Iok Na MA et al. Volume 13 Número 1 Volume 13 Number 1 3A long-term (25 years) result and analysis of cervical cytological examination in MacaoAbstractObjective: To explore situation and significance of Macao's long-term (25 years) cervical cytological examination.Methods: Cervical cytology specimens were collected from the Pathology Department of Kiang Wu Hospital for 25 years (January 1998 to December 2022). All of subjects were divided into three age groups: less than or equal to 30 years old, 31 to 65 years old, and older than the 65-year-old group, the positivity rates of groups were analyzed. The diagnostic results, positivity rate and detection techniques were analyzed statistically.*Corresponding author: Kin Iong CHAN, E-mail: jammy_chan@hotmail.comDOI : 10.30224/MMJ.202601_13(1).0001Iok Na MA, Cho Sim CHAN, Fai WAN, Heong Teng WONG, Kin Iong CHAN*2525 1998 1 2022 123 30 31~65 65696736 64365 ThinPrep2000241952 BD SurePath™ 390419 30 119887 31~65 563533 6513316 5.46% 38053 ASC-US 3.67% 25597 ASC-H 0.20% 1363 LSIL 1.08% 7545 HSIL 0.32% 2203 SCC 0.003% 20 AGC 0.19% 1309 AIS 0.00043% 3 Ad.Ca 0.001% 13 ASC-US/SIL=2.63 4.31% 2776ThinPrep2000 5.12% 12397 BD SurePath™ 5.86%22880 P<0.001 306.13% 7348 31~65 5.27% 29700 65 7.55% 1005P<0.001BD SurePath™65TBS
25Revista Médica de Macau Macao Medical Journal4Results: A total of 696736 cervical cytology examination specimens including 64365 traditional Pap smear specimens, 241952 ThinPrep2000 liquid-based cytology specimens and 390419 BD SurePath™ liquid-based cytology specimens were collected. There were 119887 specimens in the 30-year-old and younger group, 563533 cases in 31 to 65-year-old group, and 13316 cases in the age group over 65 years old. The total positive rate was 5.46% (38053 cases), in which, ASC-US 3.67% (25597 cases), ASC-H 0.20% (1363 cases), LSIL 1.08% (7545 cases), HSIL 0.32% (2203 cases), SCC 0.003% (20 cases), AGC 0.19% (1309 cases), AIS 0.00043% (3 cases), and Ad.Ca 0.001% (13 cases). ASC-US/SIL=2.63. The positive rate of traditional Pap smears was 4.31% (2776 cases), the positive rate of ThinPrep2000 liquid-based cytology was 5.12% (12397 cases), and the positive rate of BD SurePath™ liquid-based cytology was 5.86% (22880 cases). The difference of positive rates between 3 detection techniques was very significant statistically (P<0.001). The positive rate was 6.13%(7348 cases) in the 30-year-old and younger group, 5.27%(29700 cases) in 31-65 group, and 7.55%(1005 cases) in over 65 years old group. The difference of positive rates between 3 groups of age was very significant in statistically (P<0.001).Conclusion: The long-term cervical cytological examination results in this study reliably reflect the cervical cytological examination status of women in Macao. BD SurePath™ liquid-based cytology is the most sensitive cervical cytology positive detection technique. Since the positive detection rate in the group over 65 years old remains high, therefore, patients in this age group also need to be concerned.Keywords: Cervical cancer; Cervical cytological examination; TBS system20202020 60.430.2 [1]1940George PapanicolaouThinPrep2000 BD SurePath™19851998-20221. 1.1 1998-2022696736 151887544849 114-951.2ThinPrep2000 BD SurePath™TBS The Bethesda System, TBSNegative for Intraepithelial Lesion or Malignancy, NILMAtypical Squamous Cells of Undetermined Significance, ASC-USAtypical Squamous
25 Volume 13 Número 1 Volume 13 Number 1 5Cells of Undetermined Significance-cannot rule out High-grade lesion, ASC-HLow-grade squamous intraepithelial lesion, LSIL High-grade squamous intraepithelial lesion, HSILSquamous cell carcinoma, SCCAtypical glandular cells, AGCAdenocarcinoma in situ, AISAdenocarcinoma, Ad.Ca ASC-USASC-US/SIL331~65 >651.3 SPSS 25.02 P<0.052. 696736 380535.46% ASC-US 25597 3.67%A S C - H 1 3 6 3 0 . 2 0 % L S I L 7 5 4 51.08% HSIL 2203 0.32% SCC 200.003% AGC 1309 0.19% AIS 30.00043% Ad.Ca 13 0.001% 1ASC-US/SIL=25597/9748=2.631 1998 2022
25 Volume 13 Número 1 Volume 13 Number 1 94. [1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Sta t is t ics 2020: GLOBOCAN Estimates of Incidence and Mortal i ty Wo r l d w i d e f o r 3 6 C a n c e r s i n 1 8 5 Countries. Ca Cancer J Clin 2021,71:209-249. doi: 10.3322/caac.21660.[2] Davey DD, Naryshkin S, Nielsen ML, et al. Atypical squamous cells of undetermined significance: interlaboratory comparison and quality assurance monitors. Diagn Cytopathol 1994,11(4) :390-396. doi : 10.1002/dc.2840110416.[3] Nascimento AF, Cibas ES. The AC/SIL ratio for cytopathologists as a control measure: a follow-up study. Am J Clin Pathol 2007,128(4):653-656. doi: 10.1309/APTVNLP1P0X00CUQ.[4] Cibas ES , Zou KH, Crum CP, e t a l . Using the rate of positive high-risk HPV test resul ts for ASCUS together with the ASCUS/SIL ratio in evaluating the performance of cytopathologists. Am J Clin Pathol 2008,129(1):97-101. doi : 10.1309/KXV1MA3L9HMQU7HY.[5] , , g .1 1 2 0 8 0 B e t h e s d a. , 2019,25(7):489-493. doi:10.16406/j.pmt.issn.1672-9153.2019.07.004[6] Honarvar Z, Zarisfi Z, Sedigh SS, et al. Comparison of conventional and liquid-based Pap smear methods in the diagnosis of precancerous cervical lesions. J Obstet Gynaec 2022 ,42 (6 ) :2320-2324 . do i : 10.1080/01443615.2022.2049721.[7] Jeong H, Hong SR, Chae SW, e t a l . Comparison of unsatisfactory samples from conventional smear versus liquid-b a s e d c y t o l o g y i n u t e r i n e c e r v i c a l cancer screening test . J Pathol Transl Med 2017,51(3):314-319. doi: 10.4132/jptm.2017.03.17.[8] , , . 3 3 4 1 7 . , 2012,9(23): 2947-2948. doi:10.3969/j.issn.1672-9455.2012.23.017[9] Wang Y, Li L, Douville C, et al. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med 2018 Mar 21:10(433):eaap8793. doi:10.1126/scitranslmed.aap8793.[10] , , . 2 4 2 4 8H P V. , 2022,12(30):2798-2801. doi :10.3969/j.issn.1004-8189.2022.12.027[11] , , . 2020[J]. , 2020,36(12): 1177-1183. doi: 10.19538/j.fk2020120113.
