associated with the pathogenesis of PRP, in fact, the serum vitamin A level of PRP patients is generally normal. Despite the uncertain relationship between vitamin A deficiency and PRP, several case reports depicted that both high-dose and low-dose of systemic vitamin A were effective treatment of PRP, even though the pharmacologic principle of this therapy is still unknown.Even though monotherapy and combination t h e r a p y o f s y s t e m i c m e d i c a t i o n s , s u c h a s ora l ac i t re t in monotherapy, ora l i so t re t inoin m o n o t h e r a p y, m e t h o t r e x a t e m o n o t h e r a p y, combination therapy of methotrexate with retinoids have been proven to be effective for PRP, adverse effects have become a tremendous obstacle for the systemic treatment of PRP, especially in oral retinoids. Kettering et al. [14] conducted a study lasting for over 600 days of Kaplan-Meier survival analysis in systemic treatments for PRP, showing retinoids with the lowest median survival rate of only 32%, while biologics had 40% median
A review on pityriasis rubra pilaris澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal62survival rate, and methotrexate took the first place being up to 78% in median survival rate. The study also showed that retinoids (54%) had the highest proportion in causing adverse effects which led to failure, compared with biologics and methotrexate with only 12% and 25% respectively. Kromer et al. [15] reported that compared with methotrexate and biologic agents, retinoid had higher rates of adverse events as systemic therapies for PRP. Different kinds of adverse effects have been reported, including musculoskeletal pain, dyslipidemia, e levated l iver enzymes, paronychia , fa t igue, elevated creatinine, dryness of skin and/or mucosa, and retinoid dermatitis.6.3 Biologic AgentsRecently, with the emergence of biologic agents, their utilization rate in treating a variety of dermatoses has marked a s ignif icant r ise , especially in the treatment of psoriasis, PRP, atopic dermatitis. Biologic agents were renowned for their high efficacy, good specificity, and favorable risk profile. In addition, scientists found that there was a significant increase in the expression level of innate cytokines, such as IL-23, TNF-α, IL-12, IL-22, IL-17A etc. in PRP patients’skin lesions, so treatments targeting IL-23 and TNF pathway have been proven to be effective for refractory PRP patients. Several monoclonal antibodies have been reported to show an excellence response in treating PRP patients, such as TNF inhibitors, IL-12/23 inhibitors, and IL-23p19 blocker.6.3.1 TNF-α inhibitorsAmong TNF-α inhibi tors , inf l iximab has been used to treat PRP patients most frequently, with 5 mg/kg being the most favorable dose for PRP patients, and the duration of treatment may continue to several weeks. According to a review of the utilization of biologicals in treating PRP, 60% of cases applied infliximab as a therapy for PRP combined with other treatments, such as topical or systemic corticosteroids, methotrexate, and oral acitretin. Infliximab has shown a good efficacy for the treatment of PRP, according to this review, as approximately two-third (68%, 25/37) of cases reached a marked clinical response (MR, >75% clearance of PRP lesions) or complete clinical response (CR, >95% clearance of PRP lesions). By contrast, only 32% cases showed partial clinical response (PR, 50-75% clearance of PRP lesions) or no clinical response has been observed. [16] Other TNF-α inhibitors, such etanercept and adalimumab have also been reported to have a good response in the treatment of PRP, by having 53.3% and 46.4% in the rate of MR to CR, retrospectively. However, among all the biologics in treating PRP, infliximab had the highest rate of adverse events, such as allergic reactions and infections, so the value of TNF-α inhibitors in treating PRP needs a further consideration.6.3.2 IL-(12)/23 inhibitors and IL-17A inhibitorsUstekinumab was the most used IL-12/IL-23 inhibitors in treating PRP. It is reported that nearly 80% PRP patients can achieve MR to CR after treating with ustekinumab, and only a minority of patients showed PR or no response to ustekinumab. Surprisingly, only a few of the cases have reported side effects by using ustekinumab in treating PRP. Ustekinumab and Acitrein have also be reported as a successful treatment of a type-III PRP child. So, ustekinumab is a kind of valuable biologicals in treating PRP with a considerable safety profile. Secukinumab is a monoclonal antibody which inhibits IL-17A. It has been reported as a valid biologic agent for the treatment of PRP. Boudreaux et al. [17] conducted a study by using PASI 75, PASI 90, PGA, and DLQI scores to evaluate the clinical efficacy of secukinumab in treating PRP, and they found after a 24-week course of secukinumab, PRP patients achieved PASI 75 and PASI 90 by 55% (6/11) and 27% (3/11), retrospectively. Patients’ PGA and DLQI scores have shown an obvious improvement post-treatment, and no severe adverse effects have been reported. Secukinumab is possibly an effective biological agent for PRP.Among the six types of PRP, type-VI PRP is most refractory to treatment, usually with a worse
A review on pityriasis rubra pilaris第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 63prognosis. But recently, Kranyak and Shuler [18] reported that a type-VI PRP patient, who had a history of hypertriglyceridemia, AST and ALT elevations and was prescribed with ixekizumab to treat PRP, had initially showed great clinical eff icacy wi th no s ignif icant adverse effects . Ixekizumab may be a biologic agent with potentially high efficacy in treating type-VI PRP.Risankizumab has been repor ted to have successfully treated a European male elderly who had a 15-months history of PRP. Recently, another IL-23p19 antagonist Guselkumab had shown a great response in treating a patient with PRP. Thus, IL-23 inhibitors might be a reliable biologic agent for some patients with PRP. However, not all PRP patients will show a good response when treated with risankizumab.6.4 PhototherapyPhototherapy is a controversial therapy for PRP. Both improvement and aggravation, have been reported in utilizing phototherapy especially narrow-band ultraviolent B (NB-UVB). As there are reports of photo aggravated PRP, it is recommended that pat ients with PRP should undergo photo provocation before receiving the NB-UVB therapy. A case report showed a patient with PRP, who was recalcitrant to oral isotretinoin, had received a complete resolution after treating with NB-UVB for 4 months. Recently, Massa et al. [19] demonstrated 90% improvement after implementing a total of 19 sessions and a cumulative dose of 10.5 J/cm2 NB-UVB in an 8-year-old Caucasian girl with mixed type-III/IV PRP. However, UVB may exacerbate PRP. Yaniv et al. [20] were the first to report a case of PRP exacerbated by UVB therapy, a 65-year-old woman with PRP developed a severe erythrodermic reaction after UVB therapy. Whether UVB therapy is effective to PRP patients is still controversial. In contrast, it is believed that systemic psoralens and ultraviolet A (PUVA) show little or no benefit in treating PRP. Since psoralens may worsen PRP, it was not recommended. However, some studies described a partial response on patients with PRP after receiving PUVA therapy.7. ConclusionPRP is a rare chronic inf lammatory skin disease characterized by scaling erythema, small hyperkeratotic follicular papules, and palmoplantar hyperkeratosis. PRP can be further divided into 6 types: Type-I/II are adult onset, Type-III/IV/ Ⅴ are juvenile onset, and type- Ⅵ is associated with HIV infection. The exact cause of PRP remains unknown, but it is believed that genetic mutation of CARD 14 gene, dysfunction in vitamin A metabolism, autoimmune disorder, endocrine disturbance, and infections, especially HIV infection may contribute to the pathogenesis of PRP. Each type of PRP has its own clinical features, supporting the diagnosis of PRP. Histopathologic examination is considered as the gold standard in the diagnosis of PRP, while dermoscopy is proposed to be a reliable diagnostic tool in recent years. Although there isn’t any U.S. FDA approved medication or algorithm for PRP treatment, combination therapy consisting of topical and systemic treatments is generally accepted as the first-line therapy for PRP. In most studies, oral retinoids are considered as the first-line systemic agent for both adults and children PRP patients, while in several studies, methotrexate is recommended as the first-line therapy for PRP patients. Along with the emergence of biologic agents and their high efficacy, good specificity, and considerable safety profile, biologic agents may become good alternatives to traditional systemic therapies in near future.
A review on pityriasis rubra pilaris澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal64Table 1. Proportion of different types of PRP proposed by Griffiths [1]Type Proportion of casesI. Classical adult 55%II. Atypical adult 5%III. Classical juvenile 10%IV. Circumscribed juvenile 25%V. Atypical juvenile 5%VI. HIV-related unknownTable 2. Clinical manifestations and prognosis of different types of PRP proposed by Griffiths [1]Type Clinical manifestations PrognosisI. Classical adult Red-orange papules and plaques with “islands of spar ing”, waxy palmoplantar keratoderma, cephalocaudal progressionspontaneous remission or even resolution within 3 yearsII. Atypical adult P r o l o n g e d c o u r s e , e c z e m a t o u s - l i k e l e s i o n s , ichthyosiform scale on lower extremities, coarse palmoplantar keratosis, alopeciaChronicIII. Classical juvenile Having similar manifestations to type-I PRP, but affects children in the first year or two of lifespontaneous resolut ion within a yearI V. C i r c u m s c r i b e d juvenilewell-demarcated group of hyperkeratotic follicular papules with an erythematous base predominantly on the knees and elbows, palmoplantar keratodermaUncertainV. Atypical juvenile Onset in infancy or early childhood, hyperkeratotic fo l l i cu la r papu les , i ch thyos i fo rm dermat i t i s , scleroderma-like changes on palms and solesChronicVI. HIV-related HIV positive, prominent follicular plugging with formation of spicules, acne conglobata, hidradenitis suppurativa, and lichen spinulosus. Erythroderma is a frequent complicationMostly chronicTable 3. Histopathologic findings in PRPStudy Histopathologic findingsF.F. Soeprono[8] hypergranulosis, neutrophils in the cornified layer, basket-weave cornified layer, thick suprapapillary plates, perivascular infiltrations, follicular hyperkeratotic plug, Zaouak et al. [9] irregular hyperkeratosis, parakeratosis, orthokeratosis, keratinous plugs, dilated hair folliclesKo et al. [10] checkerboard para- and orthokeratosis, follicular plugging, eosinophils, acantholysis, perifollicular parakeratosis, lichenoid infiltrate, hyperkeratosisHoover et al. [11] parakeratosis, orthokeratosis, basket-weave keratin, epidermal hyperplasia, thick suprapapillary plates, slight spongiosis, superficial perivascular infiltrate of lymphocytes, acantholysis Magro et al. [12] follicular plugging, epidermolytic hyperkeratosis, acantholytic dyskeratosis, hyperkeratosis, hyperplasia, vascular ectasia, eosinophils, neutrophils infiltration in stratum corneum, thickness changes in granular layer
A review on pityriasis rubra pilaris第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 65Figure 1. Figure 2.Figure 1,2. Plantar hyperkeratosis in a 56-year-old female PRP patient Figure 3.Figure 3. Waxy palmar hyperkeratosis in a 56-year-old female PRP patient8. References[1] Griff i ths WA. Pi tyr ias is rubra pi lar is . Clin Exp Dermatol. 1980;5(1):105-112. doi:10.1111/j.1365-2230. 1980.tb01676. x.[2] Gá l B , Göblös A , Dan i s J , e t a l . The management and genetic background of pityriasis rubra pilaris: a single-centre experience. J Eur Acad Dermatol Venereol. 2019;33(5):944-949. doi:10.1111/jdv.15455[3] Yu n C H , K i m J S , R y u H R , e t a l . Circumscribed juvenile pityriasis rubra pilaris responsive to alitretinoin. Dermatol Ther. 2016;29(2):81-83. doi:10.1111/dth.12320[4] Finzi AF, Altomare G, Bergamaschini L, Tucci A. Pityriasis rubra pilaris and and retinol-binding protein. Br J Dermatol. 1981;104(3):253-256. doi:10.1111/j.1365-2133. 1981.tb00946.x[5] Blauvelt A, Nahass GT, Pardo RJ, Kerdel FA . P i t y r i a s i s r u b r a p i l a r i s a n d H I V infection. J Am Acad Dermatol. 1991;24(5 P t 1 ) : 7 0 3 - 7 0 5 . d o i : 1 0 . 1 0 1 6 / 0 1 9 0 -9622(91)70106-c[6] Miralles ES, Núñez M, De Las Heras ME,
A review on pityriasis rubra pilaris澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal66Pérez B, Moreno R, Ledo A. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133(6):990-9 9 3 . d o i : 1 0 . 1111 / j . 1 3 6 5 - 2 1 3 3 . 1 9 9 5 .tb06939.x[7] All i son DS, El -Azhary RA, Calobr i s i SD, Dicken CH. Pityriasis rubra pilaris i n c h i l d r e n . J A m A c a d D e r m a t o l . 2002;47(3):386-389.[8] Soeprono FF. Histologic criteria for the diagnosis of pityriasis rubra pilaris. Am J Dermatopa tho l . 1986 ;8(4) :277-283 . doi:10.1097/00000372-198608000-00001[9] Zaouak A, Chamli A, Koubaa W, Hammami H, Fenniche S. Pityriasis rubra pilaris. Presse Med. 2019;48(6) :730-731. doi : 10.1016/j.lpm.2019.05.009[10] Ko CJ , Mi ls tone LM, Choi J , McNiff JM. Pityriasis rubra pilaris: the clinical context of acantholysis and other histologic features. Int J Dermatol. 2011;50(12):1480-1485. doi:10.1111/j.1365-4632.2011. 04990.x[11] H o o v e r W D J r , M a i z e J C . F o c a l a c a n t h o l y t i c d y s k e r a t o s i s o c c u r r i n g i n p i t y r i a s i s r u b r a p i l a r i s . A m J D e r m a t o p a t h o l . 1 9 9 0 ; 1 2 ( 3 ) : 3 2 1 - 3 2 3 . doi:10.1097/00000372-199006000-00060[12] Magro CM, Crowson AN. The clinical and histomorphological features of pityriasis rubra pilaris. A comparative analysis with psoriasis. J Cutan Pathol. 1997;24(7):416-424. doi:10.1111/j.1600-0560. 1997.tb00816.x[13] R o s s N A , C h u n g H J , L i Q , A n d r e w s JP, Keller MS, Uitto J. Epidemiologic, C l i n i c o p a t h o l o g i c , D i a g n o s t i c , a n d Management Challenges of Pityriasis Rubra Pilaris: A Case Series of 100 Patients. JAMA Dermatol. 2016;152(6):670-675. doi:10.1001/jamadermatol.2016.0091[14] Kettering C, Khosravi H, Ortiz C, English JC 3rd. Drug survival of systemic and b io log i c mono the rapy t r ea tmen t s fo r pityriasis rubra pilaris: A retrospective observational study. J Am Acad Dermatol. 2022 ;86(5 ) :1142-1143 . do i : 10 .1016 /j.jaad.2021.04.041[15] Kromer C, Sabat R, Celis D, Mössner R. Systemic therapies of pityriasis rubra pilaris: a systematic review. J Dtsch Dermatol Ges. 2019;17(3):243-259. doi:10.1111/ddg.13718[16] N a p o l i t a n o M , A b e n i D , D i d o n a B . B io log ic s fo r p i ty r i a s i s rub ra p i l a r i s treatment: A review of the literature. J Am Acad Dermatol. 2018;79(2):353-359.e11. doi: 10.1016/j.jaad.2018.03.036[17] Boudreaux BW, Pincelli TP, Bhullar PK, et al. Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis. Br J Dermato l . 2022;187(5) :650-658 . doi:10.1111/bjd.21708[18] Kranyak A, Shuler M. Pi tyriasis rubra pilaris rapidly cleared with ixekizumab in an HIV-positive patient. JAAD Case Rep. 2022; 27:55-57. Published 2022 Jul 20. doi: 10.1016/j.jdcr.2022.07.015[19] Massa AF, Vasconcelos P, Soares de Almeida L, Filipe P. Pityriasis rubra pilaris mixed type III/IV successfully treated with narrow band-ultraviolet B. Indian J Dermatol Venereol Leprol. 2015;81(4):435. doi:10.4103/0378-6323.156196[20] Yaniv R, Barzilai A, Trau H. Pityriasis rubra pilaris exacerbated by ultraviolet B p h o t o t h e r a p y . D e r m a t o l o g y . 1994;189(3):313. doi:10.1159/000246871
Un Kei CHAN et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 67Advances in the treatment and prevention of neonatal respiratory distress syndromeUn Kei CHAN*, Yi Lian YE AbstractNeonatal respiratory distress syndrome (NRDS) is a respiratory disease commonly observed in newborns, particularly in premature infants. It can cause breathing difficulties and, in severe cases, can be life-threatening. NRDS also increases the risk of complications in premature infants, which can lead to long-term neurodevelopmental and cognitive impairments, affecting children’s intelligence and learning ability. As a result, early diagnosis and treatment of NRDS are crucial to improving the survival rate of affected infants, reducing the incidence of complications, and enhancing children’s health while alleviating medical burden.This article aims to provide clinicians with a comprehensive reference for the prevention and treatment of NRDS, covering the concepts, diagnosis, and prevention of NRDS, indications for pulmonary surfactant replacement therapy, administration methods, and selection and application of respiratory support technology.Keywords: Neonatal respiratory distress syndrome; Prevention; Pulmonary surfactant replacement; Respiratory supportKiang Wu Hospital*Correspondence to: Yi Lian YE, yeyilian@yahoo.com.hk1. IntroductionNeonatal Respira tory Dis t ress Syndrome (NRDS) is a common respiratory disease in newborns, particularly in premature infants. With the increasing global rate of premature births, the incidence of NRDS has also increased. According to the World Health Organization (WHO) data in 2019, the global rate of premature births is about 10.6%, while the rate in China is about 6.9% [1]. Although the survival rate of premature infants has improved due to advancements in perinatal medicine and neonatal resuscitation, the high incidence and mortality rates of NRDS still require significant attention. This article aims to review and discuss the best practices for the treatment and prevention of NRDS, in order to improve the effectiveness and safety of clinical practice and provide better protection for the health of NRDS patients.2. The concept of NRDSSufficient surfactant is required for the alveoli to remain open and maintain adequate surface tension. Surfactant is a mixture of proteins and lipids synthesized by type II alveolar cells in the late fetal development. It reduces surface tension in the alveoli, allowing the lung tissue to expand fully and maintain respiratory function. Surfactant production increases rapidly in late pregnancy. The smaller the gestational age, the more pronounced the deficiency of surfactant. In such cases, the lack of surfactant can cause the alveoli collapse, impairing air exchange and making breathing difficult. Neonates show progressive dyspnea, which can even be life-threatening. Other factors, such as maternal smoking, preeclampsia, placental dysfunction or abruption, and fetal hypoxia, may also increase the risk of NRDS.