Hong Tou CHAN et al.Revista Médica de Macau Macao Medical Journal101. IntroductionTuberculosis (TB) is a communicable disease that ranks among the leading causes of mortality worldwide, surpassing HIV/AIDS as the most lethal infectious agent. TB is caused by Mycobacterium tuberculos i s and i s t ransmi t ted v ia a i rborne particles expelled by infected individuals. While approximately one-quarter of the global population is infected with TB, only a fraction will develop active disease.In 2022, an estimated 10.6 million people developed TB, resulting in 1.3 million deaths. Globally, TB remains the second leading infectious killer after COVID-19[1]. The WHO introduced the End TB Strategy in 2014, which aims to achieve a 90% reduction in TB mortality and an 80% decrease in incidence by 2030. By 2025, TB-related deaths should be reduced by 75%, and no patient should experience catastrophic healthcare costs due to TB.CTB is the primary institution responsible for TB prevention, treatment, and public health The strategy and challenges of tuberculosis control and prevention in MacaoAbstractTuberculosis (TB) remains one of the deadliest infectious diseases globally, posing a threat to both developing and developed regions. In 2014, the World Health Organization (WHO) proposed the End TB Strategy, targeting a 90% reduction in TB incidence and a 95% reduction in TB deaths by 2035. Macao Special Administrative Region (Macao SAR, Macau) has demonstrated a steady decline in TB incidence, from 105.7 per 100,000 population in 2001 to 46.2 per 100,000 in 2023, reflecting a total decrease of 58%. Despite this progress, Macao has not yet met the WHO 2025 milestone target, which requires a 50% reduction in TB incidence to 28.8 per 100,000 population. This is a retrospective review of tuberculosis control and prevention in Macao. Epidemiological data from the Tuberculosis Prevention and Treatment Centre CTB) Surveillance Information System (TB SIS) indicate that TB incidence is increasing among the elderly, individuals with diabetes mellitus (TB-DM comorbidity), and non-residents. In response, CTB has implemented proactive screening programs in high-risk settings, such as nursing homes and among individuals aged 65 and above with diabetes. Additionally, Macao has introduced conditional exemptions for medical fees for non-residents to enhance TB treatment accessibility. This review aims to raise awareness among healthcare professionals and the public regarding TB control efforts in Macao.Keywords: Tuberculosis; Pulmonary; Prevention and Control; End TB Strategy1Department of Pneumology, Conde de Sao Januario General Hospital, Macao China.2Department of Centro de Prevencao e Tratamento de Tuberculose, Macao China.*Corresponding author: Hong Tou CHAN, E-mail: Chanhtpneum@yahoo.com.hkDOI : 10.30224/MMJ.202601_13(1).0002Hong Tou CHAN1,2*, Tak Hong CHEONG1, Kouk Hei CHOU2, Meng Wai CHAN2, Lai In TOU2, Ka In U2, Tin Hou MOK1
The strategy and challenges of tuberculosis control and prevention in Macao Volume 13 Número 1 Volume 13 Number 1 11screening in Macao. It follows WHO guidelines, inc luding ac t ive and pass ive case detec t ion , rapid molecular diagnostics, effective anti-TB treatment, directly observed therapy (DOT), TB preventive therapy (TPT) for latent TB infection (LTBI), neonatal Bacille Calmette-Guerin (BCG) vaccination, and continuous medical education for healthcare professionals and the public [2][3].However, Macao is a densely populated region with an aging demographic, a high prevalence of TB risk factors (e.g., smoking, diabetes, and alcohol use), and substantial migration from high-TB-burden regions. These factors present ongoing challenges for TB control efforts.2. MethodsAccording to Administrative Regulation No. 15/2008 of Macao, TB is classified as a second-ca tegory compulsory no t i f i ab le d i sease . Al l suspected or confirmed TB cases are managed at CTB. The data analyzed in this respect ive review were obtained from CTB's TB Surveillance Information System (TB SIS), which senior public health and statistics professionals maintain by WHO standards. The database includes epidemiological trends, clinical outcomes, and treatment efficacy, which are reported annually to WHO for global surveillance.3. Results CTB in Macao has ach ieved no tab le advancements in tuberculosis (TB) control, with a 58% decline in incidence rates documented since 2001. Nevertheless, persistent challenges remain, particularly in individuals aged 65 and non-resident demographic groups (refers to non-resident workers, non-resident students, holding visit permits and prisoners). This retrospective review examines key insights into epidemiological patterns, therapeutic outcomes, and the efficacy of implemented intervention strategies. The principal findings are summarized as follows (Table 1):3.1 General TB Epidemiology in Macao over the past decadeThe number of new TB cases has declined from 393 in 2014 to 315 in 2023,representing a 19.8% reduction.P u l m o n a r y T B ( P T B ) a c c o u n t s f o r approximately 85% of cases, while extrapulmonary TB accounts for 15%.Due to the increased utilization of molecular diagnostics (e.g., GeneXpert MTB/RIF Ultra), the bacteriological confirmation rate for PTB has risen from 82.4% in 2014 to 90.3% in 2023.TB incidence remains higher among males (65%) than females (35%).TB-DM cases have increased from 12.4% of total TB cases in 2013 to 24.4% in 2023 (Figure 1).TB-HIV co-infection remains low, with fewer than five cases annually.TB-related mortality ranges from 23 to 38 deaths per year, predominantly affecting individuals over 65 years old (>65%).3.2 Effectiveness of TB Control StrategiesThe TB incidence rate has steadily declined by 58% since 2001, reaching 46.2 per 100,000 population in 2023. It was similar to that in the Great Bay Area city with 40 and 43 per 100,000 population in Guangdong Province and Hong Kong respectively. Macao has been defined as a lower-moderate TB incidence region since 2022 (Figure 2). Treatment success rates exceed 90% for drug-susceptible TB and 80% for drug-resistant TB, surpassing WHO global averages.The TB treatment success rate among older people remains above the WHO benchmark of 85%.Drug-resistant TB cases remain low, with fewer than 10 new cases annually (~2%of total cases).
The strategy and challenges of tuberculosis control and prevention in MacaoRevista Médica de Macau Macao Medical Journal12Table 1. Epidemiological indicators of tuberculosis (2014–2023) derived from the CTBTuberculosis Surveillance Information System.2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Total TB case 393 372 358 381 328 363 365 340 299 315TB incidence rate / 100,000 61.8 57.5 55.5 58.3 49.1 53.4 53.4 49.8 44.4 46.1 Pulmonary TB case (PTB) / %329 (84%)324 (87%)299 (84%)325(85%)279 (85%)320 (88%)284 (78%)281 (83%)259 (87%)278 (88%)Extra-Pulmonary TB case / %64 (16%)48 (13%)59 (16%)56 (15%)49 (15%)43 (12%)81 (22%)59 (17%)40 (13%)37 (12%)Pulmonary TB bacteriological(+) rate % 82.4% 81.8% 82.3% 86.2% 85.7% 83.4% 88.7% 86.8% 88.0% 90.3%SexMale % 66.2% 69.1% 64.0% 65.6% 65.5% 65.0% 64.1% 69.1% 59.2% 72.4%Female % 33.8% 30.9% 36.0% 34.4% 34.5% 35.0% 35.9% 30.9% 40.8% 27.6% 65y TB % 16.3% 24.2% 27.7% 30.4% 26.5% 27.8% 30.7% 38.2% 35.5% 45.7%Non-resident TB % 12.0% 16.1% 10.6% 12.1% 15.2% 12.4% 15.1% 15.6% 17.1% 13.3%Multi-drug resistance/Rifampicin resistanceTB % 2.0% 2.7% 0.6% 0.3% 2.1% 1.9% 1.1% 1.8% 2.3% 2.2%Pre-X drug resistance/X drug resistance TB % 0.0% 0.5% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.3% 0.6%TB-Human Immunodeficiency Virus (+) case6 1 4 0 3 1 2 4 2 3TB-Diabetes Mellitus % 13.5% 15.1% 15.4% 15.0% 17.4% 17.9% 19.7% 19.7% 21.1% 24.4%TB Death ( treatment outcome )* 27 26 32 38 23 32 37 38 30TB Death ( die from TB ) 0 1 9 9 6 3 9 5 16 7Treatment success rate 96.3% 95.8% 97.1% 93.7% 94.1% 95.6% 94.4% 93.2% 94.1%65y treatment success rate 88.0% 92.2% 86.7% 82.8% 88.1% 86.4% 85.9% 80.9% 82.4%Drug Resistance TB treatment success rate 66.7% 80.0% 100.0% 100.0% 66.7% 80.0% 75.0% 60.0% 75.0%Notes:*TB Death (treatment outcome): death from any cause during the period of TB treatment.TB Death (die from TB): died directly from TB.Not available due to: from May to June every year, the WHO will collect last year's TB data from regions and member countries, as well as TB treatment-related outcome data from two years ago, because a considerable part of the treatment spans two years.
The strategy and challenges of tuberculosis control and prevention in Macao Volume 13 Número 1 Volume 13 Number 1 13Figure 1. Demonstrates an inverse directional relationship: the red trendline (TB notification rate/100,000 population) exhibits a declining trajectory. In contrast, the blue trendline (proportion of TB-DM comorbidity among annual incident TB cases) shows a concurrent upward trend, indicating divergent epidemiological dynamics over the study period.Figure 2. The results represent the Tuberculosis (TB) new cases and the notification rates from 2001 to 2023; both numbers are steadily declining.4. DiscussionDespite significant progress, Macao faces challenges in achieving the WHO 2025 milestone target for TB incidence reduction. Several factors contribute to this challenge:4.1 Aging PopulationThe proportion of individuals aged 65 years old or above increased from 14.1% in 2020 to a projected 21.4% by 2029.Elderly TB cases have risen from 18.4% of total cases in 2013 to 45% in 2023.4.2 TB-Diabetes Comorbidity T B - D M p a t i e n t s h a v e h i g h e r r a t e s o f bacteriological positivity, prolonged treatment durat ion, and increased drug resistance. I t is associated with a two- to threefold increased risk of developing active TB, a twofold higher mortality rate during TB treatment, a fourfold greater likelihood of TB relapse post-treatment, and a twofold elevated risk of multidrug-resistant TB (MDR-TB).A 5-year da ta [2] rev iew reveals TB-DM patients, compared to TB without DM, demonstrate (49.9% vs. 25%), elevated bacteriological positivity (19.5% vs. 11.9%), sustained sputum smear positivity post-2-month treatment (19.5% vs 11.9%), and increased any drug resistance (15.8% vs 11.8%).DM is a high-risk factor for TB. The co-occurrence of the two diseases leads to double burden and mutual influence. Local Statistics shows the prevalence of DM increased from 5.3% in 2006
The strategy and challenges of tuberculosis control and prevention in MacaoRevista Médica de Macau Macao Medical Journal14to 7.1% in 2016[4]. The increasing prevalence of DM not only increases the risk of TB, but also poses the challenges to the treatment and management of TB.4.3 Non-Resident TB CasesThe proportion of TB cases among non-local residents has grown from 2.5% in 2002 to 13.3% in 2023.The age distribution is mainly concentrated between 25 to 44 years old, most cases originate from high-TB-burden neighboring regions. Among the non-resident cases, workers accounted for 81%, followed by students, holding visit permits and prisoners.Macao s economy relies on tourism and gaming, which has led to a significant increase in foreign workers, the high mobility of foreign popu la t i on i nc r ea se s t he complex i t y o f TB transmission and management.4.4 Key StrategiesIf no robust health policies, social support, or new vaccines and drugs were introduced, and if the current 4% annual decline in TB incidence were maintained, TB incidence could be expected to fall to 34.5 per 100,000 by 2035 substantially lower than the WHO target of 10 per 100,000. To advance the goal of ending TB, CTB will continue its initiatives with the following key strategies:4.4.1 Sustain High Treatment Success: Ensure continued excellence in TB treatment outcomes and recovery rates.4.4.2 Enhance Active TB Screening [4] [5] Focus on high-risk populations, particularly individuals aged 65 and older and those with diabetes mellitus. Implement a biennial screening program in 39 nursing homes (covering over 5200 elderly residents and staffs). Conduct a pilot TB screening program for diabetic individuals aged 65 years or above at Fai Chi Kei Health Centre. [6] [7]4.4.3 Financial Support for Non-Resident CasesProvide conditional exemptions for medical fees, including LTBI treatment, follow-up, and medical observation for non-resident TB cases.4.4.4 Maintain Low Drug-Resistant TB Rates [8,9,10] Continue efforts to keep DR-TB rates stable and low. Introduce the new 6-month all-oral BPaLM regimen ( bedaquiline, pretomanid, l inezolid, and moxif loxacin) which showed s ignif icant improvement cure rates, enhancement treatment completion, and reduction adverse events compared to the standard 18–24-month regimen. Since Oct 2024, six patients have been using this treatment regimen, the main concern is on peripheral nervous symptoms which are mild and manageable, the overall side effects are fewer than older regimens, the patient s tolerance and compliance are high. The biggest highlight of this regimen is that the treatment course is shortened from 18 months to 6 months. Although this treatment regimen is very expensive, given the low annual case numbers (<10 cases), this regimen will have minimal impact on medical resources.4.4.5 Adopt Advanced Molecular DiagnosticsExpand the use of rapid automated molecular tests and AI-assisted radiographic imaging to boost detection rates in hospital and health center settings.4.4.6 Expand LTBI Screening and Preventive Treatment [11,12]Increase LTBI screening coverage among high-risk groups using the forthcoming ESAT6/CFP10 (EC-Test), a cost-effective skin test with comparable specificity and sensitivity to IGRAs, with minimal logistical requirements.4.4.7 Broaden DOT ImplementationExtend the directly observed therapy (DOT) strategy beyond governmental health centers to include private corporate clinics.5. ConclusionMacao should continue to strengthen health policies and social support to reduce TB incidence and meet WHO End TB targets. Key measures include sustaining high treatment success rates, expanding ac t ive TB screening among high-risk groups (e.g., elderly and TB-DM patients), and offering fee exemptions for non-residents to
The strategy and challenges of tuberculosis control and prevention in Macao Volume 13 Número 1 Volume 13 Number 1 15ensure adherence. Wider adoption of molecular d iagnos t i c s , inc reased LTBI sc reen ing wi th preventive therapy, and introduction of shorter regimens (e.g., BPaLM) for drug-resistant TB are also critical. By aligning interventions with local epidemiological trends, Macao can make significant progress toward ending TB.6. Reference[1] World Health Organization. (2023). Global Tuberculosis Report 2023 (ISBN 978-92-4-008385-1). WHO.[2] Center for Tuberculosis, Macao. (2023). Macao Tuberculosis Annual Report 2023.[3] C h i n e s e C e n t e r f o r D i s e a s e C o n t r o l and Prevention. (2021, June). Technical guidelines for tuberculosis prevention and control in China.[4] Macao Health Bureau. (2016). Macao health surveillance 2016.[5] Cheng, J., & Zhao, Y. (2024). Strategies for active screening in tuberculosis-free community construction. Chinese Journal of Antituberculosis, 46(6), 605-612.https://doi.org/10.19982/j.issn.1000-6621.20230435[6] Zhu, L. (2024). Reflections on improving t u b e r c u l o s i s s c r e e n i n g p o l i c i e s f o r d i a b e t i c p a t i e n t s i n C h i n a . C h i n e s e J o u r n a l o f A n t i t u b e r c u l o s i s , 4 6 ( 3 ) , 2 6 7 - 2 7 1 . h t t p s : / / d o i . o r g / 1 0 . 1 9 9 8 2 /j.issn.1000-6621.20230436[7] Macao Health Bureau. (2016). Macao health surveillance 2016.[8] WHO guidelines & operational handbook: Module 4:Drug-resistantTB treatment 2022[9] Update o f d rug- res i s tan t tubercu los i s t r ea tment gu ide l ines : A tu rn ing po in t International Journal of Infectious Disease Volume 130, Supplement 1, May 2023, Pages S12-S15 https://doi.org/10.1016/j.ijid.2023.03.013[10] World Health Organization. (2024). Current WHO recommendations on the treatment of drug-resistant TB: Update on the Guideline Development Group meeting 2024.[11] Rapid communication: TB antigen-based skin tests for the diagnosis of TB infection World Health Organization 2022 WHO/UCN/TB/2022.1[12] To, K. W., Zhang, R., & Lee, S. S. (2024). Is the new tuberculous antigen-based skin test ready for use as an alternative to tuberculin skin test/interferon-gamma release assay for tuberculosis diagnosis? A narrative review. International Journal of Infectious Diseases, 141(Suppl.), 106992. https://doi.org/10.1016/j.ijid.2024.106992
Sin Mui CHAO et al.Revista Médica de Macau Macao Medical Journal16The impact of gestational diabetes mellitus on pregnancy outcomes in MacaoAbstractObjective: This Macau-based study examined pregnancy outcomes by comparing women with and without gestational diabetes mellitus (GDM) through analysis of abnormal glucose metabolism during pregnancy. Methods: The differences in pregnancy outcomes between 1,070 women with GDM and those without GDM were analyzed using the Cohort study. The case group consisted of 535 Chinese women diagnosed with GDM who gave birth at the Conde de São Januário General Hospital in Macao, while the control group comprised an equal number of Chinese women without GDM who gave birth during the same period. A 1:1 simple random sampling method was used, excluding GDM, impaired glucose tolerance (IGT), and pre-pregnancy diabetes (DM). Blood glucose levels were monitored postpartum for 741 women diagnosed with GDM. Results: The cesarean section rates and assisted delivery rates for GDM pregnant women with singleton and twin pregnancies, as well as the singleton preterm birth rates and the incidence of gestational hypertension, are all higher than those in the control group, with statistically significant differences (P<0.05). Among the 741 women with GDM, 301 underwent postpartum glucose screening, including fasting blood glucose or HbA1C. Of these, 114 underwent a 75g oral glucose tolerance test (OGTT), which revealed that 11 women *Corresponding author: Sin Mui CHAO, E-mail: catherinestephen1999@gmail.comDOI : 10.30224/MMJ.202601_13(1).0003Sin Mui CHAO*(GDM) GDM1 070 GDM GDMGDM 535 GDM1:1 GDM IGT DM 535GDM 741GDMP <0.05 GDM 741HbA1C 301 301 OGTT 75g 114 2 119.6% IGT 52 45.6% IFG 3 2.6% IFG IGT 10 8.8%GDM 2 T2DM GDM
Volume 13 Número 1 Volume 13 Number 1 17(9.6%) had type 2 diabetes, 52 women (45.6%) had IGT, 3 women (2.6%) had impaired fasting glucose, and 10 women (8.8%) had both impaired fasting glucose and IGT. Conclusion: GDM pregnant women have poorer pregnancy outcomes, with an increased risk of developing type 2 diabetes in the future. It is essential to enhance monitoring and management of GDM to reduce its negative impact on maternal and neonatal health.Keywords: Gestational diabetes mellitus; Pregnancy outcomesGestational Diabetes Mellitus, GDM(International Association of Diabetes in Pregnancy Study Group, IADPSG) GDMGDM14.0%[1] GDM21%[2] 2006 2007GDM 6.2% 7.5%[3]2008 2010 9 296GDM8.64% 7.58% 7.75%[4][5]GDM2 Type 2 Diabetes Mellitus, T2DM [6]1. 1.1 2008-20101 070GDM 535 GDM 1:1GDM IGT Diabetes Mellitus, DM 535 GDM 7411.2 GDM 24 2850 g Glucose Challenge Test, GCT l hOral Glucose Tolerance, OGTTGDM[7-8] 28OGTT 100gAmerican Diabetes Association ADA [7]L 1 h 2 hmmol/L 3 hGDM GDM [7] 6 12 OGTT 75g 3.60 5.83 mmol/L 2 3.90 6.70 mmol/L GDM:75g 2 hGlycated Hemoglobin HbA1CT2DM 2h 6.7111.0mmol/L Impaired Glucose Tolerance IGT 5.84 mmol/L6.99mmol/L Impaired Fasting Glucose IFG 2 h1.3 ApgarHbA1COGTT 75g 2 h1.4 SPSS 17.0 [ (%)] 2
Volume 13 Número 1 Volume 13 Number 1 213. GDM2=12.16 P 0.01 2=4.63 P0.05 2=7.10 P 0.05( Apgar ) 2 =4.78P 0.05 2=10.93 P0.01 GDM[9-11]GDM T2DMT2DM 9.6%IGT 45.6% GDMGDM T2DMGDM 10 GDM50%~60% [12]T2DM50%[13]6 T2DM 28T2DM 70%[14]t=8.08 P=0.00GDM22=2.41 P 0.053 BMIrs=–0.196 P=0.00 BMIP=0.242GDM 12008-2010 GDMGDMGDM GDMGDMGDMGDMGDMT2DMGDM4. [1] Wang H, Li N, Chivese T, Werfall i M, Sun H, Yuen L, Hoegfeldt CA, Elise Powe C, Immanuel J, Karuranga S, Divakar H, Levitt N, Li C, Simmons D, Yang X; IDF Diabetes Atlas Committee Hyperglycaemia in Pregnancy Special Interest Group. IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Preva lence fo r 2021 by In te rna t iona l Associa t ion of Diabetes in Pregnancy Study Group's Criteria. Diabetes Res Clin Pract, 2022, 183: 109050. DOI:10.1016/j.diabres.2021.109050.[2] Zhu H, Zhao Z, Xu J, Chen Y, Zhu Q, Zhou L, Cai J, Ji L. The prevalence of g e s t a t i o n a l d i a b e t e s m e l l i t u s b e f o r e a n d a f t e r t h e i m p l e m e n t a t i o n o f t h e
Revista Médica de Macau Macao Medical Journal22universal two-child policy in China. Front Endocrinol (Lausanne), 2022, 13: 960877. DOI:10.3389/fendo.2022.960877.[3] . . 2012 [C]. : [ ], 2012.[4] . [D]. , 2013.[5] , . [ J ] . , 2021 , 36(1) : 27-29 . DOI :10 .19829/ j . zgfyb j . i s sn .1001-4411.2021.01.010.[6] , . 2m e t a [ J ] . , 2 0 2 0 , 2 3 ( 7 ) : 4 5 9 . D O I : 1 0 . 3 7 6 0 / c m a .j.issn.1007-9408.2020.07.102.[7] American Diabetes Association Professional Practice Committee. Summary of Revisions: S tandards of Care in Diabetes 2024. Diabetes Care, 2024, 47 (Supplement_1): S5–S10. DOI:10.2337/dc24-SREV.[8] R a n i P R , B e g u m J . S c r e e n i n g a n d Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand. J Clin Diagn Res, 2 0 1 6 , 1 0 ( 4 ) : Q E 0 1 - 4 . D O I : 1 0 . 7 8 6 0 /JCDR/2016/17588.7689.[9] , . [J]. , 2024, 31(20): 73-77. DOI:10.3969/j.issn.1674-4721.2024.20.019.[10] Li J, Yan J, Ma L, Huang Y, Zhu M, Jiang W. Effect of gestational diabetes mellitus on pregnancy outcomes among younger and older women and its additive interaction w i t h a d v a n c e d m a t e r n a l a g e . F r o n t Endocrinol (Lausanne), 2023, 14: 1158969. DOI:10.3389/fendo.2023.1158969.[11] Ye W, Luo C, Huang J, Li C, Liu Z, Liu F, et al. Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis. BMJ, 2022, 377: e067946. DOI:10.1136/bmj-2021-067946.[12] , . 2 0 2 2[J]. , 2022, 25(4): 313-315. DOI:10.3760/cma.j.cn113903-20220125-00079.[13] Chowdhury S, Hasan T, Mir MI. Gestational D i a b e t e s M e l l i t u s . K YA M C J o u r n a l , 2018, 9(2): 81-86. DOI:10.3329/kyamcj.v9i2.38154.[14] Kim C, Newton KM, Knopp RH. Gestational d i abe te s and the inc idence o f t ype 2 diabetes: a systematic review. Diabetes Care, 2002, 25(10): 1862-8. DOI:10.2337/diacare.25.10.1862.