Advances in the treatment and prevention of neonatal respiratory distress syndrome澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal68In addition to causing respiratory distress, NRDS can increase the risk of complications in premature infants, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage ( IVH), and necro t iz ing enterocol i t i s (NEC) . Fu r the rmore , NRDS may l ead t o l ong - t e rm developmental impairment of the nervous system and cogni t ive funct ion, which can affect the intelligence and learning ability of children [2]. Therefore, early diagnosis and treatment of NRDS are very important to improve the survival rate of affected infants and reducing the incidence of complications.2.1 Diagnosis of NRDSThe diagnosis of NRDS is based on progressive resp i ra tory d i s t ress and charac te r i s t ic ches t X-ray findings in premature infants after birth. Progressive respiratory distress, which can present as tachypnea, intercostal retractions, grunting sounds, frothy secretions, moaning, and decreased oxygen saturation. In severe cases, the infant may experience cyanosis, apnea and respiratory failure. These symptoms usually occur shortly after birth and tend to worsen over time. Chest X-ray findings include low lung volume, diffuse granular or ground-glass opacities, and air bronchograms. These opacities may be patchy or diffuse. The lung fields may appear homogeneously white, and the heart border may be difficult to visualize due to lung opacification[3]. Lung ul trasonography (LUS) has become increasingly useful in the diagnosis and monitoring of NRDS. The primary LUS features of NRDS i n c l u d e b i l a t e r a l w h i t e l u n g , p l e u r a l l i n e abnormalities, and consolidation. LUS is a non-invasive and rapid method for evaluating lung pathology. The results of the meta-analysis by Jiang et al. showed that LUS has high diagnostic value for NRDS. Hai et al found that the simultaneous presence of lung consolidation, abnormal pleural line, and bilateral white lungs or absence of lung consolidation, abnormal pleural line, and absence of A-lines was 100% sensitive and specific for predicting NRDS. Lung consolidation is the most important and specific feature of NRDS. However, LUS may miss pneumothorax, pneumomediastinum, or pneumopericardium. Therefore, for newborns wi th suspec ted NRDS, CXR i s r equ i red fo r identification. LUS can complement CXR in the diagnosis and follow-up monitoring of NRDS, thereby reducing radiation exposure[4].2.2 Treatment of NRDSThe treatment strategies for NRDS mainly inc lude p reven t ive in te rven t ion , pu lmonary surfactant replacement, respiratory support, fluid and electrolyte balance, and nutritional support. The goal is to maintain good respiratory function and reduce the risk of complications.3. Preventative interventionsPrematurity is significant risk factors for NRDS, and preventive interventions can reduce the risk of prematurity and thus decrease the occurrence of NRDS. These preventive interventions include antenatal care and prenatal corticosteroid therapy.Antenatal care measures include good prenatal health management, regular prenatal care, control of chronic diseases such as gestational diabetes and hypertension, avoidance of smoking and alcohol consumption, and following medical advice. These measures can reduce the risk of prematurity and thus decrease the occurrence of NRDS.For premature infants who cannot be prevented, prena ta l cor t icos te ro id therapy can promote fe ta l lung maturat ion, increase the synthesis and release of pulmonary surfactant, improve neonatal lung function, and reduce the incidence of NRDS and its related complications. A Cochrane review by McGoldrick et al. in 2020 found that prenatal corticosteroids significantly reduced the incidence of NRDS, mortality, and other neonatal complications in extremely low birth weight preterm infants. Multiple doses within the same gestational week were found to be more effective than a single dose [5]. The European Consensus Guidelines on the Management of Respiratory Distress Syndrome,
Advances in the treatment and prevention of neonatal respiratory distress syndrome第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 69published by Sweet et al. in 2019, recommended that all pregnant women at risk of preterm delivery receive prenatal corticosteroid therapy between 24 and 34 weeks of gestation, unless contraindicated due to factors such as hypersensitivity to any component of the formulation, tuberculosis, and acute chorioamnionitis. It is important to note that antenatal corticosteroid therapy did not increase the risk of adverse effects, including birth defects and neurodevelopmental abnormalities in preterm infants [6] . However, safe ty and eff icacy in premature infants and pregnant women need to be closely monitored during treatment to ensure maximum clinical benefit.4. Pulmonary surfactant replacement therapyPulmonary surfactant replacement therapy is effective in preventing and treating NRDS. The most common types of exogenous pulmonary surfactants used are artificially prepared. These preparations can be either natural or synthetic, with natural surfactants obtained from lung lavage fluid or chopped lung tissue from animals. Studies have shown that natural surfactants are superior to synthetic ones in terms of efficacy.The updated European Consensus Guidelines in 2019 recommend ea r ly admin i s t ra t ion o f pulmonary surfactant therapy in premature infants to reduce the incidence of NRDS [6]. Pulmonary surfactant therapy can effect ively reduce the occurrence and severi ty of NRDS in preterm infants and lower the risk of related complications such as bronchopulmonary dysplas ia (BPD), pulmonary emphysema, and pneumothorax. This therapy is particularly beneficial for extremely premature in fan ts (<28 weeks) . I f an in fan t continues to experience respiratory distress and requires FiO2>0.3 to maintain SpO2>90% after initial respiratory support, pulmonary surfactant administration should be considered. Studies have shown that administration 2 hours after birth is most effective and associated with a lower risk of BPD and pulmonary air leaks.Repea ted admin i s t r a t ion i s an e ffec t ive treatment strategy if oxygen demand remains high above the predetermined FiO2 threshold, such as requiring FiO2≥0.30 to maintain SpO2>90%, additional doses pulmonary surfactant should be considered. Compared to a single dose, repeated administration reduces mortality and morbidity in preterm infants born before 30 weeks with RDS. For infants requiring repeated administration, surfactant can be administered at most once every 12 hours and up to 3-4 times within 48 hours[7].Cur ren t ly, the re a re var ious methods o f administration available for pulmonary surfactant therapy, including traditional InSurE (intubation, surfactant administration, and extubation) technique and minimally invasive techniques such as MIST (minimally invasive surfactant therapy) and LISA (less invasive surfactant administration). The InSurE procedure is to instill pulmonary s u r f a c t a n t t h r o u g h a s m a l l c a t h e t e r a f t e r endotracheal intubation, followed by posit ive p r e s s u r e v e n t i l a t i o n . M I S T a n d L I S A a r e administering surfactant through a thin endotracheal catheter under positive nasal pressure ventilation. Recent studies have shown that administering surfactant via a thin catheter reduces the risk of death or BPD, as well as the incidence of intubation and major complications, compared to intubation administration [8]. A meta-analysis in 2021 included 16 studies comparing surfactant administration via thin catheter with endotracheal intubation (ETT). Conclusions: Surfactant administration via a thin catheter was associated with a lower risk of death or BPD, fewer intubations in the first 72 hours, and lower rates of major complications and in-hospital mortality compared with administration via ETT [8]. Bhupendra et al.’s study compared the efficacy of non-invasive positive pressure ventilation-assisted surfactant administrat ion (NIPPV-SURF) and traditional InSurE on RDS premature infants at 28 to 34 weeks. The results showed that fewer infants in the NIPPV-SURF group required mechanical
Advances in the treatment and prevention of neonatal respiratory distress syndrome澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal70ventilation and endotracheal intubation and had significantly shorter hospital stays than those in the InSurE group. Minimally invasive surfactant therapy techniques also include surfactant nebulization and laryngeal mask-assisted administration[9].Pulmonary surfactant therapy carries potential complications. The extraction of surfactant from animal sources poses a risk of immune activation in certain cases. In rare instances, administration of the drug can lead to pneumothorax and/or pulmonary hemorrhage. Other possible side effects include intraventricular hemorrhage, patent ductus arteriosus, retinopathy, necrotizing enterocolitis, and blockage of the endotracheal tube etc [10].5. Respiratory supportRespiratory support is the key to the treatment of NRDS, mainly including non-invasive respiratory support and invasive respiratory support . For infants with regular breathing and suff ic ient respiratory effort, noninvasive respiratory support such as nasal continuous positive airway pressure (nCPAP) and nasal intermittent positive pressure vent i la t ion (NIPPV) are preferred, and these methods have been shown to reduce the duration of mechanical ventilation and lower the incidence of bronchopulmonary dysplasia (BPD). For infants with frequent apnea, dyspnea or worsening condition after noninvasive respiratory support, invasive mechanical ventilation support is necessary. However, invasive ventilation can lead to respiratory machine-related pressure injuries, infections and other complications, and should be used as a secondary option with close monitoring and management of complications when necessary [11].5.1 Non-invasive respiratory supportNon-invasive respiratory support methods include nCPAP, NIPPV, High-flow nasal cannula (HFNC), and Nasal high-frequency oscillatory ventilation (nHFOV).5.2 nCPAP and NIPPVnCPAP provides constant positive pressure (PEEP) to the lungs of newborns through different nasal interfaces. PEEP can effectively support respiratory failure, maintain functional residual capacity, reduce airway collapse, and facilitate gas exchange. NIPPV is an alternative strategy to nCPAP that provides timed positive pressure ventilation above the PEEP level. There are two NIPPV delivery modes: bilevel NIPPV and conventional mechanical ventilator-driven NIPPV (CMV-NIPPV). Bilevel NIPPV provides two alternating PEEP levels, al lowing infants to breathe spontaneously. In contrast, CMV-NIPPV uses higher peak inspiratory pressure and shorter inspiratory t ime. NIPPV maintains functional residual capacity through intermittent positive pressure, improves lung re-expansion, reduces respiratory effort, improves synchrony, and reduces pulmonary inflammation. Both nCPAP and NIPPV may cause complications such as nasal trauma, feeding intolerance, and pneumothorax.NIPPV may be slightly superior to nCPAP for initial respiratory support, but nCPAP has lower equipment requirements and is more easily accessible in clinical practice. Therefore, nCPAP is recommended for initial respiratory support. For preterm infants with established NRDS but without respiratory failure, nCPAP is the first choice. Compared to invasive mechanical ventilation, nCPAP group has a lower risk of BPD, lower mortality rates, and fewer complications [12].5.3 HFNCHFNC delivers heated and humidified air at flow rates of up to 8L/min through small nasal tubes. Creates a flow-dependent variable inflation pressure, provides PEEP, reduces respiratory effort, while minimizing the risk of nasal trauma. However, the pressure generated by HFNC cannot be measured in cl inical pract ice. The airway pressure varies greatly and is difficult to monitor. The evidence for i ts use as initial respiratory suppor t or pr imary respi ra tory suppor t a f ter extubation in RDS infants is limited, and the failure rate is high. Therefore, it is not recommended as the first-line treatment modality for RDS [13].
Advances in the treatment and prevention of neonatal respiratory distress syndrome第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 715.4 nHFOVnHFOV delivers high-frequency oscillatory a i r f low through the nasal cavi ty to maintain functional residual capacity and facilitate gas exchange in the lungs. Studies by Xing-Wang and Jie have found that nHFOV reduces the need for invasive mechanical ventilation in premature infants with RDS compared to nCPAP, with no increase in adverse effects [14]. Ramin et al. also showed that nHFOV significantly shortens the duration of noninvasive respiratory support and reduces the need for intubation compared to nCPAP. In addition, nHFOV appears to reduce the incidence of IVH without increasing other complications. nHFOV can reduce lung injury and respiratory failure, improve oxygenation, and lower carbon dioxide levels. However, it requires more complex equipment and is not widely used in clinical practice [15].5.5 Invasive respiratory supportIn terms of invasive respiratory support , traditional pressure-limited ventilation (PLV) has been used, but in recent years, volume-targeted ventilation (VTV) has been widely applied. Among them, volume guarantee venti lat ion (VGV) is a ventilation mode that has been studied more in recent years. Compared to PLV, VGV adapts to changes in the patient’s respiratory volume, providing consistent tidal volume regardless of changes in compliance or resistance. This approach aims to protect the lungs, reduce lung damage, lower mortality rates, and decrease the incidence of respiratory pauses and respiratory failure. It appears to provide better clinical outcomes in extremely premature infants [16].6. Oxygen therapyNo matter what kind of respiratory support is chosen, premature infants require supplemental oxygen to maintain peripheral oxygen saturation within a target range. However, excessive oxygen therapy can lead to oxygen toxicity, causing harm to infants, especially premature infants. The ideal oxygen saturation level still needs to be explored. However, there is evidence to suggest that lower oxygen saturation levels (85-89%) can reduce the risk of severe retinopathy of prematurity (ROP), but at the cost of increased mortality and incidence of necrotizing enterocolitis (NEC). Therefore, it is still recommended to target oxygen saturation levels between 90% to 94%. Physicians need to adjust the oxygen concentration according to the infant’s oxygenation level to avoid the risk of oxygen toxicity [17].7. Fluid balancePremature infants often have patent ductus arteriosus (PDA), and excessive fluid intake should be avoided to prevent interference with PDA closure. Additionally, excessive fluid intake is also associated with necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). Mild fluid restriction is often implemented for premature infants with NRDS in clinical practice. Additionally, it is important to maintain an appropriate ambient temperature for infants to reduce heat loss and maintain core body temperature within the normal r ange , the reby reduc ing oxygen and energy consumption [18].8. Nutrit ional supportNutr i t ional suppor t i s another impor tant aspect of NRDS treatment. Energy supply must meet both metabolic consumption and growth requirements. Premature infants with NRDS may require parenteral nutrition to meet their calorie and nutritional needs [18].9. CaffeineIt is commonly used in the treatment of apnea in premature infants. For extremely premature (EPT, gestational age <28 weeks) infants, caffeine should be given early to enhance breathing drive, reduce the risk of apnea, and reduce the need for respiratory support therapy. Current evidence supports the initiation of caffeine within the first 10 days of life as one of the few pharmacotherapies proven to prevent the development of BPD [19]
Advances in the treatment and prevention of neonatal respiratory distress syndrome澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal7210. Family supportFamily support is critical for NRDS treatment and recovery in preterm infants. Families should be involved in baby’s care, understand the special needs of them, and seek professional help and support.11. Complications of NRDSBronchopulmonary dysplasia (BPD) is a major chronic complication of RDS. Although treatment techniques for RDS have improved, the incidence of BPD remains high. BPD is caused by a variety of factors, including volume trauma, barotrauma, oxygen toxicity, or inflammation from infection. The immaturity of lung structure and function in preterm infants can exacerbate these effects.According to a Cochrane review of 11 trials, intramuscular vitamin A has a small benefit for reducing the risk of BPD in VLBW infants. A randomized controlled trial compared the effects of enteral and intramuscular vitamin A supplementation in 188 infants born at less than 28 weeks of gestation. The results showed that enteral supplementation with water-soluble vitamin A could improve plasma retinol levels in extremely premature infants but did not reduce the severity of BPD. Given these data and the need for frequent intramuscular injections, vitamin A has not been widely used.Some complications were caused by therapeutic interventions, including endotracheal intubation, supplemental oxygen, and positive pressure ventilation. Compl ica t ions assoc ia ted wi th endot rachea l intubation are common, with the most common being displacement or misplacement of the tube, leading to unilateral lung ventilation, resulting in pneumothorax and contralateral lung collapse. Other complications of intubation include subglottic stenosis, esophageal and pharyngeal perforation, etc. [20].12. Our cl inical applicationsIn our unit, prophylactic prenatal corticosteroid therapy is administered to pregnant women at risk of preterm delivery before 34 weeks of gestation.For premature infants after birth, particularly for very premature infants (≤ 32 weeks gestational age), we provide early positive pressure ventilation to prevent and reduce lung collapse, improve oxygenation, and mitigate the risk of respiratory distress syndrome (RDS). The choice of subsequent respiratory support is determined based on the infant’s initial recovery. Non-invasive positive p ressure ven t i l a t ion methods such as Nasa l Continuous Positive Airway Pressure (nCPAP) and Nasal Intermittent Positive Pressure Ventilation (NIPPV) are preferred for infants showing strong and regular respiratory efforts. Based on literature reports and our recent experience, NIPPV has demonstrated greater effectiveness, leading us to prioritize its initial use for respiratory support. Additionally, if nCPAP proves ineffective, we promptly transition to NIPPV.For infants wi th poor in i t ia l response to resuscitation, severe dyspnea, or frequent apneas, we provide immediate invasive support through endotracheal intubation. The pressure settings are primarily adjusted based on tidal volume and the extent of lung expansion shown on chest X-ray.Regarding extremely premature infants (<28 weeks gestational age), the literature recommends early administration of pulmonary surfactant and prophylactic caffeine therapy. However, due to the limited number of cases we encounter, we currently lack a standardized protocol for prophylactic treatment in extremely premature infants group. Clinical decisions are primarily made based on the individual circumstances of the infants.If respiratory distress persists or if the infant requires a high oxygen concentration (eg. FiO2 ≥ 40%) to maintain adequate oxygenation after initial support, we consider the administration of pulmonary surfactant. We use Curosurf (porcine-derived exogenous pulmonary surfactant) and prefer the less invasive surfactant administration technique (LISA) under non-invasive ventilation. Our experience with LISA over the past three years has shown good efficacy.