Pek San HO et al. Volume 13 Número 1 Volume 13 Number 1 23Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysisAbstractObjectives: To assess the prevalence and identify factors associated with the development of diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM) in a primary care setting.Design: A community-based cross-sectional study.Subjects: The study included all newly diagnosed and known T2DM patients who attended diabetic retinopathy screening appointments at the Ilha Verde Health Center from June 1, 2020, to December 31, 2020.Main Outcome Measures: The prevalence of DR among patients with T2DM and the identification of associated risk factors for its development.Results: Of the 3,062 diabetic patients who underwent retinal photography, 252 (8.23%) had positive findings. The majority had mild non-proliferative diabetic retinopathy (NPDR) (n=179, 71.03%), followed by moderate NPDR (n=56, 22.22%), severe NPDR (n=9, 3.57%), and clinically significant macular edema (CSME) (n=8, 3.17%). Higher HbA1c levels, longer duration of diabetes, and the presence of proteinuria were significantly associated with increased DR risk.Conclusion: The prevalence of DR in this study was lower than the global average. Statistically significant risk factors were identified, underscoring the importance of early screening and intervention to prevent DR progression in high-risk patients.Keywords: Diabetic retinopathy (DR); Retinal photography; Risk factors; Community-based studyCentro de Saúde da Ilha Verde*Corresponding author: Pek San HO, E-mail: daphne_san99@yahoo.com.hkDOI : 10.30224/MMJ.202601_13(1).0004Pek San HO*, Mei Kun LOK, Chong Po CHOI1. IntroductionDiabetes mellitus (DM) is becoming a significant public health challenge in the Asia-Pacific region, with type 2 diabetes mellitus (T2DM) being the most prevalent form among adults in Macau. According to the 2016 Macau Health Survey, the prevalence of diabetes in the adult population is 7.1%. Chronic hyperglycemia in diabetes is associated with various long-term complications, which can be broadly categorized into cardiovascular and microvascular diseases, including retinopathy, nephropathy, and neuropathy.[1]Diabetic retinopathy (DR) remains one of the leading preventable causes of visual impairment and blindness in the working-age population.[2] Visual loss in DR can result from complications such as macular edema, preretinal or vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma. [3]Since early-stage DR is often asymptomatic, early identification and intervention are critical to reducing the risk of vis ion impairment . Several r isk factors have consistently been l inked to DR development,
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysisRevista Médica de Macau Macao Medical Journal24including male gender, obesity, prolonged diabetes du ra t ion , e l eva ted g lycohemoglob in l eve l s , hypertension, hyperlipidemia, pregnancy, and diabetic nephropathy.[4-7]G l o b a l l y, a p p r o x i m a t e l y o n e - t h i r d o f individuals with diabetes develop some form of DR, although prevalence varies across populations. A 2012 meta-analysis by Yau et al. estimated the overall global prevalence of DR at 34.6%.[8] More recently, the International Diabetes Federation (IDF) Diabetes Atlas reported a global prevalence of 27.0% for DR from 2015 to 2019, comprising 25 .2% non-p ro l i f e r a t i ve DR (NPDR) , 1 .4% proliferative DR (PDR), and 4.6% diabetic macular edema (DME). Regional variations were noted, with the lowest prevalence in Europe (20.6%) and Southeast Asia (12.5%) and the highest in Africa (33.8%), the Middle East and North Africa (33.8%), and the Western Pacific (36.2%).[9]Studies from China reported a DR prevalence of 34.1% and 27.9% among predominantly T2DM patients, with mild NPDR accounting for 15.8% and 22.1%, PDR for 0.89% and 2.1%, and DME for 11.5% and 11.2%.[10,11] In Hong Kong, a local screening program found a DR prevalence of 39.0%, mainly mild NPDR, with 0.3% PDR and 8.6% DME.[12]The American Diabetes Association (ADA) recommends that patients with T2DM undergo an initial comprehensive dilated eye examination by an ophthalmologist or optometrist at the time of diagnosis.[13] DR screening has been available in Macau s primary care health centers since 2001. Currently, two health centers provide DR screening, bu t i nc reas ing pa t i en t numbers and l imi t ed resources have led to long waiting times. Given the high prevalence of DM and the importance of early DR detection, prioritizing screening for high-risk patients could facilitate timely diagnosis and management, thereby improving outcomes for this population.2. Methods2.1 Study DesignThis study was a cross-sectional analysis conducted at the Ilha Verde Health Center, located in one of Macau s districts. According to Health Bureau statistics, the two health centers responsible for diabetic fundus examinations served a total of 9,144 patients in 2020. All patients with type 2 diabetes who were invited to participate in diabetic retinopathy (DR) screening between June 1, 2020, and December 31, 2020, were included. The patient list was retrieved from the Hospital Information System in January 2023.A p o s i t i v e f i n d i n g w a s d e f i n e d a s t h e presence of any degree of DR detected via fundus photography, while a negative finding was defined as the absence of retinopathy. Fundus photographs were taken using the TOPCON TRC-NW400 non-mydriatic automated retinal camera, operated by trained nurses. Two 45-degrees fields (one macula centred and one optic disc centred) digital, colour fundal photographs of each eye were taken. The images were graded by a trained family physician using IMAGEnet 6 software. The severi ty of DR was classified according to the International Clinical Diabetic Retinopathy (ICDR) and Diabetic Macular Edema Disease Severity Scales, which categorize DR into five stages and classify macular edema as either absent or present.[14] This study was approved by the Hospital Medical Ethical Committee.2.2 Data CollectionData were collected by reviewing the hospital informat ion sys tem, which included medical consultat ion notes, diabetic ret inopathy (DR) screening reports, and blood test results. Diabetes diagnoses were made by medical practitioners based on the 2011 ADA criteria.[15] All patients with diabetes, except for children under 12 years of age, were eligible for inclusion. Patients with a diabetes duration of less than one year were classified as newly diagnosed. The duration of diabetes was
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysis Volume 13 Número 1 Volume 13 Number 1 25calculated as the time interval between the date of diagnosis and the date of fundus examination.The collected variables included age, gender, diabetes duration, and history of hypertension. Additional data recorded included smoking status, body mass index (BMI), glycated hemoglobin A1c (HbA1c) levels, lipid profile (LDL-cholesterol), presence of proteinuria (categorized as none, microalbuminuria, or macroalbuminuria), and estimated glomerular filtration rate (eGFR). The presence and severity of DR, including any grading and/or maculopathy, were also documented.Diabetic nephropathy was defined by the presence of microalbuminuria or macroalbuminuria. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. Chronic kidney disease stages were classified according to the National Kidney Foundation (NKF) guidelines as follows: Stage 1 (evidence of kidney damage), Stage 2 (eGFR 60–89 ), Stage 3 ( ), Stage 4 ( ), and Stage 5 (eGFR ).[16]All data were systematically recorded in a data collection spreadsheet for subsequent analysis.2.3 Sample Size CalculationAs there was no reported prevalence of DR among local diabetic patients in Macau, prevalence data from surveys conducted in China and Hong Kong were used for reference, which indicated a prevalence range of 27.9% to 39% among diabetic patients.[10-12] Based on these findings, a midpoint prevalence of 33% was selected for the sample size calculation. Assuming a population proportion of 0.33, the minimum sample size required to achieve an absolute precision of 5% with a 95% confidence level was calculated to be 340 participants.2.4 OutcomesThe primary objective of this study was to determine the prevalence of diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM) in a primary care setting in Macau. The secondary objective was to identify the factors associated with the development of DR.2.5 Statistical AnalysisData analysis was conducted using SPSS vers ion 22.0 . Propor t ions were presented by percentages, while continuous variables with a normal distribution were reported as means with standard deviations. Univariate analysis for categorical variables was performed using the Chi-square test, and for continuous variables, the independent sample t-test was applied. Multivariate analysis was conducted using logistic regression to identify significant predictors of DR. A p -value of <0.05 was considered statistically significant.3. Results3.1 Study PopulationA total of 3,566 patients with T2DM were included in this study. The clinical characteristics of the participants are detailed in Table 1. The mean age of the cohort was 64 years, with 50.5% of the patients being male. Additionally, 70.7% of the participants were classified as either overweight or obese, and the prevalence of diabetic nephropathy was 22.8%.A l l e l i g i b l e p a t i e n t s w e r e i n v i t e d t o participate, and all provided consent to undergo fundus photography. However, 504 individuals (14.1%) were unable to complete the examination, primarily due to factors such as absence, dense cataracts, small pupils, or inability to follow the nurse's instructions. Consequently, the final study population comprised 3,062 patients.
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysisRevista Médica de Macau Macao Medical Journal26Table 1. Demographic data and clinical characteristics of patients N=3566 .Number (%) Mean (SD)Age (years) 64.47 (9.84)<40y 48 (1.35)40–50y 171 (4.80)50–60y 798 (22.38)60–70y 1518 (42.57)70–80y 802 (22.49)>=80y 229 (6.42)GenderMale 1803 (50.56)Female 1763 (49.44)Duration of Diabetes (years) 6.91 (4.98)<1y 311 (8.72)1~6y 1219 (34.18)7~14y 1394 (39.09)>=15y 138 (3.87)Missing 504 (14.13)Current smokerYes 146 (4.09)No 3420 (95.91)History of HypertensionYes 2162 (60.63)No 1404 (39.37)Body mass index (kg/m²) 25.47 (3.82)<23 890 (24.96)23~25 765 (21.45)>=25 1758 (49.30)Missing 153 (4.29)HbA1c (%) 7.40 (1.28)<7 1533 (42.99)7~8 1156 (32.42)>=8 873 (24.48)Missing 4 (0.11)LDL-cholesterol (mmol/L) 2.44 (0.84)<1.8 786 (22.04)1.8~2.6 1397 (39.18)>=2.6 1381 (38.73)Missing 2 (0.06)Proteinuria 48.69 (253.64)<20 2688 (75.38)continued
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysis Volume 13 Número 1 Volume 13 Number 1 273.2 Prevalence of Diabetic RetinopathyThe prevalence of diabetic retinopathy (DR) is summarized in Table 2. In this study, 8.2% of the participants had positive findings. Among newly diagnosed diabetes cases, 19 patients (6.11%) had DR, compared to 233 patients (8.47%) with previously known diabetes.In total, 252 patients (8.23%) had positive findings. The majority had mild non-proliferative diabetic retinopathy (NPDR) (n=179, 71.03%), followed by moderate NPDR (n=56, 22.22%), severe NPDR (n=9, 3.57%), and clinically significant macular edema (CSME) (n=8, 3.17%). No cases of proliferative DR were observed (Table 3).Table 2. Prevalence of diabetic retinopathy among different patient groupsN=3062 .Table 3. Severity of screening result N=252 .20~200 660 (18.51)>=200 154 (4.32)Missing 64 (1.79)Estimated glomerular filtration rate (ml/min/1.73 m²) 83.74 (22.63)<30 38 (1.07)30~60 419 (11.75)>=60 3107 (87.13)Missing 2 (0.06)
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysisRevista Médica de Macau Macao Medical Journal283.3 Associated factors for diabetic retinopathyTo identify risk factors associated with the development of DR, various clinical parameters were analyzed across the diabetic patient cohort. A total of 2,962 patients were included in the data analysis, with 100 cases excluded due to missing data, as outlined in Table 1. The analysis presented in Table 4 revealed that HbA1c levels, duration of diabetes, and the presence of proteinuria were significantly associated with DR, while other parameters showed no statistically significant c o r r e l a t i o n . F u r t h e r m o r e , m u l t i p l e l o g i s t i c regression analysis also revealed that higher HbA1c, prolonged diabetes duration, and proteinuria were strong predictors of DR (Table 5).Table 4. Risk factor profile for all DM patient N=2962 .Table 5. Multiple logistics regression analysis of predictor of DR N=2962 .
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysis Volume 13 Número 1 Volume 13 Number 1 294. Discussionepidemiological investigation of diabetic retinopathy (DR) prevalence in Macau. The prevalence rate of 8.23% observed in our cohort is notably lower than the previously reported range of 27–39% in neighboring regions, as well as lower than the prevalence rates reported in Europe and other Asia-[9-12] However, prevalence estimates varied considerably across studies, depending on the population and study methodology. The published studies involved populations exclusively with type 1 or type 2 diabetes or a mixture of both. Some studies were based on community populations, while others focused on hospital populations. Such differences in prevalence may stem from a combination of diabetes type, genetic factors, different ethnicities, healthcare accessibility, and varying methodologies for DR screening and reporting. Socioeconomic factors, including urbanization, poverty, malnutrition, and inadequate healthcare access, likely contribute to the higher prevalence of DR in low- and middle-income countries and may also explain some disparities in rates and severity of DR among different ethnic groups. This highlights the considerable difficulties in deriving a truly meaningful global prevalence rate for DR at this time.A u n i q u e a s p e c t o f o u r s t u d y i s t h a t i t p redominant ly inc luded pa t ien ts wi th s tab le glycemic control, as those with poorly managed diabetes were often referred to specialists for further evaluation. Among our participants, 42.99% achieved an HbA1c level below 7%, with a mean HbA1c of 7.4% (SD 1.28%). Additionally, 61.22% had LDL-cholesterol levels below 2.6 mmol/L, and 75.38% showed no signs of diabetic nephropathy.Our findings provide valuable epidemiological insights into the risk factors associated with DR. Consistent with prior research, we found that longer diabetes duration is a significant risk factor for DR, with more than 60% of diabetic patients expected to develop some degree of DR after 20 years.[17-19] In our study, a diabetes duration of 15 years emerged as a critical threshold for DR risk. Furthermore, elevated HbA1c levels showed a positive correlation with DR, reinforcing the role of poor glycemic control as a major contributor. The association between proteinuria and DR observed in our cohort aligns with the understanding that both are microvascular complications of diabetes.Most cases with positive finding in our study were classified as mild non-proliferative diabetic retinopathy (NPDR), highlighting the potential for early detection. Based on these findings, we recommend regular DR screening for all patients w i th t ype 2 d i abe t e s . I den t i fy ing h igh - r i sk individuals based on key predictors such as HbA1c levels, diabetes duration, and proteinuria can enable earlier intervention, potentially preventing the progression to vision-threatening stages. In addition, aggressive management of modifiable risk factors could substantially reduce the burden of DR in this population.5. LimitationsWe acknowledge several limitations in our study. First, the participants were recruited from a single health center in a specific district, and the recruitment interval was short, which may limit the generalizability of the findings to the broader population of Macau. Second, the sample size for certain subgroups with specific associated factors was relatively small, potentially leading to an underestimation of their significance in the development of diabetic retinopathy. Third, the precise onset of diabetic retinopathy in patients wi th newly d iagnosed d iabetes could not be accurately determined, which may have affected our understanding of the early progression of the condition. Finally, variations in screening methods and diagnostic criteria could introduce potential biases, impacting the comparability of our results with other studies.