Advances in the treatment and prevention of neonatal respiratory distress syndrome第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 7313. ConclusionN R D S i s o n e o f t h e m o s t c o m m o n respiratory problems in premature infants and a significant cause of multiple complications. It has a serious impact on the survival and health of newborns. Therefore, effective prevention and treatment strategies are crucial. Antenatal use of corticosteroids and replacement of pulmonary surfactant are effective strategies for preventing and treating NRDS. Non-invasive ventilation methods such as nCPAP and NIPPV are preferred respiratory support methods. Additionally, fluid and electrolyte balance and nutritional support are also important factors in the treatment of NRDS.However, some challenges and controversies remain. For example, for extremely low birth weight infants, how to balance the risk of retinopathy and brain disease with early respiratory support and oxygen therapy still needs more research to solve. In addition, the optimal timing, dose, and mode of administration of pulmonary surfactant are controversial.In addition to existing treatment, there are several new treatments that are being researched and explored. For example, extracellular vesicles derived from mesenchymal stem cells (MSCs) have been shown to promote regeneration and immune regulation, improve lung morphology and function, and suppress inflammation in animal models, making them a potential option for treating NRDS. Additionally, insulin-like growth factor-1 (IGF-1) is also considered a potential target for treating BPD, improving treatment outcomes by enhancing vascular development.In the process of treating NRDS, it is necessary to choose the most suitable treatment plan based on the patient’s specific condition, while also paying attention to the potential side effects and risks of treatment. Overall, NRDS treatment still faces various challenges and difficulties, but through continuous research and exploration, it is believed that more effective treatment strategies will emerge in the future.14. References[1] World Health Organization. (2018). Preterm birth. Fact sheet. [Internet] Retrieved from https://www.who.int/news-room/fact-sheets/detail/preterm-birth[2] Tobias M, Dirk B, Manuel B. Evidence for the Management of Bronchopulmonary D y s p l a s i a i n Ve r y P r e t e r m I n f a n t s . Children J 2021;8(4),298.doi.org/10.3390/children8040298[3] Hiles M, Culpan A, Watts C, et al. Neonatal respiratory distress syndrome: Chest X-ray or lung ultrasound? A systematic review. Ul t rasound J 2017;25(2) : 80–91. do i : 10.1177/1742271X16689374[4] HaiRan M, Jing L, Wen-Kang Y. Diagnostic va lue of lung u l t rasound for neonata l respiratory distress syndrome: a meta-analysis and systematic review. Medical Ultrasonography J 2020;22(3): 325-333. doi: 10.11152/mu-2485[5] McGoldrick E, Stewart F, Parker R, et al. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of systematic reviews J 2020(12):CD004454. doi: 10.1002/14651858.CD004454.pub4[6] Sweet D, Carnielli V, Greisen Gorm, et al . European Consensus Guidelines on the management of respiratory distress syndrome: 2022 update. Neonatology J 2023;120(1): 3-23. doi: 10.1159/000528914[7] Vi r a r a g h a v a n R , Ta p a s B , T h a n g a r a j A, e t a l . Cl in ica l dec is ion thresholds for surfactant administration in preterm infants: a systematic review and network m e t a a n a l y s i s . e C l i n i c a l M e d i c i n e J 2 0 2 3 ; 6 2 : 1 0 2 0 9 7 . d o i : 1 0 . 1 0 1 6 /j.eclinm.2023.102097[8] Mohamed E , Pe t e r G , Kev in I , e t a l . Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory
Advances in the treatment and prevention of neonatal respiratory distress syndrome澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal74distress syndrome. Cochrane Database of systematic reviews J 2021;2021(5): C D 0 11 6 7 2 . d o i : 1 0 . 1 0 0 2 / 1 4 6 5 1 8 5 8 .CD011672.pub2[9] Bhupendra K, Anindya K, Suchandra M, et al. Minimally invasive surfactant therapy versus InSurE in pre term neonates of 28 to 34 weeks with respiratory distress syndrome on non-invasive positive pressure v e n t i l a t i o n - a r a n d o m i z e d c o n t r o l l e d tr ial . European Journal of Pediatr ics J 2020;179(8) :1287-1293. doi : 10.1007/s00431-020-03682-9[10] H i n a K , K o m a l M . S u r f a c t a n t . S t a t P e a r l s [ I n t e r n e t ] L a s t U p d a t e : June 12, 2023.Retr ieved f rom ht tps : / /w w w . n c b i . n l m . n i h . g o v / b o o k s /NBK546600/#:~:text=Adverse%20Effects,-The%20usage%20of&tex t=Rare ly%20t h e % 2 0 d r u g % 2 0 c a n % 2 0 l e a d , c a n % 2 0cause%20complications%20as%20well[11] Ourania K, Theodore D, Anne G. Neonatal respiratory support strategies―short and long-term respiratory outcomes. Front Pediatr J 2023; 11: 1212074. doi: 10.3389/fped.2023.1212074[12] Viraraghavan V, Kiran M, Charles C, et al. Efficacy of noninvasive respiratory support modes for primary respiratory support in preterm neonates with respiratory distress syndrome: Systematic review and network meta-analysis. Pediatric Pulmonology J 2020;55(11):2940-2963. doi : 10.1002/ppul.25011[13] Judith B, Brigitte L, Christoph C, et al. Non-Invasive Ventilation in Neonatology. D e u t s c h e s A r z t e b l a t t I n t e r n a t i o n a l J 2019;116(11) : 177-183. doi : 10 .3238/arztebl.2019.0177[14] J i e L , L o n g C , Yu a n S . N a s a l h i g h -frequency oscillatory ventilation versus nasal continuous positive airway pressure as primary respiratory support strategies for respiratory distress syndrome in preterm infants: a systematic review and meta-analysis. European Journal of Pediatrics J 2022; 181(1):215-223. doi: 10.1007/s00431-021-04190-0[15] Ramin I, Amir A, Ahmad A, et al. Nasal h igh-frequency osci l la tory vent i la t ion (nHFOV) versus nasal continuous positive airway pressure (NCPAP) as an ini t ial therapy for respiratory distress syndrome (RDS) in preterm and near-term infants. B M J P a e d i a t r i c s O p e n J 2 0 1 9 ; 3 ( 1 ) : e000443. doi: 10.1136/bmjpo-2019-000443[16] Milenka C, Joseph H, Dajana S. Volume-guarantee vs. pressure-limited ventilation in evolving bronchopulmonary dysplasia. Front Pediatric J 2022;10: 952376. doi: 10.3389/fped.2022.952376[17] Perrone S, Bracciali C, Virgilio N, et al. Oxygen use in neonatal care: A two-edged sword. Front iers in Pediatr ics J 2017. doi:10.3389/fped.2018.00143[18] Yadav D, Walker A, Behrsin J. Respiratory d i s t r e s s syndrome – neona te s a t r i sk UHL Neonatal Guideline. Approved by: Neonatal Guidelines Group and Neonatal GovernanceGroup Trust Ref: C32/2018. [Internet] Retrieved from https://secure.library.leicestershospitals.nhs.uk/PAGL/Shared%20Documents/Respiratory%20D i s t r e s s % 2 0 S y n d r o m e % 2 0 - % 2 0Neona te s%20a t%20Risk%20UHL%20Neonatal%20Guideline.pdf[19] Laura M, Sanja Z, Caroline H, et al. Caffeine in preterm infants: where are we in 2020? ERJ Open Res J 2020 Jan; 6(1): 00330-2019. doi: 10.1183/23120541.00330-2019[20] Hennelly M, Greenberg R, Aleem S. An Update on the Prevention and Management of Bronchopulmonary Dysplasia. Pediatric Hea l th , Med ic ine and Therapeu t i c s J 2021;12:405-419. doi: 10.2147/PHMT.S287693
Cheong U KUOK et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 75Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repairCheong U KUOK1*, Gang Zhu LIANG 2, Chon Man IEONG 1AbstractThree patients suffered endoleaks after thoracic endovascular aortic repair (TEVAR). The type 1 endoleak were treated by direct transcutaneous puncture embolization (DTPE) after failure of conventional endovascular methods of repair. The type 2 endoleak was treated initially by DTPE in a symptomatic patient with expansion of the aneurysmal sac after conservative observation. Coils and/or Onyx copolymer were used as embolic agents for DTPE. A technically successful repair of the endoleak was accomplished in all three patients. Keywords: Thoracic Aorta; Endoleak; Endovascular Repair; Therapeutic Embolization1Department of Radiology, Conde de São Januário General hospital, Macao, China2Department of Vascular Surgery, Conde de São Januário General hospital, Macao, China*Correspondence to: Cheong U KUOK, kuokCU@gamil.com1. IntroductionNowadays , TEVAR is a wel l -es tabl ished technique for thoracic aortic aneurysm (TAA) or thoracic aortic dissection (TAD) treatment, and it has been proven to be safe and effective over two decades of experience [1]. However, the endoleak is a potential complication which may indicate persistent systemic pressurization of aneurysm sac and possibly causes sac enlargement or rupture. It is reported that the rate of endoleak after TEVAR is as high as 9-38 % [2-4] and endoleak represents the most frequent cause of reintervention (15-20%) after TEVAR [5,6]. Type 1 endo leak cou ld be co r r ec t ed by attachment site securement including transarterial embolization of endoleak via the endoleak channels or lengthen the proximal graft landing zone to seal the endoleak. Type 2 endoleak may be managed conservatively with serial computed tomography angiography (CTA) follow up. DTPE was described in some case reports as a “bailout” method for failed type 1 and type 2 endoleak repair [7-14]. With regards to this, we present our experience with DTPE for aneurysm sac embolization in 2 type 1a endoleak patients after failed conventional endovascular methods repair and 1 patient with type 2 endoleak presented with persistent chest pain and aneurysm sac expanding after serial CTA observation.2. Materials and methods Between July 2012 and May 2019, DTPE was attempted in three patients with endoleaks after TEVAR. Patient 1# was an 89 year-old male who suffered from thoracic aortic aneurysm and underwent TEVAR with left subclavian artery chimney stenting. Type 1a endoleak was found post-operation and the aneurysm sac size was increased during follow up. Transartery coils embolization was performed but the remarkably
Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repair澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal76enlarged aneurysm sac was found during follow up. Patient 2# was a 67 year-old female who suffered ruptured aortic arch pseudoaneurysm and urgent carotid to carotid bypass together with TEVAR were performed. Repeated CT scan found type 1a endoleak and expanded aneurysm sac. Patient 3# was a 64-year-old female who suffered from aortic arch aneurysm and underwent aortic arch total debranching combined with TEVAR. Type 2 endoleak was confirmed by CT scan after operation. She complained of persistent chest pain and type 2 endoleak with aneurysm sac expanding was revealed by serial CTA follow-up (Figure 1a and Figure 1b). DTPE was then utilized as a “bail-out” method for endoleak repair in all 3 cases.The procedures were performed in hybrid opera t ion room where cone-beam computed t o m o g r a p h y ( C B C T ) w a s a v a i l a b l e . Tr a n s -parasternal route was applied in Patient 1# and trans-paraspinal route was applied in Patient 2#and Patient 3#. All procedures were performed under local anesthesia. The needle puncture site and advance route was chosen by careful evaluation according to aneurysm sac location, endoleak site and anatomical structure from CT scan. Under CT/3D navigation guidance, a 18G needle co-axis with a 21G Chiba needle directly punctured into the leakage sac. CT was used to assure the right direction of the needle to the endoleak sac and avoidance of pulmonary parenchyma and esophagus injury (Figure 2a and 2b, Patient 3#). Successful puncture of the endoleak sac was confirmed by backflow of blood from the needle and by sacography in which the endoleak could be clearly visualized (Figure 2c, Patient 3#). Under fluoroscopic monitor, a microcatheter was exchanged for embolization procedure, metallic coils and/or certain amount of Onyx copolymer (EV3, Irvine-CA) was injected into the leakage sac for complete embolization. The injection was ceased after the endoleak sac was just full of Onyx without overflow out of the sac. After embolization, sacography was repeated to confirm the absence of the endoleak channel after the procedure. CT was performed again after the coaxial needle was removed to identify any pneumothorax or hematoma. The hemostasis of the puncture site was achieved by manual compression.3. ResultsBaseline demographics, aortic lesion types, procedural outcomes, in-hospital complications as well as follow-up evaluations in the 3 patients are summarized in Table 1. Diminished type 1a endoleak and shrunk aneurysm sac was observed by repeated CT scan in Patient 1# without any symptom presented. Successful endoleak repairs were achieved and confirmed by repeated CT scan for Patient 2# and Patient 3#. Patient 1# died from acute myocardial infarction 7 months after DTPE procedure. Patient2# died 1 month after the procedure due to pneumonia. Patient 3# was followed for 9 years and no endoleak was found by serial CTA (Figure 3) and she continued to be asymptomatic. No access related complications were encountered in all 3 patients.
Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repair第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 77Figure 1a. Figure 1b.Figure 1a and Figure 1b (Patient 3#). A 64-year-old female suffered from aortic arch aneurysm and underwent aortic arch total debranching combined with TEVAR. She complained persistent chest pain and type 2 endoleak with aneurysm sac expanding was revealed by serial CTA.Figure 2a. Figure 2b. Figure 2c.Figure 2. Under CT/3D navigation guidance, an 18G needle positioned co-axially with a 21G Chiba needle was inserted directly into the aneurysmal sac. CT was used to assure the correct navigation of the needle into the endoleak sac to avoid injury to the pulmonary parenchyma and esophagus (Figure 2a and 2b). Successful puncture of the endoleak sac was confirmed by backflow of blood from the needle and by sacography in which the endoleak could be visualized (Figure 2c).Figure 3.Figure 3. Follow up CTA revealed no endoleak was noted with aneurysm sac shrink and the patient keep asymptomatic.
Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repair澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal78Table 1. Patient demographics, clinical characteristics and outcomesPatient No.1 No. 2 No. 3Age 89 67 64gender Male Female FemaleConcomitant diseaseHypertension Y Y YDiabetes mellitus N Y NHyperlipidemia Y N NCoronary artery disease Y N NCerebrovascular disease N N NAortic lesion type Aortic arch aneurysm Aortic arch ruptured pseudo-aneurysmAortic arch aneurysmEndoleak type Ia Ia IIPuncture route Tans-parasternal Tans-paraspinal Tans-paraspinalEmbolization material Onyx metallic coils and Onyx OnyxTreatment result Endoleak diminished with aneurysm sac shrink Endoleak Successfully RepairedEndoleak Successfully RepairedComplications None None NoneFollow-up evaluations Died 7 months after DTPE due to cardiac attackDied 1 month after the procedure due to pneumoniaFollowed up for 9 years and no endoleak was found by serial CTATable 2. Published Studies of DTPEYear and AuthorEndoleak Type(number) Route EmbolizationMterial Result and complications2007Riesenman Type 1A (1) Tans-paraspinal RoutePlatinum Nester Coils, 1:3 Mixture of Trufill Glue and Ethiodol Bilateral Lower-extremity ParaparesisAortoesophageal FistulaEndograft InfectionDeath2009Stavropoulos Type 1A (1) Transgress Pleura and LungPlatinum Coils, NCBA Endoleak Successfully Repaired2011Seth Klein Type 2 (1) Tans-paraspinal RouteEthiodol and NCBA Endoleak Successfully Repaired2012Mussa Type 2 (1) Tans-paraspinal RoutePlatinum Coils, Ethiodol and NCBA Endoleak Successfully Repaired2013Katada Type 2 (2) NA Ethiodol and NCBA Endoleak Successfully Repaired2013Kreusch Type 2 (1) Tans-paraspinal RouteTornado Microcoils,Gelfoam Mixed in Contrast Medium, Thrombin Endoleak Successfully RepairedPeriaortic Hematoma(Resolution During Follow Up)2014Bangard Type 1A (1) Tans-parasternal RouteMechanically Detachable CoilsSuperinfection of the Pseudoaneurysm (Recovered by Antibiotics)Endoleak Successfully Repaired2015Katada Type 1A (1) NAInterlocking Metal Coils,Ethiodol and NCBAEndoleak Successfully Repaired
Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repair第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 794. DiscussionFrom 2007 to present, eight published articles demonstrated nine cases of type 1 and type 2 endoleak after TEVAR who were treated by DTPE. The endoleak nature, puncture route, embolization material, treatment results and complications of the published cases were summarized in Table 2[7-14]. In this case report study we presented three cases with type 1a and type 2 endoleaks after TEVAR who were successfully treated by DTPE. Conventionally, type 1 endoleak could be corrected by securing the graft attachment sites by balloon angioplasty of the endograft or placement of a balloon-expandable bare-metal stent to provide a radial force at the attachment site. Trans-arterial embolization of endoleak via the endoleak channels could be utilized as well. Deployment of extension endograft component may need some combined techniques (aortic arch debranching, parallel stents or fenestrated stents) to reconstruct the artic arch branch arteries. DTPE is usually chosen as a “bail-out” method for some cases which failed to achieve successful repairment of type 1 endoleak upon these conventional means. Type 2 endoleak may be managed conservatively with serial computed t o m o g r a p h y a n g i o g r a p h y ( C TA ) f o l l o w - u p . Intervention for type 2 endoleak is recommended for persistent endoleak with aneurysm sac expansion. Transcatheter embolization via collateral vessels is the most common intervention for type 2 endoleak after stent-graft repairs in the abdominal aorta. However, treatment of type 2 thoracic endoleak poses a greater challenge than the treatment of type 2 abdominal endoleak. The collateral circulation in the chest involving the thoracic aorta is not as well developed as the collateral vessels in the abdomen, making transarterial embolization of thoracic endoleak rather formidable. Furthermore, the embolization procedure via collateral vessels is not always possible if the stent-graft spans one or more of the major aortic branches proximally or distally. [11] Therefore, DTPE is often necessary for type 2 endoleak after thoracic stent-graft repairs when conservatively observation failed.DTPE is a very challenging method due to its complexity of transthoracic puncture procedure (accurate needle route and positioning) and the intervention may involve traversing important organs such as the lung and esophagus. Meticulous preoperative evaluation is essential for DTPE. During DTPE procedure, combined fluoroscopy and CT guidance are needed for successful embolization of endoleak sac and prevention of organ or vascular injury. In addition, it is practical to use metallic guiding puncture needle. Although 21G Chiba needle is the favorable needle for DTPE, this “non-traumatic” needle is too soft to navigate precisely into the target. A 18G needle co-axis with 21G Chiba is a recommended combination for this procedure. Another key point of DTPE is the choice of embolization material. Coil and liquid embolic are two commonly used embolization materials with evidences [7-14]. A combination of Ethiodol and n-butyl-2-cyanoacrylate (NCBA) is the most widely used liquid embolization agent. In our case series, metallic coils and/or Onyx were used for endoleak embolizat ion. The major advantages of Onyx compared to glue are its non-adherence, progressive s o l i d i f i c a t i o n , c o h e s i v e n e s s , h i g h v a s c u l a r penetration and a very weak inflammatory effect on the endothelium. This allows slow and deliberate delivery without concern for injury to the target lesion upon catheter removal. Precise delivery also minimizes the possibility of misapplication or distal embolization. Onyx has been widely used for the embolization of arteriovenous malformations in the brain and has been also selected to embolize the peri-graft sac and flow channel due to several unique charac ter is t ics tha t fac i l i ta te prec ise delivery. It was reported that type 1 endoleak [15,16] in some specific situations and particularly type 2 endoleak [17-19] after stent graft treatment of abdominal aortic aneurysms were good indication for Onyx embolization. The technique of endoleak embolization is similar to that of the treatment for
Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repair澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal80brain arteriovenous malformations and thus guided by the principle of complete seal and elimination of the nidus (leak channel). The main complications and concerns of DTPE are access-related complications. The route for direct puncture using a needle should be carefully evaluated before procedure to avoid organ or vascular injury. Some published evidence indicated that direct trans-lumbar endoleak embolization provides stable and safe result for endoleak repair after EVAR. [20] Unlike abdominal aorta, upper thoracic aorta is adjacent to esophagus. Since it is easy to injure the esophagus and may cause severe consequences like infection or aorta-esophagus fistula, esophageal injury should therefore be avoided during DTPE procedure. One case report published in 2007 by Riesenman et. al. described a patient with an aorto-esophageal fistula and endograft infection developed after undergoing DTPE. [7] Endoleak located at the aortic arch possibly need parasternal route for DTPE, and pulmonary parenchyma and intercostal artery injury may be encountered. The needle injury of lung may induce pneumothorax and bleeding complications identical to that induced by CT guided lung nodule biopsy. These pneumothorax and lung parenchyma bleeds are mostly self-limited. Potential risk of spinal cord ischemia is another concern especially for type 1 endoleak repair using liquid embolization material. L i m i t a t i o n s o f o u r s t u d y i n c l u d e t h e retrospective nature and small sample size (n=3) of the study. Our study focuses on the feasibility, efficacy, and safety of DTPE for repair of endoleaks after TEVAR when conventional methods fail. Based on the literature review, despite the limitation of number reported cases, our study currently has the largest sample size among all studies on the use of DTPE for endoleak repair after TEVAR.5. ConclusionsWe concluded that DTPE can be a “bail-out” method in patients who have failed attempts at conventional repair of type 1 endoleak and persistent type 2 endoleak with aneurysm sac expansion.6. References[1] Mokashi SA, Svensson LG. Guidelines for the management of thoracic aortic disease in 2017. Gen Thorac Card iovasc Surg . 2019;67(1):59-652. DOI: 10.1007/s11748-017-0831-8[2] Leurs LJ, Harris PL, Buth J. Secondary interventions after elective endovascular r epa i r o f degene ra t ive t ho rac i c ao r t i c a n e u r y s m s : r e s u l t s o f t h e E u r o p e a n collaborators registry (EUROSTAR). J Vasc Interv Radiol 2007;18:491-5. DOI: 10.1016/j.jvir.2007.01.018[3] Morales JP, Greenberg RK, Lu Q, et al . Endoleak following endovascular repair of thoracic aortic aneurysm: etiology and outcomes. J Endovasc Ther 2008;15:631-8. DOI: 10.1583/08-2551.1[4] Pa te l HJ , Wi l l i ams DM, Drews JD, e t a l . A 20-year exper ience wi th thoracic endovascu la r ao r t i c r epa i r. Ann Surg . 2014;260:691-696; discussion 696-697. DOI: 10.1097/SLA.0000000000000930[5] Parmer SS, Carpenter JP, Stavropoulos SW, et al. Endoleak after endovascular repair of thoracic aortic aneurysms. J Vasc Surg. 2006;44(3):447-52. DOI: 10.1016/j.jvs.2006.05.041[6] Preventza O, Wheatley GH 3rd, Ramaiah V G , e t a l . M a n a g e m e n t o f e n d o l e a k associated with endovascular treatment of descending thoracic aortic diseases. J Vasc Surg. 2008;48(1):69-73. DOI: 10.1016/j.jvs.2008.02.032[7] Riesenman PJ, Farber MA, Mauro MA, et al. Aortoesophageal fistula after thoracic endovascular aortic repair and transthoracic embolization. J Vasc Surg. 2007;46(4):789-91. DOI: 10.1016/j.jvs.2007.05.036[8] Stavropoulos SW, Tucker J, Carpenter JP. Thoracic endoleak embolization using a direct percutaneous puncture of the endoleak
Direct transcutaneous puncture embolization of endoleak after thoracic endovascular aortic repair第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 81through lung parenchyma. J Vasc Interv Radiol. 2009;20(9):1248-51. DOI: 10.1016/j.jvir.2009.05.032[9] Klein S, Picus D. Thoracic type II endoleak embolization using direct percutaneous puncture. Cardiovasc Intervent Radiol. 2012;35(5):1249-52. DOI: 10.1007/s00270-011-0283-y[10] Mussa FF, Maldonado TS, Schwartz CF. P e r c u t a n e o u s e m b o l i z a t i o n o f p a t e n t i n t e r c o s t a l a r t e r y c a u s i n g p e r s i s t e n t t ype I I endo leak and sac en l a rgemen t of thoracoabdominal aneurysm 2 years after hybrid repair. J Thorac Cardiovasc Surg. 2012;144(4):e102-6. DOI: 10.1016/j.jtcvs.2012.06.056[11] Katada Y, Kondo S, Takahashi S, et al. Direct percutaneous puncture embol iza t ion of type II endoleak using a coaxial technique. J Endovasc Ther. 2013;20(1):34-8. DOI: 10.1583/12-4065.1[12] Kreusch AS, Samuels S, Benenati JF, et al .Direct percutaneous sac injection for treatment of a thoracic type II endoleak. J Vasc Interv Radiol. 2013;24(7):1071-3. DOI: 10.1016/j.jvir.2013.03.024[13] B a n g a r d C , F r a n k e M , P f i s t e r R , e t a l . T h o r a c i c t y p e I a e n d o l e a k : d i r e c t percutaneous coil embolization of the aortic arch at the blood entry site after TEVAR and double-chimney stent-grafts. Eur Radiol. 2014;24(6):1430-4. DOI: 10.1007/s00330-014-3143-8[14] Katada Y, Kondo S, Tsuboi E, et al. Type IA endoleak embolization after TEVAR via direct transthoracic puncture. Jpn J Radiol. 2015;33(3):169-72. DOI: 10.1007/s11604-015-0392-7[15] Grisafi JL, Boiteau G, Detschelt E, et al. Endoluminal treatment of type IA endoleak with Onyx. J Vasc Surg 2010;52:1346-9. DOI: 10.1016/j.jvs.2010.06.021[16] Hen r ik son O , Roos H , Fa lkenbe rg M. Ethylene vinyl alcohol copolymer (Onyx) to seal type 1 endoleak. A new technique. Vascular 2011;19:77-81. DOI: 10.1258/vasc.2010.oa0257[17] Nevala T, Biancari F, Manninen H, et al. Type II endoleak after endovascular repair of abdominal aortic aneurysm: effectiveness of embolization. Cardiovasc Intervent Radiol 2009;33:278-84. DOI: 10.1007/s00270-009-9685-5[18] Abularrage CJ, Patel VI, Conrad MF, et al. Improved results using Onyx glue for the treatment of persistent type 2 endoleak a f t e r endovascu la r aneurysm repa i r. J Vasc Surg 2012;56:630-6. DOI: 10.1016/j.jvs.2012.02.038[19] Mass is K, Carson WG, Rozas A, e t a l . Treatment of type II endoleak with ethylene-v iny l -a lcohol copolymer (Onyx) . Vasc Endovascular Surg 2012;46:251-7. DOI: 10.1177/1538574412442401[20] Baum RA, Carpenter JP, Golden MA, et a l . Trea tment of type 2 endoleak af te r endovascular repair of abdominal aortic aneurysms: comparison of t ransar ter ia l a n d t r a n s l u m b a r t e c h n i q u e s . J Va s c S u rg . 2 0 0 2 ; 3 5 : 2 3 – 2 9 . D O I : 1 0 . 1 0 6 7 /mva.2002.121068
Yi LIN et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal82A case report of pulmonary epithelioid hemangioendotheliomaYi LIN1*, Thazin HLAING2, Chi Leong LAM1, Sio In WONG2, AbstractSummary: Pulmonary epithelioid hemangioendothelioma (EHE) is a rare neoplasm with variable clinical behaviour. It can manifest as multiple pulmonary nodules, pulmonary reticulonodular opacities, or diffuse infiltrative pleural thickening. Currently, there are no approved systemic agents specifically for EHE, and treatment selection remains uncertain. We present a case of a female patient with EHE who initially presented with lung lesions and pleural effusion, later found to have intrahepatic lesions. Molecular assay confirmed the presence of the WWTR1-CAMTA1 fusion gene, highly specific for EHE. The patient was treated with a regimen consisting of the immune checkpoint inhibitor Pembrolizumab and the anti-angiogenesis tyrosine kinase inhibitor Axitinib. Her dyspnea improved during the course of treatment. The response to this regimen will be assessed using follow-up imaging. It is important to identify patients with EHE harbouring specific fusion genes for treatment response analysis. Further studies are needed due to the rarity of EHE, and uncontrolled trials may be inevitable.. Keywords: Epithelioid hemangioendothelioma; Immune checkpoint inhibitor; Anti-angiogenesis TKI(tyrosine kinase inhibitor) 1Department of oncology, Conde de São Januário General hospital, Macao2Department of anatomical pathology, Conde de São Januário General hospital, Macao*Correspondence to: Yi Lin, galaxyly2010@hotmail.com1. IntroductionEHE i s a ma l ignan t vascu la r neop lasm, f e a t u r i n g a n e p i t h e l i o i d e n d o t h e l i a l c e l l population in a distinctive myxohyaline stroma. These fea tu res can , however, be a l so found in p r imary adenoca rc inoma , meso the l i oma , and large-cell lymphoma. Corrin et al . , using immunohistochemical techniques, demonstrated the presence of malignant cells deriving from a lineage capable of differentiation along endothelial lines. EHE has an incidence of 0.038/100,000 per year and prevalence <100,000, showing a predominance in women. The incidence peaks in the fourth to fifth decade [1]. 2. Case presentationA 44-year-old female, non-smoker, presented with right chest discomfort to another hospital in December 2022. Chest CT scan showed the following findings: a nodule 1.7x1.2 cm in the apical posterior segment of r ight upper lobe, moderate amount of pleural effusion on the right side, multiple right pleural nodules among which the biggest one measured up to 0.6cm, and bilateral pulmonary tiny nodules (0.2~0.5cm), without any enlarged pulmonary hilar or mediastinal lymph nodes. The right upper lung nodule was biopsied. The pathology was described as small nests of epithelioid tumor cells within the expanded alveoli spaces and septa, which displayed eosinophilic c y t o p l a s m a n d o v a l b l a n d - l o o k i n g n u c l e i . Occas ional cytoplasmic vacuoles were seen.
A case report of pulmonary epithelioid hemangioendothelioma第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 83IHC profile of tumor cells was as follows: EMA (partial +), TTF1 (-), CK (weakly +), CAM5.2(-), CK7(partially +), Napsin A (-), ER (-), PR (-), SPA (-), Ki67(partial hot zone 20%+), Vimentin (+++), CD34(+++), ERG(+++), CD31(+++) [Figure 1]. The overall features are compatible with the diagnosis of EHE. WWTR1 plus TFE3 break-apart FISH tests in our hospital yielded a positive result, substantiating the above-mentioned diagnosis. She received axitinib 5mg q12h combined with pembrolizumab 200mg on day 1 every 3 weeks in HK from Jan 20th 2023. Her dyspnea ameliorated. This regimen was continued in our hospital between early April and mid-June 2023 for 4 cycles. Further imaging study will be undertaken for response assessment. (a) HE (b) Vimentin(c) CD34 (d) ERG Figure 1. Histopathologic findings of hemangioendothelioma: (a) Higher magnification of the tumor reveals vacuolation of some of the tumor cells, representing primitive angiogenesis. (b) Immunostaining for Vimentin revealed positivity of the neoplastic cells (brown colour), confirming the mesenchymal origin of tumor cells (c) Immunostaining for CD34 revealed positivity of the neoplastic cells (brown colour), confirming the endothelial lineage of the tumor. (d) Immunostaining for ERG revealed positivity of the neoplastic cells (brown colour), further confirming the endothelial lineage of the tumor.
A case report of pulmonary epithelioid hemangioendothelioma澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal843. DiscussionEHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma. As for the high-grade one, it is marked by a high propensity for systemic involvement. It can arise anywhere in the body and have various presentations. Lau et al. [1] found that the most commonly affected organs were liver and lung. Pulmonary EHE may cause dyspnea, cough, hemoptysis, and clubbing, whereas many patients are asymptomatic at presentation and manifest often with an incidental finding on imaging studies. Radiographically, bilateral multiple nodular nodules are the most common presentation [2]. The prognosis is very variable, with survival ranging from less than one year up to 30 years. The only validated prognostic factors are the extent of disease at presentation and the presence of systemic signs. In patients with serosal involvement with/without effusion, the expected survival ranges from 1 to 11 months [3].Immunohistochemically, EHE consistently expresses endothelial differentiation markers such as CD31, ERG, CD34 and FLI-1. Molecularly, up to 90% cases harbor a t (1;3) (p36.3;q25) translocation, leading to the formation of WWTR1-CAMTA1 fusion gene, whereas a smaller subset shows an alternative genetic aberration represented by a t(X;11)(p11;q22) translocation, leading to a YAP1-TFE3 fusion [4]. WWTR1 and YAP both exert a pro-oncogenic transcriptional function. EHE is typically refractory to the antitumor d r u g s u s e d i n s a r c o m a s . F o r p a t i e n t s w i t h asymptomatic metastatic disease, active surveillance is the upfront preferred approach. Patients with serosal effusion and/or marked systemic symptoms tend to have a rapidly progressive course, therefore in our case, an early start of systemic therapy was mandated.Chemotherapy Data are conflicting for the efficacy. As for VEGFR inhibitors: Bevacizumab and sorafenib have also demonstrated modest clinical efficacy in phase II trials, with objective responses ranging from 13 to 29 percent. In one observational study of 10 patients with progressive EHE treated with pazopanib, objective responses were seen in two patients (20 percent). Median progression-free survival (PFS) and overall survival were approximately 26 months [5].Immune checkpoint inhibitors combined with antiangiogenic TKI regimens has gotten approval for several hypervascular malignancies, such as advanced hepatocellular and renal cell carcinoma regardless of PD-L1 status. The ASPL-TFE3 fusion is universally present in alveolar soft part sarcoma (ASPS) and leads to upregulation of proangiogenic factors. This was the rationale behind a phase II study of pembrolizumab with axitinib for patients with advanced sarcomas including epithelioid sarcoma. The combination of pembrolizumab and axitinib mediated objective responses in 6 (55%) of 11 ASPS, and 1 of 1 epithelioid sarcoma [6]. A similar regimen that is under investigation (ClinicalTrials.gov Identifier: NCT04784247)”, set “vascular sarcoma” as a treatment arm with cases having EHE included. 4. Conclusion Given the rar i ty of EHE, i t i s inevi table that uncontrolled studies data were included. The main chal lenge for uncontrol led s tudies is the unpredictable behaviour of EHE. Global c o l l a b o r a t i o n i n c l u d i n g e v e n c a s e r e p o r t s , particularly those having WWTR1-CAMTA1 and YAP1-TFE3 fusions will be helpful to advance our knowledge concerning EHE. 5. References[1] Lau K, Massad M, Pollak C, et al. Clinical p a t t e r n s a n d o u t c o m e i n e p i t h e l i o i d hemangioendo the l ioma wi th o r wi thou t pulmonary involvement: insights from an internet registry in the study of a rare cancer. Chest 2011, 140:1312-1318. doi: 10.1378/
A case report of pulmonary epithelioid hemangioendothelioma第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 85chest.11-0039.[2] K. Liu, P. Xie, W. Peng, et al. The computed tomographic findings of pulmonary epithelioid hemangioendothelioma, Radiologia Medica 2014, 119: 705–713. doi: 10.1007/s11547-013-0376-6.[3] Woo JH, Kim TJ, Lee KS. et al. Epithelioid h e m a n g i o e n d o t h e l i o m a i n t h e t h o r a x : clinicopathologic, CT, PET, and prognostic features. Medicine (Baltimore). 2016;95: e4348. doi: 10.1097/MD.0000000000004348.[4] E r r a n i C , Z h a n g L , S u n g Y S , e t a l . A novel WWTR1-CAMTA1 gene fus ion i s a cons i s t en t abnormal i ty in ep i the l io id hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer 2011;50: 644-653. doi: 10.1002/gcc.20886.[5] F r ezza AM, Rav i V, Lo Vu l lo S , e t a l . Systemic therapies in advanced epithelioid haemangioendothel ioma: A retrospect ive international case series from the World Sarcoma Network and a review of literature. Cancer Med 2021 Apr;10:2645-2659. doi: 10.1002/cam4.3807. [6] Wilky BA, Trucco MM, Subhawong TK, et al. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. The Lancet Oncology 2019;20:837–48. doi: 10.1016/S1470-2045(19)30153-6.
����澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal86外傷性頸內動脈海綿竇瘺 1 例報道施偉達*，譚文斌，鍾景生，梁溢貞，江瑞洲摘 要澳門是一個以電單車為主要交通工具的小城，電單車相關的交通意外時有發生。根據澳門統計暨普查局最新資料，涉及電單車而受傷的交通意外平均每年約4000宗 [1]。以下，我們報導一例因電單車交通意外導致顱底骨折並遲發性外傷性頸動脈-海綿竇瘺（Traumatic carotid-cavernous sinus fistula, TCCF）。 TCCF是一種少見的特殊疾病，因外傷引起頸動脈海綿竇段動脈壁或其分支破裂，導致與海綿竇之間形成異常動靜脈交通。臨床上，TCCF患者常因眼球突出、結膜水腫、充血、視力減退等症狀到眼科就診[2]。如果對該病認識不足，可能導致誤診而延誤治療，因此本病例對TCCF的臨床症狀、影像學表現、介入診斷及治療、治療效果進行分析總結。關鍵詞：外傷性頸動脈海綿竇瘺；顱底骨折；CT；MRI；影像學診斷；介入治療；栓塞AbstractMacau is a small city where motorcycles are the main means of transportation, and traffic accidents related to motorcycles occur frequently. According to the latest data from the Governo da Região Administrativa Especial de Macau Direcção dos Serviços de Estatística e Censos DSEC, the average number of traffic accidents involving motorcycle injuries is about 4,000 per year [1]. We here report a case of skull base fracture with delayed traumatic carotid-cavernous sinus fistula (TCCF) caused by a motorcycle traffic accident. TCCF is a rare and special disease. It causes traumatic rupture in the arterial wall of the carotid-cavernous sinus segment of internal carotid artery or its branches, resulting in abnormal arteriovenous communication with the cavernous sinus. TCCF patients often present to the ophthalmology department for symptoms like exophthalmos, conjunctival edema, hyperemia, and vision loss [2]. Ophthalmologists, radiologists and other clinicians must be aware of such possibilities when a history of skull base trauma has been elicited. This case report analyzes and summarizes the clinical symptoms, imaging manifestations, interventional diagnosis and treatment as well as therapeutic effect of TCCF.Keywords: Traumatic carotid-cavernous fistula; skull base fracture; CT; MRI; imaging diagnosis; interventional treatment; embolization仁伯��合����科*��作者：���,swinghorn@yahoo.com.hk1. 簡介頸動脈 -海綿竇瘺（CCF) 是頸動脈主幹或分支與海綿竇之間異常溝通，形成頸內動脈或頸外動脈 (ICA、ECA) 到海綿竇 (CS) 的動靜脈 (A-V) 分流，導致海綿竇內壓力增高，引流靜脈擴張 [4]，[5]， [6]。頸內動脈 ICA與海綿竇 (CS) 之間直接溝通而形成高流速的瘺管約占 CCF 的 75%，並且最常見繼發於外傷後 (70%-90%) [5]，[6]，[7]，[8]。外傷性顱底骨折常合併頸動脈 -海綿竇瘺 (TCCF)，約 3.8% 的顱底骨折患者存在 TCCF[3]。動靜脈分流可能會破壞腦或眼靜脈回流路徑，導致靜脈充血，繼發性腦出血，或眼部症狀惡化等。 因此，臨床上頸動脈海綿竇瘺常見症狀為搏動性眼
�傷性頸內動����� 1例��澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal88圖 1 急診創傷 CT見左上頜竇、左蝶竇、左眼眶外側壁、左蝶骨翼、左顴弓、左顳骨多處骨折。圖 2 術前患者左眼瞼腫脹、結膜充血水腫，左眼眶上緣裂傷縫合後。圖 3 CTA 左側頸內動脈海綿竇段，病灶周圍海綿竇造影劑顯影圖 4 CTA血管重建顯示左側頸內動脈海綿竇段迂曲伴海綿竇顯影
�傷性頸內動����� 1例��第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 89圖 5 診斷性 DSA 動態顯示左側頸內動脈海綿竇段有大量造影劑滲入海綿竇，同時伴有病灶外周靜脈血管明顯擴張。圖 6 正側位腦血管 DSA造影顯示：經 GDC�充瘺口後造影示，瘺口已完全填充覆蓋，原靜脈血管團顯影消失。5. 參考文獻[1] 澳門統計暨普查局 2 0 2 2時間序列資料庫https:/ /www.dsec.gov.mo/ts/#!/step2/Latest5Indicator/zh-MO/64187[2] Liang J, Xie X, Sun Y, et al . Bilateral carotid cavernous fistula after trauma: a case report and literature review. Chin Neurosurg J. 2021;7:46.[3] Yang XF, Wen L, Shen F, Li G, Lou R, Liu WG, Zhan RY. Surgical complications secondary to decompressive craniectomy in patients with a head injury: a series of 108 consecutive cases. Acta Neurochir (Wien). 2008 Dec;150(12) :1241-7 ; d i scuss ion 1248. Epub 2008 Nov 13. PubMed PMID: 19005615[4] BA Moralis, VN Yamaki, JGMP Caldas, SW Paiva, H Matushita, MJ Teixeira. Post-traumatic carotid-cavernous fistula in a
�傷性頸內動����� 1例��澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal90pediatric patient: a case-based literature review Childs Nerv Syst, 34 (2018), pp. 577-580[5] J A E l l i s , H G o l d s t e i n , E S C o n n o l y, PM Meyers. Carotid-cavernous fistulas Neurosurg Focus, 32 (5) (2012), p. E9[6] B M i l l m a n , N A G i d d i n g s . Tr a u m a t i c carotid-cavernous sinus fistula with delayed epistaxis Ear Nose Throat J, 73 (6) (1994), pp. 408-411[7] G Debrun, F Vińuela, A Fox, K Davis, HS Ahn. Indications for treatment and classification of 132 carotid-cavernous fistulas. Neurosurgery, 22 (2) (1988), pp. 285-289[8] Chaudry, SM Elkhamry, W Al-Rashed, TM Bosley. Carotid cavernous f is tula: ophthalmological implications. Middle East Afr J Ophthalmol., 16 (2) (2009), pp. 57-63[9] AD Hende r son , NR. Mi l l e r. Ca ro t id -cavernous f is tula : current concepts in aetiology, investigation, and management. Eye, 32 (2018), pp. 164-172[10] Pülhorn H, Chandran A, Nahser H, et al. Case report: traumatic carotid-cavernous fistula. J Trauma Nurs. 2016;23:42–4.[11] Hamedani H, Hellmann D, Boyce W, et al. Traumatic carotid-cavernous fistula: a case report. Radiol Case Rep. 2022;17:1955–8.[12] Iancu D, Lum C, Ahmed ME, et al. Flow d ive r s ion in the t r ea tmen t o f ca ro t id injury and carotid-cavernous fistula after transsphenoidal surgery. Interv Neuroradiol. 2015;21:346–50.[13] Wendl CM, Henkes H, Martinez Moreno R, et al. Direct carotid cavernous sinus fistulae: vessel reconstruction using flow-diverting implants. Clin Neuroradiol. 2017;27:493–501.[14] Ting W, Richard SA, Changwei Z, et al. Concomitant occurrence of clinoid and cavernous segment aneurysms complicated with carotid cavernous fistula: a case report. Medicine (Baltim). 2019;98:e18184.[15] Nakae R, Nagaishi M, Takano I , et al . Transvenous coi l embolizat ion for the treatment of carotid cavernous fistula after pipeline placement: a case report. J Stroke Cerebrovasc Dis. 2018;27:e65–9.[16] Chaudhry IA, Elkhamry SM, Al-Rashed W, e t a l . C a r o t i d c a v e r n o u s f i s t u l a : ophthalmological implications. Middle East Afr J Ophthalmol. 2009;16:57–63.[17] Ding CL, Zhang CL, Hua F, Xi SD, Zhou QW, Wang HJ, Chen JJ, Qiu J. Traumatic carotid-cavernous fistula with perimedullary venous drainage and delayed myelopathy: A case report. Med Int (Lond). 2021 Sep 17;1(5):16. doi: 10.3892/mi.2021.16.
Wai I CHOI et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 91A case of button battery in the esophagus in childrenWai I CHOI*, Chi Shing KWOK AbstractEsophageal foreign body is one of the common causes of children emergencies. Diagnosis of esophageal foreign body in children is often delayed due to the lack of description of medical history, resulting serious consequences. This is a case of a little girl who attended emergency department because of difficulty in swallowing for one day and fever for 4 hours. Chest X-ray confirmed that there was a round high-density shadow in the 5th to 7th cervical vertebra, diagnosed as esophageal foreign body. She was arranged emergency surgery. At operation, a battery button in the first stenosis area of the esophagus was removed, and her esophageal mucosa was found to be corroded with chemical burns. Postoperatively, she was inserted an NGT for feeding and was given anti-infective and Nonsteroidal Anti-inflammatory medicine. MRI examination before extubation of NGT Showed irregular abnormal shadows on both sides of the upper esophageal segment, considered to be delayed esophageal perforation, but no infections were noted in the esophageal space. With prolongation of treatment time to promote the repair of perforation, the girl was able to eat normally after one month without dysphagia. She was subsequently followed up for 2 years, and was found to have recovered well with no sequelae. This case suggests that it is necessary to strengthen the health education of parents, so as to protect or prevent children from contacting items that are easy to swallow. Clinicians should also need to be vigilant in order to detect esophageal foreign early and treat immediately. Button battery foreign bodies in the esophagus, in addition to causing mechanical obstruction, may result in chemical corrosion injury which is an important cause of complications. Therefore, sufficient time is needed for treatment of such foreign bodies to reduce possible complications.Keywords: children; foreign body of the esophagus; A button batteryDepartment of Otorhinolaryngology Head and Neck Surgery, Kiang Wu Hospital, Macau.*Correspondence to: Wai I CHOI, mo_choi@hotmail.com1. IntroductionEsophagea l fo r e ign body i s common in children. Although most have a good prognosis, coin cell battery foreign bodies lodged in the esophagus of children are extremely dangerous and can lead to choking and other hazards. Recently, there has been a gradual increase in the number of accidents involving button batteries in children. As the resultant chemical burns can cause more serious complications, clinicians should be vigilant to look out for possible occurrence of such esophageal foreign bodies. In April 2020, our department had admitted one case of a button battery foreign body lodged in the esophagus of a young girl, which is reported as follows.2. Clinical informationA female child aged 2 years and 5 months was admitted to our hospital on 2020-04-08. She complained of difficulty in swallowing and refusal to eat for one day with fever for 4 hours and was sent to the emergency room in KWH. When seen,
A case of button battery in the esophagus in children澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal92the child had drooling, vomiting and salivation, and was suspected to have swallowed a foreign body at night while playing on her own. Physical examination showed temperature of 38.3 ℃ , no congest ion or swel l ing of the pharyngeal mucosa, no swelling or obvious pressure pain in the neck. Routine blood examination revealed WBC 22.06X109 /L, NEU 0.848%. Chest X-ray confirmed a round-sharp high-density shadow at the level of the cervical level 5-7 vertebrae, which was diagnosed as a foreign body in the esophagus [Figure 1]. After admission, emergency surgery was performed under general anesthesia. Esophagoscope exploration was carried out and a foreign body was removed from the entrance of the esophagus, 10 cm from the upper incisor . A button battery (size 2cm×2cm) and several pieces of brown and black paper-like foreign body were found[Figure 2]. The battery metal layer has been etched and the mucosal surface of the esophagus revealed scattered brown-black scab blocks suggestive of chemical burn. The affected area was carefully and gently scrubbed with saline cotton pad, after which the mucosa was seen to be porcelain white and did not reveal any obvious perforation. Intraoperatively, a nasogastric tube (NGT) was placed. Postoperatively, the pa t ien t was g iven empir ica l medica t ion , including clafron + flagyl anti-infective treatment for 8 days, and dexamethasone anti-inflammatory therapy for 5 days. The patient’s fever subsided on the postoperative day 2, and her routine blood examination revealed: WBC 9.66X109/L, NEU 0.557. To be cautious, the patient was kept on for enteral nutrition through the NGT, with good weight gain at discharge (10.3 kg weight gain to 11.9 kg). The patient had no tenderness nor swelling in the neck in the post-operative period. Although the patient recovered well after surgery, since the chemical burn of the esophagus was obvious at esophagoscopy, MRI scan of the neck was performedbefore extubation of NGT. The scan showed irregular abnormal shadow, which was considered to be possible gas, on both sides of the upper esophageal segment of the cervical level 4-7 vertebral body, both at the pyriform recess and upper esophagus. Although the child’s clinical symptoms were not obvious, the diagnosis was considered to be delayed upper esophageal perforation due to chemical burns, without associated infections in the esophageal space (Figure 3). The parents requested that the child be transferred to another hospital for treatment. The child subsequently continued to receive conservative treatment. She was started on a full-fluid transoral diet, and her NGT was removed at 4 weeks postoperatively and returned to solid diet after another week. The MRI scan of her neck showed no special condition. When followed up in 2 years’ time, no esophageal stricture was detected on imaging. The patient had no swallowing discomfort and was growing well.3. DiscussionForeign body in the esophagus is one of the common emergencies in pediatric otolaryngology, mostly seen in children between the ages of 6 months and 6 years[1]. Button batteries are often found in toys and small appliances, and children have a habit of holding objects in their mouths while playing. As a result, there has been a gradual increase in the number of accidents involving foreign bodies in the esophagus f rom but ton batteries in children[2, 3] . Data show a 6.7-fold increase in button battery ingestion incidents between 1985 and 2009.[4]T h e r i s k o f e s o p h a g e a l f o r e i g n b o d y complications is related to the type of foreign body. Coin-type foreign bodies have the lowest complication rate of all types of foreign bodies[6], but may cause airway obstruction and asphyxia. Bar/sharp foreign bodies have a higher risk and are prone to complications such as perforation and bleeding[7]. Button batteries have a high chance of complications. In addition to the mechanical blockage, they may cause esophageal perforation, t r acheoesophagea l f i s tu la , hemor rhage , and esophageal s tr icture[8] . The main injuries or
A case of button battery in the esophagus in children第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 93complications caused by button batteries lodged in the esophagus are: (1) Chemical injury: The electrolyte inside the button battery is usually sodium hydroxide or potassium hydroxide. After the battery is embedded in the esophagus, the metal layer on the surface of the battery can be etched and leaked. The leaking electrolyte will corrode the esophageal mucosa, causing liquefied necrosis of the mucosa[9]. (2) Electrical burns: The esophagus is a humid environment, which can cause short-circuit with the button battery. The leakage of electricity generates heat, causing mucosal burns[10]. (3) Mechanical injury: Local mechanical compression can cause tissue necrosis. (4) Toxic injury: Local absorption of heavy metals from the battery in the esophageal mucosa can cause toxic reaction. Button batteries can cause burns damage to the esophageal mucosa within 1 hour. If more than 4 hours, it can lead to serious necrosis of the esophageal mucosa tissue[11] . Characteristics of button battery esophageal foreign bodies in children include: (1) The incidents most ly occur in ear ly chi ldhood due to their curiosity, active behavior, insufficient cognitive ability and self-protection awareness. (2) It is not easy to obtain a history of ingestion of the foreign body in young children. This can easily cause delay in treatment, resulting in complications due to the prolonged embedment of button batteries in the esophagus. (3) Diagnosis of esophageal foreign body in children is difficult as some children are asymptomatic[5]. The most common symptoms in children are dysphagia and vomiting, or crying and salivation. (4) Button batteries can show distinctive double density finger ring-like changes on X-ray [Figure 1], whereas coin-like foreign bodies do not have this double ring symptom.Esophageal perforation is one of the common complications of esophageal foreign body in young children. Some perforations are caused by sharp foreign bodies puncturing the tube wall, or foreign bodies pressing the tube wall resulting in ischemic necrosis, or foreign bodies releasing chemical substances resulting in inflammation and corrosion of the tube wall. Button battery releases chemicals which gradually penetrate deep into the tissue and are not conducive to tissue repair. There are also multiple factors which can cause delayed perforation with button battery. In this case, although the foreign body was removed, the chemical substances that penetrated into the tissue were still corroding, resulting in delayed perforation. Therefore, we believe that the perforation in this case is not completely caused by local infection, but is mainly caused by chemical penetration. Due to the lack of retrospective analysis of large numbers of cases, there is no consensus on the factors associated with complications of intra-esophageal button battery foreign bodies. However, this article postulates that the risk factors for complications in this particular case are related to the amount of e lectr ic i ty contained in the battery, the time of retention, and the location. For clinicians to make a correct diagnosis for patients with such foreign bodies, they should take a detailed medical history and pay attention to the "double ring sign" features in the X-ray, CT or MRI scans to help diagnose the cause quickly. In children with ingested button battery lodged in the esophagus, the battery must be removed as soon as possible, regardless of the length of time it has been embedded and the age of the child. The chemical residues should be carefully and gently removed with saline cotton pads during surgery. A NGT must be left in place after surgery and the child should be monitored for possible tracheoesophageal fistula and other complications. Such patients should be followed up regularly to pay close attention to the occurrence of esophageal strictures or other long-term complications. Family and education center should be advised and urged to raise the awareness of parents and teachers of the dangers of button batteries and to prevent children from accidentally swallowing them.
A case of button battery in the esophagus in children澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal94Figure 1. Figure 2.Figure 1.X-ray , "double ring sign" Figure 2.Foreign body in the esophagus (button battery, piece of paper)Figure 3. Figure 3. MRI of the neck with free gas nearby esophagus(white arrow indicates free gas para-esophageal free gas)4. References[1] S u g a w a C , O n o H , Ta l e b M , e t a 1 . Endoscopic management of foreign bodies in the upper gastrointestinal tract: A review. World J Gas t ro in tes tEndosc . 2014, 6f 10):475-481.[2] LEE J H, LEE J H, SHIM J O, e t a l . Foreign body ingestion in children: should button batteries in the stomach be urgently removed [J]. Pediatr Gastroenterol Hepatol Nutr, 2016, 19(1): 20-28.[3] Raboei EH, Syed SS, Maghrabi M, et al. Management of button battery stricture in 22-day-old neonate [J]. Eur J PediatrSurg, 2009, 19(2):130-131.[4] Litovitz T, Whitaker N, Clark L, et al . Emerging battery-ingestion hazard: clinical implications[ J]. Pediatrics, 2010, 125(6): 1168-1177.
A case of button battery in the esophagus in children第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 95[5] Bolton SM, Saker M, Bass LM. Button ba t t e ry and magne t inges t ions in the pediatric patient[ J]. CurrOpinPediatr, 2018, 30(5 ): 653-659.[6] Ren Lu, Geng Lan Lan, Xiao Wei Qiang, et al. A case series report of 1,257 cases of gastrointestinal foreign bodies in children: the Chinese Journal of Evidence-Based Pediatrics [J] Vol. 12, No. 5, October 2017.[7] Panda NK, Sastry KV, Panda NB, et a1. Management of sharp esophageal foreign bodies in young chi ldren: a cause for worry. International Journal of Pediatric Otorhinolaryngology, 2002, 64(3): 243-246.[8] Kramer RE, Lemer DG, L in T, e t a1 . Management of Ingested Foreign Bodies in Chi ld ren : a Cl in ica l Repor t o f the N A S P G H A N E n d o s c o p y C o m m i t t e e . j P e d i a t r G a s t r o e n t e r o l N u t r , 2 0 1 5 , 60(4):562-574.[9] Eliason MJ, Ricca RL, Gal lagher TQ. Bu t ton ba t t e ry inges t ion in ch i ld ren . CurrOpinOtolaryngol Head Neck Surg, 2017, 25 (6): 520-526.[10] Litovitz T, Whitaker N, Clark L. Preventing battery ingestions: an analysis of 8648 cases. Pediatrics, 2010, 125(6):1178-1183.[11] Kim KK，Kim UR，Kim JY．But ton battery impaction in nasal cavity[J]．J Korean Med Sci，1999，14(2)：210．[12] Wang J, Luo RZ, Zhou LF, et al. Injury and mechanism of esophageal foreign body button battery on rabbit esophagus. Modern Preventive Medicine, 2012, (13): 3322-3325.
Si Man LEONG et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal96Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapySi Man LEONG*, Io Hong CHOUAbstractBronchopulmonary sequestration (BPS) may cause prenatal pleural effusion (PE) or even hydrops. We report a case of fetal left bronchopulmonary sequestration diagnosed at gestational age (GA) of 22 weeks in Conde de Sao Januario General Hospital, Macau. Regular monitoring of the fetus by ultrasonography (USG) showed persistent pleural effusion that worsened progressively. The pleural effusion of the fetus had decreased only slightly when given steroid treatment in hospital. Thus, we held a multidisciplinary team meeting, with members including Obstetrics, Pediatrics and Cardiothoracic and Pulmonary Surgery, to discuss the treatment plan. The final decision was to perform intrauterine thoracentesis to treat the fetal pleural effusion [1]. Fetal intrauterine thoracentesis was subsequently done with complete regression of PE and without post-procedural complications. The fetal condition remained well after delivery.Keywords: Bronchopulmonary sequestration; Pleural effusion; Congenital pulmonary airway malformation volume ratio; Intrauterine thoracentesis.Department of Obstetrics and Gynecology, Conde de São Januário General hospital, Macau*Correspondence to: Si Man LEONG, 3433255167@qq.com1. BackgroundBronchopulmonary sequestration (BPS) is a rare congenital lung mass. It accounts for only 0.15% to 6.4% of congenital lung malformations. BPS consists of a nonfunctioning mass of lung tissue that lacks normal communication with the tracheobronchial tree. It is classified anatomically as intralobar sequestrations (ILS) or extralobar sequestrations (ELS). BPS can affect the normal development of the fetal airways, lung parenchyma, and vasculature. Since the majority of BPS cases are diagnosed during the second trimester but will stabilize or partially regress during the third trimester, they can be managed expectantly. In the absence of other significant congenital anomalies, the short-term and long-term postnatal prognosis of BPS is usually very good [2].2. Case presentationThis pregnant mother was a 34 year-o ld female, G 1P 0, GA 30+6weeks, post IVF -ET (Day 5 embryo) on 2022/12/15 with IVF-EDC on 2023/09/02. She was found to have ‘fetal bronchopulmonary sequestration’ by USG at GA 22+ weeks and was admitted due to increasing size of the fetal bronchopulmonary sequestration with progressive pleural effusion for 1 day. She was asymptomatic without abdominal pain, vaginal bleeding or abnormal fetal movement.2.1 Prenatal care historyThe pregnant mother has A-thalassemia while her husband is normal . Nuchal Translucency (NT) done on 2023/03/01 (GA 13+4week) was within normal l imit . A Non-invasive Prenatal Testing (NIPT) done at same time showed low risk. Gestational diabetes mellitus was confirmed by OGTT and her blood glucose level was well
Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapy第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 97controlled by diet. 2.2 Past history She has hypothyroidism under control with 75mcg levothyroxine. She also has Polycystic O v a r y S y n d r o m e ( P C O S ) s i n c e 2 0 0 9 , a n d family history of hyperthyroidism. She denied a n y f a m i l i a l c o n g e n i t a l g e n e t i c d i s e a s e o r malformations.3. Invest igationsSecond trimester USG (Level I) on 2023/05/05 (GA22+6 week)L e f t l u n g h y p e r e c h o i c i m a g e a b o u t 2.51x2.24x1.72cm in size in the fetus was found. Fetal bronchopulmonary sequestration was considered, and congenital pulmonary airway malformation volume ratio (CVR) was 0.44. No fetal hydrops, cardiomegaly or pleural effusion was observed. No other malformation was noted (Figure 1).Figure 1.Figure 2.Level II USG on 2023/06/07 (GA27+4 week) A left lung lower lobe hyperechoic image of 3.29 x 3.25 x 1.87cm in size was noted in the fetus. Some free liquid was found in the thorax. The fetal heart was pushed to right side. The diagnosis of fetal BPS was considered. No fetal hydrops, cardiomegaly or other malformation was found (Figure 2).
Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapy澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal98Figure 3.Figure 4.Level II USG on 2023/06/28 (GA30+4week)The fetus was in cephalic presentation, with an estimated fetal weight (EFW) of 1869g. The left lung lower lobe hyperechoic image in the fetus was about 3.93x3.35x2.72cm in size with left pleural effusion. The CVR was 0.64. The fetal heart Level II USG on 2023/06/30 (GA30+6week)The fetus was in cephalic presentation. The left lung lower lobe hyperechoic image in the fetus was about 4.12x2.97x2.55cm in size. Moderate left pleural was pushed to right side, but no cardiomegaly or pericardial effusion was noted. The amniotic fluid volume was normal, with Amniotic Fluid Index (AFI) of 22.6cm. Ductus Venosus Doppler was normal. Fetal bronchopulmonary sequestration was considered (Figure 3).effusion was observed with CVR of 0.56. There was mild ascites around 0.74cm in depth. The AFI was 22.6cm. Fetal BPS was considered. (Figure 4).
Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapy第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 994. Differential diagnosisT h e p r e n a t a l d i f f e r e n t i a l d i a g n o s i s o f BPS depends on whether i t is intrapulmonary sequestration or extrapulmonary sequestration.Intralobar BPS has the characteristic of lacking normal communication with the tracheobronchial t ree and receiving i ts blood supply f rom the systemic circulation. It needs to be differentiated from congenital pulmonary airway malformation, congenital lobar overinflation, and congenital lobar emphysema and lung tumors.4.1 Congenital pulmonary airway malformation (CPAM)C PA M c a n h a v e a c o n n e c t i o n t o t h e tracheobronchial tree. The arterial supply and venous drainage of CPAM are from the pulmonary circulation.4.2 Congenita l lobar overinf lat ion (CLO)/ congenital lobar emphysema (CLE)Cr i t e r i a fo r CLO/CLE/bronch ia l a t r e s i a include hyperlucent lung postnatally, normal lung architecture, normal pulmonary vascularity, and absence of macroscopic cysts.4.3 Lung tumorsRare neoplasms, such as the pleuropulmonary blastoma (PPB) and the fetal lung interstitial tumor (FLIT), should also be considered as differential diagnosis. These tumors can be cystic and/or solid, with normal pulmonary vascularity. It has a well-demarcated fibrous capsule and no invasive features, without communication with the tracheobronchial tree.Extralobar BPS is more common on the left and appears solid. Most ELS drains to the systemic circulation through the azygous or hemiazygous vein or vena cava. Because of the systemic arterial supply and venous drainage, most BPS may develop severe left to right shunts, leading to high-output cardiac failure. BPS needs to be differentiated from neuroblastoma and adrenal hemorrhage.4.4 NeuroblastomaNeuroblastoma is most common on the right side. It can be cystic. Neuroblastoma may lead to elevated catecholamines, which result in maternal symptoms includes hypertension and tachycardia.4.5 Adrenal hemorrhageThe key to diagnosis of adrenal hemorrhage is the change in appearance over time. The initial appearance is that of an echogenic and solid- appearing lesion without internal blood flow. Subsequently, a hypoechoic central region develops, and then a more cystic appearance and a decrease in size are observed. In addition, BPS has a systemic feeding vessel whereas adrenal hemorrhage has no feeding vessel [3].5. TreatmentThe patient received dexamethasone for fetal lung maturation on 2023/06/28-29, and magnesium sulfate for fetal neuroprotection on 2023/06/29. Close monitoring of fetal condition was performed b y C T G a n d U S G . D u e t o f e t a l h e a r t a n d mediastinal compression, progressive increase in pleural effusion and presence of new ascites, intervention was considered necessary [4]. Since neonatal mortality substantially decreases after 32- 34 weeks of gestation, intervention by Cesarean delivery at gestational age of 30 weeks was not considered the best choice [5]. The patient was referred for intrauterine therapy on 2023/07/01 in Shenzhen.6. Outcome and fol low up Ultrasonography showed decreased fe ta l pleural effusion on 2023/07/01, which might be due to the effect of Dexamethasone [6]. This fetus underwent intrauterine thoracentesis on 2023/07/01. A total of 25ml pleural fluid was drained.
Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapy澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal100Figure 5.Figure 6.After intrauterine thoracentesis, daily control USG showed gradually increasing pleural effusion. Dexamethasone was given again with close monitoring This fetus was delivered by Caesarean section on 2023/08/21 (GA38+2week) in Hong Kong with an APGAR score of 9-10-10. The newborn baby boy did not need oxygen therapy after delivery. His chest X-Ray and chest ultrasonography showed mild left pleural effusion. He was closely observed in an incubator and was given intravenous infusion of antibiotic (Penicillin) for 7 days. His left pleural effusion had decreased after treatment. Repeat of pleural effusion by USG. (Figure 5) Treatment target was to extend the gestational age to term or near term.chest X-Ray at 17 day-old showed no marked mass, nodule or parenchymal infiltration noted in the both lungs. Bilateral phrenic surfaces and costophrenic angles are clear. (Figure 6)The baby’s clinical condition was considered to be good, with no shortness of breath or cyanosis. He was well on breast feeding with subsequent normal growth and development.
Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapy第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 1017. DiscussionBPS is a rare congenital malformation, with pathogenesis not fully understood. The diagnosis depends on ultrasound examination, with BPS appearing as a hyperechoic mass in the thorax. The fetus with BPS rarely develops pleural effusion with mediastinal shift. A large BPS is defined by CVR>1.6. [7] In general, a fetus with a large BPS who develops hydrops in the second trimester is likely to have a poor prognosis, such as fetal demise, very or extremely preterm bir th and pulmonary hypoplasia. If tension hydrothorax or cardiac decompensation with hydrops develops, thoracoamniotic shunting or thoracentesis may have to be considered as a temporizing maneuver [8].Thoraco-amniotic shunting and thoracentesis are well-established treatment for fetal pleural effusion. The goals of these therapies are to reverse the hydrops, relieve lung compression and prolong the pregnancy, thus avoiding fetal death, reducing the risks of prematurity and allowing for definitive neonatal treatment. Thoracentesis is single-use for drainage of the pleural effusion. I n i t i a l l y f o r t r e a t m e n t o f p l e u r a l e f f u s i o n , thoracentesis should be performed to drain and then re-evaluate to determine how rapidly the pleural fluid reaccumulates. Thoraco-amniotic shunting is chronic drainage of the pleural effusion. The selection criteria for thoracoamniotic shunting includes rapid recurrence of the effusion after thoracentesis, and gestational age of <32 weeks. However, we need to know that thoracoamniotic shunting carries a significantly higher risk than thoracentesis. The reported rate of fetal demise after shunt placement and initial thoracentesis is estimated to be 38% and only 0.5-1.0% respectively [9].This case was diagnosed as BPS by USG which showed progressive hydrothorax with mediastinal and cardiac shift in the fetus.[10] We performed multiple interventions after Multi-Disciplinary team (MDT) discussion with the aim of improving perinatal outcomes. These included steroid for fetal lung maturation and intrauterine thoracocentesis. We o b s e r v e d s i g n i f i c a n t i m p r o v e m e n t o f hydrothorax and mediastinal shift in the fetus after treatment.Delivery planning should be in conjunction with Neonatology and Pediatric Surgery. If the lung mass has resolved or is small with no mediastinal shift or hydrops, BPS itself is not an indication for early delivery or Cesarean birth. For fetuses with large masses that cause mediastinal shift and/or hydrops, delivery should be planned for in a tertiary care center equipped with neonatal intensive care unit capable of resuscitation of neonates with respiratory difficulties, together with Pediatric surgeons experienced in care of these infants [11].In the absence of other significant congenital anomalies, the prognosis of BPS is generally favorable unless there is associated hydrothorax or hydrops. We stress the importance of regular prenatal care to identify the existence of any fetal malformation. Intrauterine therapy for BPS is aimed at prolonging gestational age to minimize the risk of preterm delivery and decrease neonatal mortality [12].8. References[1] Witlox RS, Lopriore E, Opekes D. Prenatal interventions for fetal lung lesions. Prenat Diagn 2011; 31:628–36 [2] Nunes C, Pereira I, Araújo C, Santo SF, Carvalho RM, Melo A, Graça LM. Fetal bronchopulmonary malformations. J Matern Fetal Neonatal Med. 2015 Nov;28(16):1996-2000. doi: 10.3109/14767058.2014.984603. Epub 2014 Dec 4. PMID: 25394612.[3] Hellmund A, Berg C, Geipel A, Bludau M, Heydweiller A, Bachour H, et al. Prenatal diagnosis and evaluation of sonographic predictors for intervention and adverse outcome in congenital pulmonary airway malformation. PLoS One (2016) 11(3): e0150474.10.1371/journal.pone. 0150474
Fetal bronchopulmonary sequestration with pleural effusion and intrauterine therapy澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal102[4] Chen J.S.C., Walford N., Yan Y.L., Ong C.L., Yeo G.S.H. Foetal intralobar lung sequestration: Antenatal diagnosis and man- agement. Singap. Med. J. 2003; 44:630–634.[5] Cavoret to P, Molina F, Poggi S, e t a l . P r e n a t a l d i a g n o s i s a n d o u t c o m e o f echogenic fetal lung lesions. Ultrasound Obstet Gynecol 2008; 32:769–83[6] Guenot C, Dubrit K, Lepigeon K, et al. E ffec t o f ma te rna l be tamethasone on hydrops f e t a l i s caused by ex t r a loba r pulmonary sequestration: a case report. J ObstetGynaecol 2019; 39:120.[7] Crombleholme TM, Coleman B, Hedrick H, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg 2002; 37:331–8.[8] Litwinska M, Li twinska E, Szaf l ik K, Debska M, Szajner T, Janiak K, Kaczmarek P, Wielgos M. Management Options for Fetal Bronchopulmonary Sequestration. J Clin Med. 2022 Mar 20;11(6):1724. doi: 10.3390/jcm11061724. PMID: 35330048; PMCID: PMC8954010.[9] Johnson, M. P., & Wilson, R. D. (2017). Shunt-based interventions: Why, how, and when to place a shunt. Seminars in Fetal and Neonatal Medicine, 22(6), 391–398. doi: 10.1016/j.siny.2017.09.006 [10] Hernanz-Schulman M., Stein S.M., Neblett W. W. , A t k i n s o n J . B . , K i r c h n e r S . G . , Heller R.M., Merrill W.H., Fleischer A.C. Pulmonary sequestration: Diagnosis with color Doppler sonography and a new theory of associated hydrothorax. Radiology. 1 9 9 1 ; 1 8 0 : 8 1 7 – 8 2 1 . d o i : 1 0 . 1 1 4 8 /radiology.180.3.1871300.[11] Seravalli, V., Miller, J. L., Block-Abraham, D . , & Bascha t , A . A . (2016) . Duc tus venosus Doppler in the assessment of fetal cardiovascular health: an updated practical approach. Acta Obstetricia et Gynecologica Scandinavica, 95(6), 635–644. doi:10.1111/aogs.12893[12] Divjak N, Vasseur Maurer S, Giannoni E, Vial Y, de Buys Roessingh A, Wildhaber BE. Bronchopulmonary Sequestration with Morbid Neonatal Pleural Effusion despite Successful Antenatal Treatment . Front Pediatr. 2017 Dec 4; 5:259. doi: 10.3389/f p e d . 2 0 1 7 . 0 0 2 5 9 . P M I D : 2 9 2 5 5 7 0 2 ; PMCID: PMC5722982
I Sam LOI et al.第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 103Mimics of inguinal hernia in pregnancy: round ligament varicosities I Sam LOI*, Chin Wan LEONG, Jose COSTA MAIADepartment of Surgery, Conde de São Januário General hospital, Macau *Correspondence to: I Sam LOI, glorialoi@yahoo.com.hkAbstractRound ligament varicosities (RLV) are more commonly seen in pregnant women than in the general population and pose diagnostic challenges as they are not easily distinguishable from inguinal hernias. This case report highlights the RLV anatomy and their significance in pregnancy, relevant clinical features, imaging characteristics and potential complications. We aim to raise awareness of RLV in order to avoid unnecessary surgical procedures. Keyword: Round ligament varicosities; Inguinal mass in pregnancy; Inguinal hernia1. IntroductionInguinal swelling and pain during pregnancy a re more commonly a t t r ibu ted to RLV than hernias[1]. RLV more frequently present during the second trimester [2] and before the emergence of ultrasonography were often misdiagnosed as hernia. The distinction between RLV and inguinal hernia is crucial, as RLV do not require surgery while inguinal hernias do. Currently, ultrasonography remains the imaging modality of choice for the diagnosis of RLV.2. Case presentation A 26 year-old Chinese woman, Gravi ty1 Parity 0, presented to the emergency department at gestational age (GA) of 26+4 weeks, complaining of left painful inguinal bulge which was reducible on supine position but increasing in size on standing s ince GA 24 weeks. There was no his tory of obstructive gastrointestinal symptoms. Past history and routine prenatal care were unremarkable. Physical examination revealed a left inguinal mildly tender mass with an approximate size of 4x2cm, which was bulging upon Valsalva maneuver, but spontaneously reducing on supine position. The radiologist made an initial diagnosis by ultrasound of a left, ovary-containing inguinal he rn i a u s ing g rey sca l e imag ing . Howeve r, considering her gestational age and uterine volume, her ovaries should be located within the peritoneal cavity, as confirmed by the obstetricians using transabdominal ultrasonography. (Figure 1) Since there were no evidence supporting the init ial sonographic diagnosis and no signs of strangulation o r i n c a r c e r a t i o n r e q u i r i n g u rg e n t s u rg i c a l management, the patient was advised to follow up 1 week later.
Mimics of inguinal hernia in pregnancy: round ligament varicosities 澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal104Figure 1. Figure 2a. Figure 1. Bilateral ovaries (labeled ROV and LOV for right ovary and left ovary, respectively) were identified in the peritoneal cavity using transabdominal ultrasonography. The absence of bowel or omental contents made the diagnosis of hernia unlikely. Figure 2b. Figure 2c.Figure 2c. M-Mode sonography demonstrated a venous flow pattern which is consistent with RLV.On review a t GA 27+4 weeks , the groin swell ing persis ted with occasional pain af ter walking for a long time. Color Duplex Doppler sonography was repeated in supine posi t ion, followed by Valsalva maneuver. (Figure 2a) A hypoechoic 3.8cm x 0.7cm x 1.8 cm structure with a peripheral cystic zone, not connected to the peritoneal cavity, was identified. It migrated to the inguinal region more prominently on erect position and Valsalva maneuver. (Figure 2b) On color Doppler flow imaging (CDFI), multiple dilated varicosities around the round ligament with increased blood flow on standing and Valsalva maneuver were compatible with RLV (Figure 2a, Figure 2b, Figure 2c).
Mimics of inguinal hernia in pregnancy: round ligament varicosities 第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 105Figure 3. Figure 3. The patient was treated conservatively and underwent an uneventful cesarean delivery a t G A 3 9 + 5 w e e k s d u e t o c e p h a l o p e l v i c disproportion. She was subsequently reviewed at 12 weeks post-delivery. Despite the relief of her symptoms, follow-up ultrasonography (Figure 3) still showed the presence of RLV, with dimensional regression (2.1cm x0.7cmx0.6cm). Eventually, on further follow-up, the mass was undetectable after 1 year postpartum. 3. Discussion R o u n d l i g a m e n t v a r i c o s i t i e s ( R LV ) a r e prominent veins within the round ligament, a c l in ical ent i ty f i rs t descr ibed by Verovi tz in 1941. [3] A case series by McKenna suggests the incidence of RLV to be 0.13%, whereas incidence of inguinal hernia during pregnancy was reported to be 0.03–0.1% [4]. A recent systematic review by Md Mahfooz et al. comprising 48 studies identified the mean age of patients at 30.65 years and 60.2% of them were Asian. Around half of them presented with a painful lump over the groin area while no maternal mortality or fetal complications were reported. [5]Since most of the intra-abdominal structures which could potentially migrate into the hernia sac are pushed aside by the enlarging uterus, it is uncommon for inguinal hernia to appear de novo during pregnancy. [6] RLV formation during pregnancy is mainly promoted by the enlarging uterus and, being self-limiting, is therefore not an indication for surgical management. One-third of RLV were reported to be bilateral and approximately 17% of cases presented during the postpartum period. [2] There are a number o f d i ffe ren t ia l d iagnoses fo r g ro in swel l ing including femoral hernia, lymphadenopathy or other pathologies involving the inguinal canal and round ligament. In the presence of pain, the clinical suspicion for hernia incarceration is high.Ana tomica l ly, t he round l i gamen t , a l so known as ligamentum teres uteri , is one of the uterine supporting structures, extending from the anterolateral aspect of the uterus anteriorly between the layers of the broad ligament. It travels from the lateral aspect of the uterus to the internal inguinal ring, along the inguinal canal and terminates at the labia majora, where it anchors the uterus. RLV arise from the veins that drain the round ligament and inguinal canal into the inferior epigastric vein. Generally, pregnancy precipitates the formation of RLV due to the presence of the fol lowing underlying physiological adaptations:a) Increased progesterone levels cause smooth muscle relaxation resulting in venous dilation. b) Increased intraabdominal pressure caused by the gravid uterus results in pelvic venous engorgement. c) Increased venous return caused by the raised cardiac output Clinical ly, both inguinal hernia and RLV share several characteristics, which make them difficult to be distinguished when uncomplicated. Similar to inguinal hernia, RLV could be either reducible, given the valveless nature of veins that allows complete emptying, or irreducible if only partial emptying occurs with positional change. In addition, the distinction between a thrombosed RLV and a non-reducible inguinal hernia becomes even more difficult as both present as an irreducible, erythematous and tender groin mass. Radiologically, an indirect hernia has a similar anatomical course as a RLV. Both arise lateral
Mimics of inguinal hernia in pregnancy: round ligament varicosities 澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal106Thrombosis is highly suspected in the absence of flow signal on color Doppler with no change in size and morphology of the hypoechoic structures on Valsalva and on erect/supine positioning. Under such circumstances, further imaging, like CT or MRI is warranted. To our knowledge, there are only two case reports of thrombosed RLV with CT and MRI images in postpartum women in the English medical literature [7][8]. Features like pre-contrast hyperdensity, presence of surrounding fat stranding and lack of enhancement on post-contrast CT illustrate the imaging appearance of thrombosed RLV. On MRI, RLV appear as a dilated serpentine structure in the inguinal canal. In case of thrombosis, it shows high T1 signal and low T2 signal. [7] With the relief of pelvic venous obstruction a f t e r d e l i v e r y, m o s t c a s e s o f R LV r e s o l v e spontaneously. Nevertheless, despite surveillance b e i n g t h e m a i n s t a y o f a p p r o a c h , p o t e n t i a l complications, such as hemorrhage secondary to variceal rupture and acute thrombosis should be excluded, especially if pain is the predominant symptom. In a case review ser ies of Engl ish literature [2], only 1 out of the 26 reported cases was complicated by thrombosis. To the best of our knowledge, there is no consensus on the management of RLV thrombosis. However, a case was resolved by subcutaneous low molecular weight heparin (LMWH) 40 mg daily for 6 weeks [8].Overall , ultrasonography, when compared to CT and MRI, provides an additional benefit for pregnant women in terms of lack of radiation exposure and easy accessibil i ty. Moreover, i t provides a dynamic assessment, which allows characterization of inguinal canal contents on certain maneuvers like Valsalva or cough impulse. It is not only useful for diagnosis, but also plays a crucial role in exclusion of complications including venous thrombosis and the potential development of May Thurner syndrome. 4. Conclusion The major objective of our presentation is to distinguish between inguinal hernia and round l igament varicosit ies (RLV) occurring during pregnancies, as conservative management is the main approach for the latter diagnosis. With a tendency towards conservat ive management , failure to recognize this condition may expose both the mother and fetus to avoidable surgical risks. Therefore, RLV should be taken into account as part of the differential diagnosis in any pregnant woman who presents with inguinal swelling. Since Table 1. Comparison of sonographic features between inguinal hernia and RLVInguinal Hernia Round ligament varicose (RLV) a) Presence of peritoneal wall defect in hernia a) Presence of multiple dilated veins passing through the inguinal canalb) Presence of hernia contents-omentum, bowel or urinary bladder-peristalsis, mesenteric fat b) Absence of bowel/lymph nodes in the inguinal massc) Drainage of veins into the inferior epigastric veinto the inferior epigastric vessels and travel to the labia majora through the inguinal canal. On ultrasonography, RLV exhibits multiple hypoechoic serpentine structures in the subcutaneous layer with “a bag of worms” appearance, while on CT, it appears as a hyperdense serpentine structure extending from the deep inguinal ring along the inguinal canal to the labia majora.The following table compares the difference between RLV and inguinal hernia on ultrasonography:
Mimics of inguinal hernia in pregnancy: round ligament varicosities 第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 107the diagnosis of RLV cannot rely solely on clinical grounds, the readily available ultrasonography plays an indispensable role to provide a prompt and accurate diagnosis without exposure to radiation. In the case of an erythematous and tender mass, advanced imaging techniques, most preferably MRI, should be considered to distinguish between incarceration and thrombosis.5. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. The patient understands that due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. 6. Confl icts of interestThere are no conflicts of interest. 7. References[1] Lechner M, For te lny R, Öfner D, e t a l . Suspected inguinal hernias in pregnancy―handle with care![J]. Hernia, 2014, 18(3): 375-379.doi: 10.1007/s10029-013-1082-y.[2] Ry u K H , Yo o n J H . U l t r a s o n o g r a p h i c diagnosis of round l igament varicosi t ies mimicking inguinal hernia: report of two cases with literature review[J]. Ultrasonography, 2 0 1 4 , 3 3 ( 3 ) : 2 1 6 - 2 2 1 . d o i : 1 0 . 1 4 3 6 6 /usg.14006[3] Tomkinson J S, Winterton W R. Varicoceles of the round ligament in pregnancy, simulating inguinal herniae[J]. British Medical Journal, 1 9 5 5 , 1 ( 4 9 1 8 ) : 8 8 9 - 8 9 0 . d o i : 1 0 . 11 3 6 /bmj.1.4918.889.[4] McKenna D A , Ca r t e r J T, Pode r L , e t al . Round l igament varices: sonographic appearance in pregnancy[J]. Ultrasound in Obstetrics and Gynecology: The Official Journa l o f the In te rna t iona l Soc ie ty o f Ultrasound in Obstetrics and Gynecology, 2008, 31(3): 355-357.doi: 10.1002/uog.5271.[5] Mahfooz M B,Al S N,Al A S. Round ligament varicosity: a rare but important differential diagnosis of groin lumps during pregnancy.[J]. British journal of hospital medicine (London, England : 2005),2023,84(5).doi: 10.12968/hmed.2022.0469[6] Mine Y, Eguchi S, Enjouji A, et al. Round ligament varicosities diagnosed as inguinal hern ia dur ing pregnancy: A case repor t and series from two regional hospitals in Japan[J]. International journal of surgery case reports, 2017, 36: 122-125.doi: 10.1016/j.ijscr.2017.05.006.[7] To k u e H , A o k i J , Ts u s h i m a Y, e t a l . Charac te r i s t ic of computed tomography and magnetic resonance imaging f inding o f t h r o m b o s e d v a r i c e s o f t h e r o u n d l igament of the uterus: a case report[J] . Journal of computer assisted tomography, 2 0 0 8 , 3 2 ( 4 ) : 5 5 9 - 5 6 1 . d o i : 1 0 . 1 0 9 7 /RCT.0b013e318133a9f1.[8] Ng C, Wong G T. Round ligament varicosity thrombosis present ing as an i r reducib le inguinal mass in a postpartum woman[J]. Journal of Clinical Imaging Science, 2019, 9:28. doi: 10.25259/JCIS-19-2019
Isabel CVP AFONSO et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal108Two clinical cases of 46xy karyotype in phenotypic females: disorders of sex development or a different diagnosis?Isabel CVP AFONSO*, Kin Veng KOON, Wai CHIN, In Fong LAMAbstractInterpretation on laboratory results mostly depends on clinical information on the laboratory request forms. We intend to draw the attention to the importance of providing comprehensive clinical information on the request forms to laboratory through reviewing two cytogenetic reports from two individual cases. Two female patients were classified as 46XY karyotype during investigation for primary amenorrhea and recurrent miscarriage respectively. The inconsistency of sex chromosome and clinical phenotype is subsequently confirmed to be induced by bone marrow transplant instead of disorders of sex development. Keyword: Disorders of sex development; Karyotype; Bone marrow transplant Department of Clinical Pathology, Conde de São Januário General hospital *Correspondence to: Isabel CVP Afonso, Department of Clinical Pathology, Conde de São Januário General hospital, celinaafonso@gmail.com1. IntroductionClinical Pathology (Serviço de Patologia Clínica, SPC) of Centro Hospitalar Conde de São Januário General hospital, Macau is the department that serves both the hospital and Health Centers in Macau for biological laboratory tests. As with most other laboratories around the world, not all kind of tests are available in our department and some need to be send out to other reference laboratories for testing. Currently we send out samples to different hospitals and laboratories such as in Hong Kong and America, as a dispatch service in SPC. Chromosomal studies requested by Obstetrics & Gynecology and Pediatrics are usually sent to Hong Kong. We have encountered two cases of karyotype results which showed that the sex chromosomes are opposite to the patients’clinical characteristics. 2. Case presentationCase 1 - Primary amenorrhea misdiagnosed as Disorders of Sex DevelopmentThis is a case of a girl who was referred to Gynecology OPD in 2020 for primary amenorrhea at 15 years of age. Routine laboratory tests showed low level of Estradiol (E2), and high level of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Thyroid Stimulating Hormone (TSH) which were consistent with ovarian failure. Advanced tests such as cytogenetic test was also required to check and confirm the diagnosis. The cl inical information provided on the laboratory request form was: “A 15-year-old female, no menarche; compound heterozygous state for Hemoglobin E and β thalassemia on regular blood transfusion since she was three years old”. The result of Cytogenetic test came back was: “Karyotype 46XY” with the comment “Conventional cytogenetic analysis of cultured lymphocytes
Two clinical cases of 46xy karyotype in phenotypic females: disorders of sex development or a different diagnosis?第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 109showed a male karyotype. Quantitative fluorescent PCR result showed presence of SRY gene. Further workup for Disorders of Sex Development and genetic counseling are recommended”. Following review by clinical pathologists in our department, additional information from the medical record of Gynecology OPD in Health Information System (HIS) revealed that “the patient presented as morphologically female, with mild breast enlargement in Tanner stage 2 and no pubic hair or axilla hair in Tanner stage 1; and normal vulva and vagina opening, but no uterus or adnexa was palpable by rectal examination. Ultrasound showed presence of the vagina but absence of uterus or bilateral ovaries in pelvis”. We were curious and surprised with the above results, and wondered if this is a possible case of Disorders of Sex Development (DSD). At that juncture, there were two notable points of concern- amenorrhea and karyotype. By further reviewing from the patient’s history, it was found that: 1. During pregnancy of the patient’s mother, amniocentesis was performed due to mother’s advanced age. The resul t of the fetus’s ( this patient’s) karyotype was “46XX”. 2 . However, the pa t ien t underwent bone marrow transplantation (BMT) when she was six years old for treatment of her double heterozygous β tha lassemia /hemoglob in E condi t ion . The donor was her elder brother with matched HLA typing. After BMT, the patient became transfusion independent since.After giving this additional information to the referral laboratory by our department, the patient’s karyotype report was corrected as: “The karyotype is consistent with the updated clinical information that this patient underwent matched sibling bone marrow transplant from her elder brother in 2011”. A f t e r B M T, t h e p a t i e n t h a d u n d e rg o n e c h e m o t h e r a p y i n c l u d i n g B u s u l p h a n , Cyclophosphamide and anti-thymocyte globulin until 2013. As Busulphan and Cyclophosphamide are alkylating agents, they are known to cause ovarian failure and prevent the onset of puberty. Hormone replacement therapy (HRT) was subsequently given to the patient who had her menses under HRT finally.Case 2 – Recurrent abortion and Disorder of Sex Development?This is a case of a 37-year-old female patient presented to Gynecological OPD in 2017 with a history of recurrent miscarriage (G4P1A3) in the past two years. In the course of investigation for recurrent abortion, a sample of the patient was sent for karyotyping. The result was: “46XY, PCR study showed presence of SRY and normal numbers of chromosomes 13, 18, 21 and XY in this sample. The karyotype is inconsistent with the referral indication.” Following review of the patient’s history by our department, it was found that the patient u n d e r w e n t m a t c h e d s i b l i n g b o n e m a r r o w transplantation when she was twenty years old in 1999 for treatment of her aplastic anemia, and the donor was her brother. With this additional clinical information provided to the referral laboratory, a final report of the patient was issued as “The karyotype can be related with the supplementary clinical information that following engraftment post bone marrow transplantation. The peripheral blood genotype is identical to that of the donor”. 3. DiscussionDisorders of sex development (DSD) were defined as congenital conditions within which the development of chromosomal, gonadal and anatomic sex is atypical at the Chicago Consensus Meeting in 2006 [1]. Laboratory investigations play a key role in the diagnostic workflow in individuals with suspected DSD. The conventional cytogenetic and molecular ana lyses inc lude karyotyping and fluorescence in situ hybridization (FISH) or Quantitative fluorescent PCR for Sex-determining region Y protein (SRY) gene in the blood sample are the common laboratory tests for the initial investigation of DSD [1,2].
Two clinical cases of 46xy karyotype in phenotypic females: disorders of sex development or a different diagnosis?澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal110In the category of XY DSD, major i ty of patients may present with clinical characteristics of primary amenorrhea, absence of secondary sex characters and abnormal hormone level [1]. A female adolescent appearance with primary amenorrhea will raise suspicion of DSD and a 46XY karyotype seems to give a solid evidence to the category of XY DSD. Under the circumstance of sex-mismatched b o n e m a r r o w t r a n s p l a n t f o r p a t i e n t s , s e x chromosome can be changed to the opposi te . Similar case reports have been published about patient having changed to opposite sex chromosome in karyotype after sex-mismatched BMT. Most of the patients suffered from high risk or poor prognosis of acute leukemia [3-6]. Since BMT is an indication not only in leukemia and lymphoma, but also in severe aplastic anemia, blood transfusion-dependent thalassemia as well as autoimmune disease, change in sex chromosome in karyotype became more commonly reported as a result [7,8]. In case 1, considering her medical history which revealed that the patient had undergone a sex-mismatched BMT and chemotherapy, we infer that her karyotype of peripheral blood result 46XY was caused by BMT. Amenorrhea and delay of second sex characteristics were caused by chemotherapy. Both Busulfan and Cyclophosphamide are alkylating agents, which prevent cell division by interacting with DNA, are known to be associated with the occurrence of ovarian failure. [9-14]. The 46XX karyotype detected by maternal amniocentesis when she was a fetus is also an undeniable fact conf i rming tha t the pa t ien t i s a female . For cases where there are no pre-BMT karyotype for comparison, a somatic cell or germ cell karyotype will give stronger evidence to support the diagnosis. After BMT, since hematopoietic stem cells have been transplanted, the chromatids of hematopoietic cel ls wil l become the donor’s chromosomes, although the chromosomes of the patient’s somatic cells will not be changed. In case 2, it is unthinkable to presume that the patient has DSD since she had already been pregnant several times and had delivered a baby previously. Her 46XY karyotype could also be explained by the change in sex chromosome caused by BMT. In these two cases , c l in ica l pa thologis ts work closely with clinicians whose contribution to referral service is crucial . The importance of deta i led medical h is tory a lso needs to be reinforced. A correct diagnosis of the patients’ disease condition depends on not only the clinical manifestation and physical examination of the patient, but also their present and past medical history and careful interpretation of laboratory tests. 4. ConclusionProviding comprehensive clinical information on the request form to laboratory is extremely essential for making a correct interpretation on the results. Failing which, it can lead to possible diagnost ic confusion at f i rs t impression, and even more seriously to erroneous and/or delayed diagnosis, investigation or treatment. 5. References[1] Hughes IA, Houk C, Ahmed SF, et a l . Consensus s t a t emen t on managemen t o f in te r sex d i sorders . J Ped ia t r Uro l . 2006;2(3):148–62.[2] Se lma Feldman Witchel . Disorders of sex development . Best Pract Res Cl in Obstet Gynaecol. 2018 April; 48: 90–102. doi:10.1016/j.bpobgyn.2017.11.005.[3] Dania Al-Jaroudi and Ayah Hijazi . XY C h r o m o s o m e i n A c u t e Ly m p h o c y t i c L e u k e m i a F e m a l e w i t h S e c o n d a r y Amenorrhea. Cancer Sci Res Open Access 2(1): 1-3. Cancer Sci Res Open Access 2(1): 1-3. ht tp: / /dx.doi .org/10.15226/csroa.2015.00113. [4] H e H u a n g a n d Q i n j i e Ti a n . P r i m a r y a m e n o r r h e a a f t e r b o n e m a r r o w
Two clinical cases of 46xy karyotype in phenotypic females: disorders of sex development or a different diagnosis?第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 111transplantation and adjuvant chemotherapy m i s d i a g n o s e d a s d i s o r d e r o f s e x d e v e l o p m e n t . M e d i c i n e ( B a l t i m o r e ) . 2016 Nov; 95(44): e5190. doi: 10.1097/MD.0000000000005190.[5] Mouna Elleuch et al., Misdiagnosed 46, XY DSD after Bone Marrow Transplantation in a Female with Acute Lymphoblastic Leukemia and Secondary Amenorrhea. EAS J Biotechnol Genet; Vol-2, Iss-3 (May-June, 2020): 20-23. doi: 10.36349/easjbg.2020.v02i03.001.[6] Zhang et al . Live birth in woman with premature ovarian insufficiency and 46, XY karyotype after chemotherapy and bone marrow transplant: a case report. BMC Pregnancy and Childbirth (2023) 23:170. doi:10.1186/s12884-023-05464-1.[7] J e r z y H o l o w i e c k i . I n d i c a t i o n s f o r hematopoietic stem cell transplantation. Pol Arch Med Wewn. 2008 Nov;118(11):658-63. doi: 10.20452/pamw.516.[8] Keith M. Sullivan, Robertson Parkman, M a r k C . W a l t e r s . B o n e M a r r o w Transplantation for Non-Malignant Disease. H e m a t o l o g y A m S o c H e m a t o l E d u c Program. 2000;319-338. doi : 10.1182/asheducation-2000.1.319.[9] Bakker B, Oostdijk W, et al. Disturbances o f g r o w t h a n d e n d o c r i n e f u n c t i o n a f te r busu l fan-based condi t ion ing for haematopoietic stem cell transplantation during infancy and childhood. Bone Marrow Transplant. 2004 May;33(10):1049-56. doi: 10.1038/sj.bmt.1704481.[10] Afify A, Shaw PJ, e t a l . 2004 Growth and endocrine function in children with a c u t e m y e l o i d l e u k e m i a a f t e r b o n e marrow transplantation using busulfan/c y c l o p h o s p h a m i d e . B o n e M a r r o w Transplant. 2000 May;25(10):1087-92. doi: 10.1038/sj.bmt.1702384.[11] Desmeules P, Devine PJ. Characterizing the ovo tox ic i ty o f cyc lophosphamide metabolites on cultured mouse ovaries. Toxicol Sci 2006;90:500–509. doi:10.1093/toxsci/kfj086.[12] Barton SE, Najita JS, et al . Inferti l i ty, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohor t . Lancet Oncol . 2013;14(9): 873–881. doi: 10.1016/S1470-2045(13)70251-1.[13] Sklar CA, Mertens AC, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst. 2006;98(13):890–896. doi: 10.1093/jnci/djj243.[14] W Chemaitilly et al. Acute Ovarian Failure in the Childhood Cancer Survivor Study. The Journal of Clinical Endocrinology & Metabol i sm, Volume 91, I ssue 5 , 1 May 2006, Pages 1723–1728, https://doi.org/10.1210/jc.2006-0020.