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysisRevista Médica de Macau Macao Medical Journal306. ConclusionIn conclusion, this study provides preliminary insights into the prevalence and risk factors of diabetic retinopathy (DR) in patients with type 2 d iabe tes mel l i tus in Macau . The observed prevalence of DR was lower than reported in other regions, highlighting potential differences in population characteristics and healthcare systems. The Macau Health Centers provide primary health care services by region; offer all residents easy access and free services. Statistically significant associations were identified between key risk factors such as elevated HbA1c levels, longer d iabe tes dura t ion , and p ro te inur ia and the development of DR. These findings underscore the importance of prioritizing early screening for high-risk individuals to enable timely intervention. Moving forward, targeted risk factor management based on patient profiles could play a crucial role in preventing the progression of DR and reducing its burden on the healthcare system.7. References[1] MODEL, Chron ic Care . S tandards o f medical care in diabetes 2015 abridged fo r p r imary ca re p rov ide r s . D iabe te s Care, 2015, 38.1: S1-S94. doi: 10.2337/diaclin.33.2.97.[2] S T E I N M E T Z , J a i m i e D . C a u s e s o f blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study (vol 2, pg 144, 2021). LANCET GLOBAL HEALTH, 2021, 9.4: E408-E408. doi:10.1016/S2214-109X(20)30489-7.[3] F O N G , D o n a l d S . , e t a l . D i a b e t i c r e t i n o p a t h y . D i a b e t e s C a r e . 2 0 0 3 Jan:26 Suppl 1:S99-S102. doi: 10.2337/diacare.26.2007.s99.[4] SONG, Ki Ho, et al. Discordance in risk factors for the progression of diabetic retinopathy and diabetic nephropathy in patients with type 2 diabetes mell i tus. Journal of diabetes investigation, 2019, 10.3: 745-752. doi: 10.1111/jdi.12953.[5] CHEW, Emily Y., et al . The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control C a r d i o v a s c u l a r R i s k i n D i a b e t e s (ACCORD) Eye Study. Ophthalmology, 2014, 121.12: 2443-2451. doi:10.1016/j.ophtha.2014.07.019[6] GROUP, UK Prospective Diabetes Study. Tight b lood pressure contro l and r i sk o f m a c r o v a s c u l a r a n d m i c r o v a s c u l a r complications in type 2 diabetes: UKPDS 38. BMJ: British Medical Journal, 1998, 703-713. doi:10.1136/bmj.317.7160.703.[7] K O B R I N K L E I N , B a r b a r a E d e n . O v e r v i e w o f e p i d e m i o l o g i c s t u d i e s o f d i a b e t i c r e t i n o p a t h y. O p h t h a l m i c epidemiology, 2007, 14.4: 179-183. doi: 10.1080/09286580701396720.[8] YAU, Joanne WY, et al. Global prevalence a n d m a j o r r i s k f a c t o r s o f d i a b e t i c retinopathy. Diabetes care, 2012, 35.3: 556-564. doi: 10.2337/dc11-1909.[9] THOMAS, R. L . , e t a l . IDF Diabe tes Atlas: A review of studies utilising retinal photography on the global prevalence of diabetes related retinopathy between 2015 and 2018. Diabetes research and clinical practice, 2019, 157: 107840. doi: 10.1016/j.diabres.2019.107840.[10] LIU, Yan, et al . Prevalence of diabetic retinopathy among 13473 patients with diabetes mellitus in China: a cross-sectional epidemiological survey in six provinces. B M J o p e n , 2 0 1 7 , 7 . 1 : e 0 1 3 1 9 9 . d o i : 10.1136/bmjopen-2016-013199.[11] ZHANG, Guihua, et al. Prevalence and risk
Diabetic retinopathy screening in primary care clinics in Macau: A community-based cross-sectional analysis Volume 13 Número 1 Volume 13 Number 1 31factors for diabetic retinopathy in China: a mul t i -hospi ta l -based cross-sect ional study. British Journal of Ophthalmology, 2017, 101.12: 1591-1595. doi: 10.1136/bjophthalmol-2017-310316.[12] LIAN, Jin Xiao, et al. Systematic screening for diabetic retinopathy (DR) in Hong Kong: prevalence of DR and visual impairment among diabetic population. British Journal of Ophthalmology, 2016, 100.2: 151-155. doi: 10.1136/bjophthalmol-2015-307382.[13] American Diabetes Association Professional Prac t ice Commit tee : 12 . Ret inopathy, neuropathy, and foot care: standards of medical care in diabetes 2022. Diabetes Care 2022;45(Supplement_1):S185–S194. doi: 10.2337/dc22-S012.[14] Wilkinson, Charles P. , e t a l . Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity sca les . October 2003; Ophthalmology 1 1 0 ( 9 ) : 1 6 7 7 . D O I : 1 0 . 1 0 1 6 / S 0 1 6 1 -6420(03)00475-5.[15] A m e r i c a n D i a b e t e s A s s o c i a t i o n ; Standards of Medical Care in Diabetes2011. Diabetes Care 1 January 2011; 34 (Supplement_1): S11–S61. doi: 10.2337/dc11-S011.[16] AS, LEVEY. National Kidney Foundation. Na t iona l Kidney Founda t ion p rac t i ce guidel ines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med., 2003, 139: 137-147. doi: 10.7326/0003-4819-139-2-200307150-00013.[17] BALLARD, D. J., et al. Risk factors for diabetic retinopathy: a population-based study in Rochester, Minnesota. Diabetes care, 1986, 9.4: 334-342. doi: 10.2337/diacare.9.4.334.[18] MCKAY, Robert; MCCARTY, Catherine A.; TAYLOR, Hugh R. Diabetic retinopathy in Victoria, Australia: the visual impairment project. British journal of ophthalmology, 2 0 0 0 , 8 4 . 8 : 8 6 5 - 8 7 0 . d o i : 1 0 . 11 3 6 /bjo.84.8.865.[19] American Diabetes Association. Position statements: diabetic retinopathy. Diabetes Care 2003;26(suppl 1): S99-S102. doi: 10.2337/diacare.26.2007.s99.
32Prevalence of chronic kidney disease among diabetic patients in Macao's primary healthcare12*Corresponding author: Nelson TJIE, E-mail: nelsonmx@hotmail.com DOI : 10.30224/MMJ.202601_13(1).0005Nelson TJIE1*, In Wong2202258.9% CKDp<0.05ACEI/ARB SGLT2CKD[1, 2]2022 2AbstractObjectives: To analyze the prevalence of chronic kidney disease among diabetic patients in Macau. Method: A cross-sectional observational study was conducted, retrospectively analyzing diabetic patients who visited Macau health centers in 2022. Results 58.9% of diabetic patients had chronic kidney disease, with age, gender, and blood glucose control status influencing the prevalence. Discussion: This study highlights the need to improve diabetes and kidney disease management. It suggests optimizing medication use to address poor blood pressure and blood glucose control, thereby enhancing patients' renal and cardiovascular health.Keywords: Diabetes; Chronic kidney disease; Prevalence
Revista Médica de Macau Macao Medical Journal406. [1] American Diabetes Association Professional Practice, C. (2022). 11. Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes-2022. Diabetes Care, 45(Suppl 1), S175-S184. doi:10.2337/dc22-S011[2] de Boer, I. H., Khunti, K., Sadusky, T., Tuttle, K. R., Bakris, G. (2022). Diabetes Management in Chronic Kidney Disease: A Consensus Repor t by the Amer ican Diabetes Association (ADA) and Kidney Disease : Improving Global Outcomes (KDIGO). Diabetes Care, 45(12), 3075-3090. doi:10.2337/dci22-0027[3] de Boer, I . H., Rue, T. C., Hall, Y. N., Weiss, N. S., & Himmelfarb, J. (2011). Tempora l t rends in the preva lence of diabetic kidney disease in the United States. JAMA, 305(24), 2532-2539. doi:10.1001/jama.2011.861[4] Dena, M., Svensson, A. M., Olofsson, K. E., Young, L., Carlson, A., Miller, K., Lind, M. (2021). Renal Complications and Duration of Diabetes: An International Comparison in Persons with Type 1 Diabetes. Diabetes Ther, 12(12), 3093-3105. doi:10.1007/s13300-021-01169-w[5] Guo, K., Zhang, L., Zhao, F., Lu, J., Pan, P. (2016). Prevalence of chronic kidney disease and associated factors in Chinese individuals with type 2 diabetes: Cross-sectional study. J Diabetes Complications, 3 0 ( 5 ) , 8 0 3 - 8 1 0 . d o i : 1 0 . 1 0 1 6 /j.jdiacomp.2016.03.020[6] Hallstrom, S., Pivodic, A., Rosengren, A., Svensson, A. M., & Lind, M. (2019). Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry. Diabetes Care, 42(8), 1530-1538. doi:10.2337/dc18-2457[7] Hil l , C . , Cardwel l , C . , Pa t te r son , C . , M a x w e l l , A . , M a g e e , G . , Yo u n g , R . , Fogarty, D. J. D. M. (2014). Chronic kidney disease and diabetes in the national health service: a cross sectional survey of the UK national diabetes audit. 31(4), 448-454. doi:10.1111/dme.12312[8] 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 Diabe tes Work , G . (2022) . KDIGO 2022 Clinical Practice Guideline fo r Diabe tes Management in Chron ic Kidney Disease. Kidney Int, 102(5S), S1-S127. doi:10.1016/j.kint.2022.06.008[9] Levey, Andrew S . , Rudy B i lous , and Michael G. Shlipak. "CKD and diabetes: what can we learn from their similarities and differences?." American Journal of Kidney Diseases 67.3 (2016): 360-363. doi:10.1053/j.ajkd.2015.12.003[10] Levey, A. S. , Stevens , L. A. , Schmid, C. H., Zhang, Y. L., Castro, A. F., 3rd, Feldman, H. I., Ckd, E. P. I. (2009). A new equation to estimate glomerular filtration rate. Ann Intern Med, 150(9), 604-612. doi:10.7326/0003-4819-150-9-200905050-00006[11] McKenney, J. M. (2003). Update on the National Cholesterol Education Program Adul t Treatment Panel I I I guidel ines : getting to goal. Pharmacotherapy, 23(9 Pt 2), 26S-33S. doi:10.1592/phco.23.11.26s.32710[12] Mok, K. Y., Chan, P. F., Lai, L. K. P., Chow, K. L., & Chao, D. V. K. (2019). Prevalence of diabetic nephropathy among Chinese patients with type 2 diabetes mellitus and different categories of their est imated glomerular f i l trat ion rate based on the Chronic Kidney Disease Epidemiology Col labora t ion (CKD-EPI) equat ion in p r imary ca re in Hong Kong: a c ross -sectional study. J Diabetes Metab Disord,
Volume 13 Número 1 Volume 13 Number 1 4118(2), 281-288. doi:10.1007/s40200-018-00382-y[13] Parv ing , H . H . , Lewi s , J . B . , Rav id , M., Remuzzi , G. , Hunsicker, L. G. , & investigators, D. (2006). Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int, 69(11), 2057-2063. doi:10.1038/sj.ki.5000377[14] Russo, G.T., De Cosmo, S., Viazzi, F. et al. Diabetic kidney disease in the elderly: prevalence and clinical correlates. BMC Geriatr 18, 38 (2018). doi:10.1186/s12877-018-0732-4[15] Whelton, P, Carey, R, Aronow, W. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. JACC. 2018 May, 71 (19) e127–e248. doi:10.1016/j.jacc.2017.11.006[16] Wong, I. (2019). Study of type 2 diabetes management among patients in a Macau primary care setting. Fam Med Community Health, 7(3), e000031. doi:10.1136/fmch-2018-000031[17] Yacoub, R., & Campbell, K. N. (2015). Inhibition of RAS in diabetic nephropathy. I n t e r n a t i o n a l J o u r n a l o f N e p h r o l o g y and Renovascu la r Disease , 8 , 29–40 . doi:10.2147/IJNRD.S37893[18] Yang, L., Chu, T. K., Lian, J., Lo, C. W., Nan, H., & Liang, J. (2018). Risk factors of chronic kidney diseases in Chinese adults with type 2 diabetes. Sci Rep, 8(1), 14686. doi:10.1038/s41598-018-32983-1
Zhao Man HE et al.Revista Médica de Macau Macao Medical Journal42The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysisAbstractObjectives: To analyse the medical burden generated by hospital admissions related to adverse drug reactions (ADRs) at a hospital in Macau. Methods: Data were collected on non-elective admissions of adult patients from 1 April 2023 to 30 September 2023 (a total of 6 months). Admissions related to ADRs were compared to non-ADR-related admissions to assess the impact of ADRs on hospitalisation costs and length of stay. Results: Among the admissions, 151 patients (3.1%) were admitted due to ADRs, and 77 patients (1.6%) had incidental ADRs at admission, the latter group had a longer length of stay compared those without ADRs (median: 13 vs. 7 days, p < 0.001) and a 1.8-fold increase in total hospitalisation costs (468.6 points vs. 249.6 points, p < 0.001). Diagnostic costs accounted for the highest proportion of costs in ADR-induced admission. The most common reason for ADR-induced admission was bleeding/abnormal INR, which was associated with significantly higher hospitalisation costs compared to other ADR events. Conclusion: ADR-related admissions impose a substantial medical burden. Strengthening ADR prevention and monitoring is an important measure to mitigate this issue.Keywords: Adverse drug reactions; Hospitalisation rate; Cost; AvoidabilityPharmacy Department, Kiang Wu Hospital, Macau*Corresponding author: Zhao Man HE, E-mail: hermanh0228@gmail.comDOI : 10.30224/MMJ.202601_13(1).0006Zhao Man HE*, Sio Han CHEONG, Tek Fai CHAN, Sai In IEONG, Ka Kit CHAN1. IntroductionADRs contr ibute to increased morbidi ty, hospitalisation rates, and healthcare costs [1], making them a critical concern for healthcare systems. ADRs not only affect healthcare effectiveness but also elevate the financial burden on healthcare systems. Studies report wide variability in ADR-related hospitalisation rates, ranging from 0.2% to 41.3% [2–5]. Although a local hospital study found a relatively low prevalence of ADR-related admissions (4.6%) [6], the associated economic impact remains unclear. Studies suggest that many countries allocate 15% to 20% of their hospital budgets to ADR-related treatments [7]. A meta-analysis suggests that the cost per ADR-related admission ranges from 422 USD to 7,062 USD [5], while another study focusing on elderly patients found that ADRs prolong hospital stays by an average of 5.6 days, further increasing medical and medication expenses [8].H o w e v e r, r e s e a r c h o n t h e c o s t - r e l a t e d implications of ADRs in Macau remains limited. This study aims to investigate the medical burden and cos t components associa ted wi th ADRs, providing a reference for fu ture research on healthcare costs related to ADRs in the local region.