Ut Man IONG et al.澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal112COVID-19 infection induced acute laryngitis or laryngitis caused by SARS-CoV-2/Omicron variant infectionUt Man IONG, Ki Man PAI*, Xian Zhong WANG, Xin Ye CHEN, Wan Pang SAM, Tin Seak MOK, Guo Liang ZHANG, Chon Man KAN, Cheong Un SIO, Kit Ian LIO AbstractCOVID-19, caused by the novel coronavirus SARS-CoV-2, typically presents with common symptoms such as fever, cough, and shortness of breath. However, there have been reports of COVID-19 affecting the larynx, leading to a condition known as COVID laryngitis. The Omicron variant of COVID-19 is known for its reduced affinity for the lower respiratory tract. Instead, it often manifests with upper respiratory tract symptoms like nasal discharge and sore throat. This study examines the diagnostic role of laryngoscopy in evaluating COVID laryngitis through a case report of a 74-year-old female presenting with symptoms of shortness of breath and sore throat. The patient’s condition was diagnosed through laryngoscopy, and appropriate treatment led to a significant improvement in symptoms, avoiding the need for urgent intubation or tracheostomy.Keywords: SARS-COV-2; Laryngitis; upper AIRWAY OBSTRUCTION; Tracheostomy; Airway managementConde de São Januário General hospital, Department of Otolaryngology, Macau*Correspondence to: Ki Man PAI, paikiman@gmail.com1. IntroductionCOVID-19, caused by the novel coronavirus SARS-CoV-2, primarily presents as a respiratory i l lness. While fever, cough, and shortness of breath constitute the most common symptoms, there have been documented cases of COVID-19 affecting the larynx, leading to a condition referred to as COVID laryngitis. Notably, the Omicron variant of COVID-19 demonstrates a reduced affinity for the lower respiratory tract. Instead, this variant is characterized by upper respiratory tract symptoms, such as nasal discharge and sore throat. Consequently, in cases of laryngeal stenosis, assessing disease severity through blood oxygen saturation levels has proven less informative [1].Laryngoscopy emerges as a valuable diagnostic tool when evaluating COVID laryngitis. It enables direct visualization of the larynx and vocal cords, facilitating precise assessment and diagnosis.2. Case reportWe present a case of ‘COVID laryngitis’ in a 74-year-o ld female dur ing the Omicron epidemic peak in Macao at the end of 2022 [2]. The patient arrived at the emergency department with complaints of shortness of breath, hoarseness, sore throat, and difficulty speaking for the past two days. She had a medical history of hypertension, diabetes, and dyslipidemia, with no significant allergies or recent travel.During the physical examination, the patient exhibited a hoarse voice, dyspnea, and pronounced inspiratory stridor. Laryngoscopy, performed with standard disinfection procedures to prevent disease
COVID-19 infection induced acute laryngitis or laryngitis caused by SARS-CoV-2/Omicron variant infection第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 113transmission, revealed erythema and edema of the larynx, along with glottis stenosis consistent with a diagnosis of COVID laryngitis (Figure 1 & 2). A COVID-19 test confirmed the infection.Treatment commenced with a pulse steroid intravenous therapy of hydrocortisone (200mg every 8 hours) for three days, and the patient was advised to rest her voice. She was admitted to the ward for symptom monitoring in case of respiratory distress.Ove r t he nex t t h r ee days , t he pa t i en t’s symptoms s ign i f i can t ly improved , w i th t he resolution of hoarseness and sore throat. Subsequent laryngoscopy on Day 3 after admission revealed the disappearance of laryngeal swelling, erosion, and synechia (Figure 3). The patient did not experience any respiratory distress during her hospital stay.For continued management, the patient was prescribed steroid inhalers (Beclometasone oral inhalation, 2 puffs three times a day) for five days. Upon follow-up in our outpatient department after one month, she had fully recovered without any notable sequelae (Figure 4).Figure 1. Figure 2.Figure 1. Laryngoscopic findings. The larynx and hypopharynx showed erythema and edema with vocal cord synechia.Figure 2. Swelling and erosion formed form the glottis to the sub-glottis.Figure 3. Figure 4.Figure 3. The laryngeal swelling, erosion and previous synechia dissolved.Figure 4. Totally recovered without notable sequela in larynx.
COVID-19 infection induced acute laryngitis or laryngitis caused by SARS-CoV-2/Omicron variant infection澳門醫學雜誌 Revista Médica de Macau Macao Medical Journal1143. DiscussionAccording to the World Health Organization’s (WHO) guidelines on COVID-19 treatment, the use of antiviral drugs is recommended for non-severe COVID-19 patients who are at the highest risk of hospitalization. Individuals at higher risk typically include those who are unvaccinated, elderly, or have compromised immune systems or chronic diseases [3].In cases of acute inflammation involving upper respiratory tract stenosis, such as the one presented here, the primary choice for symptomatic treatment is systemic corticosteroids due to their potent anti-inflammatory properties. However, it’s important to note that corticosteroids are not recommended for COVID-19 patients who do not require oxygen therapy [4].Therefore, vigilance is crucial in identifying symptoms indicative of upper airway stenosis. Delayed detection of laryngeal stenosis can lead to severe consequences, especially when it comes to administering steroids. If there are concerns about upper airway obstruction during the patient’s presentation or if stenosis worsens despite steroid treatment, emergency airway management becomes necessary.Emergency a i rway managemen t op t ions encompass tracheostomy, cricothyrotomy, and tracheal intubation. It’s essential to recognize that all these methods for managing COVID-19 carry a high risk of generating aerosols, which can pose an infection risk to healthcare workers. Therefore, these procedures must be performed under strict infection control measures [5].4. Conclusion“C O V I D - 1 9 t y p i c a l l y m a n i f e s t s w i t h predominantly lower airway inflammation and mild upper airway involvement. However, clinicians should maintain a high suspicion for upper airway stenosis when patients present with symptoms such as ‘muffled speech’,‘dysphagia’,‘severe pain on swallowing’, or ‘inspiratory dyspnea or stridor’[6].Hence, it is imperative to conduct laryngeal and pharyngea l eva lua t ions us ing a f lex ib le l a ryngoscope whi le adher ing to appropr ia te in fec t ion con t ro l measures . Th i s i s c ruc ia l , considering the potential progression to l i fe-threatening laryngeal stenosis, as observed in this case. Acute airway stenosis constitutes a critical and urgent condition. In patients experiencing acute airway stenosis, a sudden drop in blood oxygen saturation signifies an immediate risk of airway obstruction. This principle is particularly applicable in COVID-19 cases.However, it’s worth noting that the severity of COVID-19 cases is often primarily assessed based on pneumonia symptoms, typically determined by monitoring blood oxygen saturation levels. Cases of upper airway stenosis accompanied by laryngitis, even when blood oxygen levels have not yet decreased, as in the current case, may still be categorized as mild COVID-19. Consequently, such cases might not initially qualify for hospitalization or emergency transport.With the prevalence of the Omicron variant, there has been an increase in the number of cases involving acute laryngitis and an associated risk of airway obstruction. Therefore, laryngoscopy becomes a necessary diagnostic tool , and the consideration of steroid administration and airway management should be based on symptoms that suggest a potential risk of airway obstruction in COVID-19 patients.5. References[1] Aur i s Nasus La rynx . 2023 Aug ; 50 (4 ) : 637–640.Published online 2022 Aug 23. doi: 10.1016/j.anl.2022.08.007[2] Jingyi Liang, Ruibin Liu, Wei He, et al . Infection rates of 70% of the population observed within 3 weeks after release of COVID-19 restrictions in Macao, China. J Infect. 2023 Jan 31[3] Wo r l d H e a l t h O r g a n i z a t i o n . C l i n i c a l
COVID-19 infection induced acute laryngitis or laryngitis caused by SARS-CoV-2/Omicron variant infection第 11 卷第 1 期 Volume 11 Número 1 Volume 11 Number 1 115management of COVID-19: interim guidance. 2020.[4] Front Immunol. 2020 Jun 16;11:1446. doi: 10.3389/fimmu.2020.01446. eCollection 2020.[5] QJM. 2021 Nov 5 ;114(7) :455-463 . do i : 10.1093/qjmed/hcab212.[6] Interim Infection Prevention and Control Recommendations for Healthcare Personnel D u r i n g t h e C o r o n a v i r u s D i s e a s e 2 0 1 9 (COVID-19) Pandemic. Updated Sept. 27, 2022
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The Macao Medical Journal (MMJ) (ISSN 1608-7801) is a comprehensive medical academic journal organized by the Health Bureau of the Macao SAR Government and published semi-annually in January and July by the Macao Academy of Medicine, with medical professionals as its main readers. All articles and manuscripts published in MMJ have been peer-reviewed to report on scientific research outcomes and clinical experience in the field of medical and health. The Journal is available for free access and is downloadable from the websites of the Health Bureau and the Macao Academy of Medicine to facilitate extensive academic exchange. 1. Categories of manuscripts The Journal publishes the following categories of manuscripts: Original clinical studies / researches, review articles / lectures and short articles / case reports.2. Guide for submission: (references from “Chinese Medical Journal”) 2.1. Manuscripts. The word count of submitted original clinical studies, discussion and review articles should generally be limited to 5000 (including legends of tables/graphs and references). Short articles and case reviews should not exceed 1500 words (including legends of tables/graphs and references). The process of submission will be entirely by electronic means. Authors are required to send their manuscript (in .doc or .docx format) by e-mail to mmj@ssm.gov.mo, with “Submission_Name of First Author_Manuscript Title” as the subject of the email. The cover letter/title page should contain the following information: Title of the manuscript, name(s) of all authors, name(s) of their department(s), their contact telephone number and email address; name of the corresponding author, type and no. of his/her identification document, name of his/her department, his/her telephone number and postal and email address.2.2. Language. To align with international standards and academic purposes, authors are encouraged to produce the full text in English; manuscripts presented in Chinese or Portuguese must have an English abstract (400 words). The abstract of an original article must consist of the following four parts: “Objective”, “Method”, “Results” and “Conclusions”, with each bearing their respective heading; these four parts are not required for abstracts of review articles and case reports. 2.3. Authorship. Authors’names should be written with the surname capitalized―for example, LIU ZhengQian or Zheng Qian LIU. The order of authorship should be settled prior to the submission of the manuscript, and should not be changed during the editorial process.2.4. Keywords. Each original article should have 2-5 English keywords, which should be selected as much as possible from the Medical Subject Headings (MeSH) database of the United States National Library of Medicine (NLM). Keywords should be separated by a semicolon (;). The first letter of each English keyword should be capitalized.2.5. Ethics approval. Manuscripts pertaining to research or work involving the use of human subjects must be accompanied by the approval of the regional/national/institutional ethics committee if deemed appropriate.2.6. Referencing. References should be cited according to the requirements of "Chinese Medical Journal" GB/T7714-2005 "Regulations for Bibliographic References" and GB 3469-1983 "Document Types and Document Carrier Codes". Articles with Digital Object Identifier (DOI) must list DOI at the end of the reference. Regarding the number of references, monographs, reviews, and lectures are generally limited to 20 or less, and 10 or less for short articles and case reviews. The following are examples of reference format: [1] Lam UP, Lopes Lao EP, Lam KC, Evora M, Wu Nq. Trans-brachial artery access for coronary artery procedures is feasible and safe: data from a single-center in Macau. Chin Med J 2019;132:1478-1481. doi: 10.1097/ CM9.0000000000000274. [ 2 ] 黎旭 , 刘兴鹏 , 刘⼩慧 , 等 . 早期他汀药物治疗与非缺血性扩张性心肌病患者病死 率关系的研究 [ J ] . 中华医学杂志,2010,90(28):1974-1977. doi: 10.3760/ cma.j.issn.0376-2491.2010.28.009.3. Declaration A declaration letter should be submitted together with the manuscript to express:3.1. The author(s)’s supervisor(s)/superior(s) is/are aware of the content of the manuscript;3.2. There is no issue on confidentiality;3.3. There is no issue on controversy about the name order of authors;3.4. The work has not been submitted to other journals;3.5. The manuscript is original work and not under consideration for publication elsewhere;3.6. The submission is approved by all authors.Macao Medical JournalGuide for Authors 2024
4. Instructions for Submission Authors are responsible for all material presented in the journal. If authors do not receive any feedback one month after receiving an acknowledgement of receipt, it means the manuscript is still under review. Authors should avoid multiple submissions to other journals, and should contact the Editorial Office if they wish to do so. Authors can write to appeal if the manuscript is rejected for publication. Accepted manuscripts may be edited or abridged by the Editorial Office prior to publication. Edited content involving change of the original idea would be referred to the authors for consideration. Authors who fail to return the corrected proof within 14 days will be regarded as having withdrawn the manuscript. The copyright to all published materials is owned by the Macao Medical Journal, whose copyright is owned by the Macao Academy of Medicine. 5. Contact of Editorial Office Postal address: Editorial Office of “Macao Medical Journal”, 5/F, Administration Building of the Health Bureau, Rua Nova à Guia no. 339, Macao.Tel.: (853)-8390 3253 / (853)-6252 0657E-mail: mmj@ssm.gov.mo
A“Revista Médica de Macau” (ISSN1608-7801) é uma revista académica de medicina abrangente, editada pelos Serviços de Saúde do Governo da RAEM e publicada oficialmente e semestralmente em Janeiro e Julho pela Academia Médica de Macau, tendo como principais leitores os profissionais da área de medicina. Todos os artigos publicados na Revista Médica de Macau foram revisados por pares para relatar os resultados da investigação científica e a experiência clínica no âmbito da medicina e da saúde. A Revista está disponível para acesso gratuito e pode ser descarregada na página electrónica dos Serviços de Saúde e da Academia Médica de Macau para facilitar o intercâmbio académico.1. Categorias dos artigos A Revista publica as seguintes categorias de artigos: Monografias e Estudos, Síntese e Palestras, Artigos Curtos e Relatórios de Casos.2. Requisitos para submissão (Vide “National Medical Journal of China”e“Chinese Medical Journal”) 2.1. Artigos. As monografias, sínteses, palestras, etc., geralmente não devem exceder 5 000 palavras (incluindo figuras, tabelas e documentos de referência); enquanto os artigos curtos, relatórios de casos clínicos, etc., não devem exceder 1 500 palavras (incluindo figuras, tabelas e documentos de referência). O processo de submissão é feito de forma electrónica, os autores devem enivar os seus artigos (em formato .doc ou .docx) por e-mail para mmj@ssm.gov.mo, com “Submissão_Nome do Primeiro Autor_Título do Artigo” como assunto do e-mail. A carta de apresentação/página de rosto deve conter as seguintes informações: título do artigo, nomes de todos os autores, nome(s) da(s) sua(s) unidade(s) de trabalho, número de telefone e endereço de e-mail; o nome, tipo e n.º do documento de identificação do autor responsável pela comunicação com a secção editorial, nome da instituição onde presta funções, endereço para correspondência, número de telefone e endereço de e-mail.2.2. Linguagem. Para satisfazer as necessidades académicas a nível internacional, propõe-se que o texto seja redigido em língua inglesa. Caso seja publicado em língua chinesa ou portuguesa, o resumo deve ser redigido em língua inglesa (400 palavras). O resumo de um artigo original deve ser composto pelas quatro partes: Objectivo, Método, Resultados e Conclusão, cada uma com os respectivos títulos. As sínteses e relatórios de casos clínicos não precisam incluir as quatro partes acima.2.3. Autor. Os sobrenomes dos autores, em línguas estrangeiras, devem ser escritos em letras maiúsculas, por exemplo: LIU ZhengQian ou Zheng Qian LIU. O nome do autor deve ser escrito sob o título, sendo a ordem determinada antes da submissão e não deve ser alterada durante o processo editorial.2.4. Palavras-chave. Devem ser indicadas 2 a 5 palavras-chave em inglês para a monografia. As palavras-chave devem ser seleccionadas no banco de dados de Medical Subject Headings (MeSH) da Biblioteca Nacional de Medicina dos Estados Unidos (The United States National Library of Medicine, NLM) tanto quanto possível, e ser separadas por ponto e vírgula (;). A primeira letra de cada palavra-chave em inglês deve ser maiúscula.2.5. Aprovação ética. Caso o conteúdo dos artigos envolva o uso de seres humanos como objecto de investigação, deve ser acompanhado dos pareceres de aprovação da Comissão de Ética (unidade, região ou país relacionado).2.6. Referências. As referências devem ser listadas de acordo com GB/T7714-2005 “Descriptive rules for bibliographic references”e GB 3469-1983 “Codes for documentary types and documentary carriers”, exigidos pelo “National Medical Journal of China” , e os artigos com Digital Object Identifier (DOI) devem identificar DOI no final de referência. Em relação ao número de referências das monografias, sínteses e palestras, é limitado a vinte ou menos. Para os artigos curtos e relatórios de casos, as referências são limitadas a dez ou menos. O seguinte formato é para referência: [1] Lam UP, Lopes Lao EP, Lam KC, Evora M, Wu Nq. Trans-brachial artery access for coronary artery procedures is feasible and safe: data from a single-center in Macau. Chin Med J 2019;132:1478-1481. doi: 10.1097/ CM9.0000000000000274. [ 2 ] 黎旭 , 刘兴鹏 , 刘⼩慧 , 等 . 早期他汀药物治疗与非缺血性扩张性心肌病患者病死 率关系的研究 [ J ] . 中华医学杂志,2010,90(28):1974-1977. doi: 10.3760/ cma.j.issn.0376-2491.2010.28.009.3. Carta de declaração. A carta de declaração deve ser enviada juntamente com o artigo, a qual deve incluir:3.1 Ter dado conhecimento prévio do conteúdo do artigo aos superiores hierárquicos do autor;3.2 O artigo não contém matéria confidencial;3.3 Não existe nenhuma contestação a respeito da ordem de apresentação dos nomes dos autores;3.4 O artigo não foi submetido a outras publicações periódicas;3.5 O artigo é um trabalho original e não está a ser ponderada a sua publicação noutro lugar;3.6 A submissão foi aprovada por todos os autores.Normas para Publicação na“Revista Médica de Macau”2024
4. Instruções para submissão Os autores são responsáveis por todos os artigos apresentados na presente revista. Se os autores não receberem nenhuma notificação do processamento do artigo dentro de um mês após o recebimento do recibo, isso significa que o artigo ainda está em revisão. Os autores devem evitar submissões múltiplas para outras publicações periódicas. Se desejarem submeter os artigos para outras publicações periódicas, os autores devem entrar em contacto a secção editorial. Para os artigos rejeitados, os autores podem apresentar opiniões de forma escrita para efeitos de impugnação. Além disso, os artigos aceitos podem ser editados ou abreviados pela secção editorial antes da publicação. Sempre que o conteúdo editado envolva a mudança da ideia original, é encaminhado aos autores para consideração. Se o artigo revisado não for devolvido no prazo de 14 dias, será considerado como desistência. Os direitos de autor de todos os artigos publicados pertencem a esta revista, cujos direitos de autores da “Revista de Ciências da Saúde de Macau” pertencem à Academia Médica de Macau.5. Contacto Endereço: Rua Nova à Guia, n.º 339, Edifício da Administração dos Serviços de Saúde, 5.º andar, secção editorial da “Revista Médica de Macau”.Tel: (853) 8390 3253 / (853) 6252 0657E-mail: mmj@ssm.gov.mo