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysis Volume 13 Número 1 Volume 13 Number 1 432. Patients and Methods2.1 Study populationWe col lec ted c l in ica l da ta on inpa t ien ts admitted to the hospital between 1 April 2023 to 30 September 2023 using the hospital information system.2.2 Inclusion and exclusion criteria:Inclusion criteria: Patients aged 18 years old and above; Non-elective admissions.Exclusion criteria: Hospital stay for less than 24 hours; Transferred from other hospitals; Admissions to the Obstetrics Department;Admissions to the Palliative Care Department; Not discharged during the study period; Substance abuse or intentional poisoning; ADRs due to complementary and alternative medicine (CAM). 2.3 ADRs evaluation: The assessment of whether patients experienced ADRs was conduc t ed by t h r ee i ndependen t clinical pharmacists. This evaluation was based o n p a t i e n t s m e d i c a l r e c o r d s , m e d i c a t i o n orders , and supplementary informat ion f rom UpToDate, Micromedex, and summaries of product characteristics (SmPCs). The study utilised the Liverpool Causality Assessment Tool (LCAT) to evaluate the causality of each suspected ADR. Only cases classified as "def in i te" or "probable" according to the LCAT were included in the statistical analysis [9]. Additionally, the Hallas scale was used to assess the preventability of identified ADRs [10].2.4 Assessment of medical burden: Medical expenditures and length of hospital stay were extracted from the hospital information system, which records all costs incurred during hospitalisation. These included medical care and nursing costs, medication costs, treatment costs, diagnostic costs, surgical costs, accommodation costs, and other miscellaneous costs. Costs were analysed according to the admission types (ADR-induced admission, incidental ADR at admission and non-ADR-related admission), with comparisons made between different ADR events and their associated expenditures. As the s tudy was conducted in a pr ivate heal thcare faci l i ty, a l l monetary values were converted to a point-based system to standardise medical cost representation to avoids revealing confidential financial information. 2.5 Statistical methods: Statistical analyses were performed using SPSS version 26. Descriptive statistics were used to present the primary results. Categorical variables were expressed as percentages, while continuous variables were reported as medians with 95% confidence intervals (CIs). The Wilcoxon signed-rank tes t was employed to compare outcome di fferences . A two- ta i led p-va lue <0.05 was considered statistically significant.3. Results3.1 General characteristics of the study populationFrom 1 April 2023 to 30 September 2023, the hospital admitted a total of 16,099 patients. After applying the inclusion/exclusion criteria, 4,918 patients were included in this study (median age: 67 years; IQR: 52–79 years). Of these, 151 (3.1%) were ADR-induced admissions, while 77 (1.6%) were incidental ADRs at admission.3.2 Length of hospital stayThe median length of hospital stay differed signif icantly among the three groups: 8 days (95% CI: 7-9) for ADR-induced admissions, 13 days (95% CI: 10-16) for patients with incidental ADRs at admission, and 7 days (95% CI: 6-7) for non-ADR-related admissions. Patients with incidental ADRs at admission had significantly longer hospital stays than those without ADRs (z = 6.486, p < 0.001).3.3 Type of costs during hospitalisationMedical care and nursing costs accounted for approximately 25% of total expenditures in both the ADR-induced admission and admission with incidental ADR groups, representing the largest cost component in the latter. In contrast, diagnostic
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysisRevista Médica de Macau Macao Medical Journal44costs constituted the highest proportion of expenses for ADR-induced admissions, while surgical costs predominated in non-ADR-related admissions (Figure 1).Figure 1. Distribution of medical cost categories across three hospitalisation groupsAn analysis was conducted to compare the costs of ADR-induced admission and admission wi th inc iden ta l ADR wi th the cos t s o f non-ADR-rela ted admiss ions . The to ta l cos ts for pa t i en t s wi th inc iden ta l ADRs a t admiss ion were significantly higher than those for non-ADR-related admissions (z = 5.191, p < 0.001). Medica l ca re and nurs ing cos t s , medica t ion cos ts , t rea tment cos ts , d iagnost ic cos ts , and accommodation costs were significantly higher in the incidental ADR group compared to non-ADR-related admissions (all p < 0.05). However, no significant cost differences were observed between ADR-induced admissions and non-ADR-related admissions overall (p = 0.488), except for surgical costs, which showed a significant difference (p < 0.05). Medical care and nursing in the ADR- induced admiss ion g roup had a higher point (median = 50.5) compared to non-ADR-related group (median = 41.8), with a trend toward statistical significance (p = 0.053). The effect size, a median difference of 8.7 units (1.21-fold higher in ADR-induced admission group) suggests a potent ia l ly meaningful di fference despite the borderline p -value. (Table 1).
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysis Volume 13 Número 1 Volume 13 Number 1 45Table 1. Comparison of hospitalisation costs between ADR-related admissions (ADR-induced admission and admissions with incidental ADR) and non-ADRs-related admissions.Types of costsCosts for non-ADRs-related admissionsCosts for ADR-induced admissions Costs for admissions with incidental ADRMedian (95%CI) Median (95%CI) p-value Median (95%CI) p-valueTotal costs 249.6 (240.8-261.8)255.5 (182.5-303.7) 0.488 468.6 (364.3-640.1) <0.001Medical care and nursing costs 41.8 (39.8-43.4) 50.5 (45.8-62.2) 0.053 125.2 (81.0-166.5) <0.001Medication costs 28.2 (26.9-29.4) 30.6 (23.5-40.6) 0.373 63.0 (45.4-83.3) <0.001Treatment costs 7.5 (6.3-8.6) 4.5 (2.1-6.9) 0.166 27.8 (15.4-49.4) 0.001Diagnostic costs 82.9 (80.1-86.1) 79.7 (69.5-100.1) 0.660 129.1 (117.5-153.7) <0.001Surgical costs 197.6 (177.6-213.5) 66.0 (38.9-323.2) 0.023 303.2 (131.6-1186.8) 0.139Accommodation costs 30.0 (28.9-31.0) 33.0 (26.2-41.4) 0.504 93.1 (80.2-117.4) <0.001Other costs 0.6 (0.5-0.8) 0.6 (0.5-1.5) 0.985 0 (0-0.5) 0.086Medical care and nursing costs include consultation fees, nursing fees, monitoring fees and intensive care charges; Treatment costs include treatment fees and materials fees; diagnostic costs include testing fees and examination fees; accommodation costs include hospitalisation fees and meal fees during hospitalisation; other costs include additional disc burning fees and handling fees#Surgical costs only includes patients who actually incurred these costs for research calculation.3.4 Relationship between types of ADRs and costs during hospitalisation We observed that hospitalisation costs related to admissions due to bleeding/INR abnormalities were significantly higher when compared to admissions unrelated to such ADRs ( p < 0.05). In contrast, admissions unrelated to hypoglycaemia or other ( p < 0.05) in the ADR-induced admission group.Costs for admissions without incidental ADRs of ar rhythmia/bradycardia and bleeding/INR abnormalities were significantly higher (p < 0.05). Although not statistically significant (p = 0.053), admissions with incidental ADR of hypoglycaemia cos t 2 .07- fo ld more than those unre la ted to hypoglycaemia (median = 934.3 vs. 451.7 points; mean difference = 482.6 points) (Table 2).
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysisRevista Médica de Macau Macao Medical Journal46Table 2. Analysis of costs of admissions due to ADRs and the presence of ADRs at the time of admission across different types of ADR events.Types of ADRsCosts for ADR-induced admissionsCosts for admissions with incidental ADRNO. Median (Yes/No) p-value NO. Median (Yes/No) p-valueArrhythmia/Bradycardia 13 350.5/251.3 0.208 5 134.7/496.1 0.005Bleeding/INR abnormalities 53 301.4/193.9 0.004 19 307.7/531.0 0.021Peripheral edema 5 274.3/251.3 0.492 1 461.9/471.5 0.653Hypoglycemia 10 110.3/266.4 0.006 8 934.3/451.7 0.053Hypotension 7 165.2/256.9 0.426 3 890.4/465.2 0.292Liver/Renal dysfunction 5 216.7/256.9 0.512 11 729.4/460.9 0.415Gastrointestinal distress 13 220.3/257.0 0.507 0 N/A N/AMyelosuppression 7 238.3/257.0 0.804 0 N/A N/AInfection 6 283.9/255.5 0.879 0 N/A N/ADiabetic ketoacidosis 7 355.5/239.0 0.124 3 901.0/464.2 0.197Electrolyte disturbance 14 165.0/266.2 0.149 18 476.3/461.9 0.838Dizziness/Headache 4 250.0/255.5 0.945 1 354.1/471.5 0.928Others 7 91.7/263.0 0.006 8 577.1/461.9 0.278Others include interstitial lung disease, dysautonomia, endocrine dyscrasia, thyroid dysfunction, allergic reaction.Yes = ADR present, No = ADR absent.4. DiscussionADRs represent a significant public health concern, leading to patient harm, preventable hospitalisations, prolonged hospital stays, increased healthcare costs, and unnecessary healthcare system burdens. Our study population had a median age of 67 years, reflecting Macau's aging demographic trend [6,11]. This aligns with the average age reported in a Singaporean ADR study [3]. The observed ADR-induced admission rate of 3.1% was lower than the global benchmark of 5-10% [4], likely due to methodological differences, population characteristics, or regional variations in prescribing patterns.In this retrospective analysis, we found that the length of hospital stays for ADR-induced admission is similar to that of non-ADR-related admissions. Conversely, admissions with incidental ADRs had a longer hospital stay compared to non-ADR-related admissions, with approximately additional 6 days, which is consistent with previous studies conducted abroad [12-14]. The main reason may be that ADR-induced admissions have a clearer cause for hospitalisation, with diagnoses that are relatively straightforward and distinct, hence less time is needed for making diagnosis and developing an appropriate treatment plan. In most ADR-related cases, the primary treatment is to discontinue the
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysis Volume 13 Número 1 Volume 13 Number 1 47suspected drugs as soon as possible and outcome can usually be seen in a short time, resulting in a shorter length of hospital stay. Yet, admissions with incidental ADRs often involve more challenges associated with diagnosis and treatment. In addition to treating the primary condition, there is a need for additional treatment for ADRs, and some symptoms of ADRs are similar to those of underlying diseases, further increasing the complexity of treatment. A longer length of stay, medical care and nursing care are dervived as a result in this group of patient. Among the t o t a l co s t s o f ADR- induced admission group, the highest proportion is attributed to diagnostic fees. This is primarily because, in this study, bleeding/INR abnormalities are the most common ADRs leading to hospitalisation, management often involves frequent blood tests to detect signs of blood loss, clotting issues and organ damage, as well as medical imaging examinations, including ultrasound scans, X-rays, and computed tomography (CT) scans, to identify the site and extent of bleeding episodes . These tes ts and examinations accounted for at least 30% of the total hospitalisation costs in 54% of patients admitted fo r b leed ing / INR abnormal i t i e s . Our s tudy also reveals that ADR-induced admissions and admissions with incidental ADR are primarily drug-related, with medical treatment being predominant, there is relatively little involvement of surgical interventions.In con t ras t , admiss ions a s soc ia t ed wi th incidental ADRs cost more in most cost categories, except surgical costs and miscellaneous expenses, compared to non-ADR-related admissions, with a significant difference in total cost, reaching over 1.8 times higher due to the complexity of management, as noted earlier. However, the total cost for ADR-induced admissions remains similar to that of non-ADR-related admissions. This finding is consistent with studies conducted abroad [3, 14, 15] and aligns with the observed length of hospital stays in this study. Although the difference between medical care and nursing costs of ADR-induced admissions and non-ADR-related admissions did not reach statistical significance, the observed effect size, a median difference of 8.7 points, suggests a cl inical ly meaningful t rend, which needed to confirm these findings in the future work with larger samples.The findings reveal a distinct contrast in cost patterns between ADR-induced admissions and those with incidental ADRs. For ADR-induced admissions, the significantly higher median cost assoc ia ted wi th b leed ing / INR abnormal i t i es aligns with expectations, as these cases typically associated with more severe clinical scenarios, such as cerebral hemorrhage or gastrointestinal bleeding, requir ing intensive management . In contrast , incidental bleeding/INR abnormalities usually involves less severe bleeding incidents, such as gingival hemorrhage or mild INR increase, and they were often identified through routine monitoring. Less intensive management and early detection result in comparatively lower treatment costs. Furthermore, the costs of managing an ADR such as hypoglycaemia were significantly lower because of its less intensive treatment and monitoring requirements.Combining the result of our previous studies, approximately 95% of admissions due to ADRs are classified as definitely or possibly avoidable [6], which could free up as many as 1,147 bed days and reduce the medical burden by about 36,351.5 points for patients, leading to substantial savings for both patient s families and the entire healthcare system.This study has several limitations. As a single-centre study, the findings may not be broadly generalisable to other healthcare facil i t ies in Macau. The retrospective design relied entirely on electronic medical records from physicians, nurses, and other healthcare professionals, which introduces inherent limitations in data completeness and accuracy. Additionally, our study only assessed in-hospital costs and did not account for post-discharge outcomes such as readmissions or long-
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysisRevista Médica de Macau Macao Medical Journal48term complications. Future studies should address these limitations through multi-centre designs and extended follow-up periods.In conclusion, the costs and length of stay for admissions with incidental ADR are both significantly higher than ADR-induced admissions and non-ADR-related admissions, and the costs for admissions due to bleeding/INR abnormalities are significantly greater than those for other types of ADRs. In the future, early identification and prevention of ADRs will be important measures to reduce the burden on patients and the entire healthcare system [16]. Pharmacists can play a crucial role in the identification and prevention of ADRs by intervening with patients on high-risk medications, as well as involving in the medical management of high-risk populations such as geriatric patients or patients with polypharmacy. This can be achieved by providing effective consultations and take-home medication information, and by facilitating close communication among patients and other healthcare professionals. These efforts will help reduce the occurrence of ADRs and prevent ADR-related hospitalisations [17].5. References[1] Kommu S, Carter C, Whitfield P. Adverse Drug Reactions. [Updated 2024 Jan 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.[2] Wu TY, Jen MH, Bott le A, e t a l . Ten-year t rends in hospi tal admissions for adverse drug reactions in England 1999-2009. J R Soc Med. 2010;103(6):239-250. doi:10.1258/jrsm.2010.100113[3] Chan SL, Ang X, Sani LL, et al. Prevalence and characteristics of adverse drug reactions at admission to hospital: a prospective observational study. Br J Clin Pharmacol. 2 0 1 6 ; 8 2 ( 6 ) : 1 6 3 6 - 1 6 4 6 . d o i : 1 0 . 1111 /bcp.13081[4] Komagamine J . P reva lence o f u rgen t hospitalizations caused by adverse drug reactions: a cross-sectional study. Sci Rep 14, 6058 (2024). doi.org/10.1038/s41598-024-56855-z[5] H a k k a r a i n e n K M , H e d n a K , P e t z o l d M, Hägg S. Percentage of patients with p r e v e n t a b l e a d v e r s e d r u g r e a c t i o n s a n d p r e v e n t a b i l i t y o f a d v e r s e d r u g reactions--a meta-analysis . PLoS One. 2012;7(3):e33236. doi:10.1371/journal.pone.0033236[6] He Z, Cheong SH, Chan TF, Ieong SI, Chan KK. The incidence and characteris t ics of hospital izat ion due to adverse drug reactions: A single- centre retrospective analysis. Medical Journal of Kiang Wu. 2024, 24(2): 49-52. doi .org/10.12408/j.issn2223-4462.2024.02.013[7] S h e Q P, J u a n g X D , D i n g F, e t a l . Consequences, measurement, and evaluation of the costs associated with adverse drug reactions among hospitalized patients in China. BMC Health Serv Res. 2014;14:73. Published 2014 Feb 17. doi:10.1186/1472-6963-14-73 [8] Liao PJ, Mao CT, Chen TL, Deng ST, Hsu KH. Factors associated with adverse drug reaction occurrence and prognosis, and their economic impacts in older inpatients in Taiwan: a nested case-control study. BMJ Open. 2019;9(5):e026771. Published 2019 May 10. doi:10.1136/bmjopen-2018-026771[9] Gallagher RM, Kirkham JJ, Mason JR, et al. Development and inter-rater reliability of the Liverpool adverse drug reaction causa l i ty assessment tool . PLoS One. 2011;6(12):e28096. doi:10.1371/journal.pone.0028096[10] Bracken LE, Nunn AJ, Kirkham JJ, et al. Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool. PLoS One. 2017;12(1):e0169393.
The economic burden of adverse drug reactions-related hospitalisation: A single-centre retrospective analysis Volume 13 Número 1 Volume 13 Number 1 49Published 2017 Jan 3. doi:10.1371/journal.pone.0169393[11] . (2022). 2021( ). . [12] Patel TK, Patel PB, Bhalla HL, Dwivedi P, B a j p a i V, K i s h o r e S . I m p a c t o f s u s p e c t e d a d v e r s e d r u g r e a c t i o n s o n mortality and length of hospital stay in the hospitalised patients: a meta-analysis. Eur J Clin Pharmacol. 2023;79(1):99-116. doi:10.1007/s00228-022-03419-7[13] D o r m a n n H , M u t h - S e l b a c h U , K r e b s S, et al. Incidence and costs of adverse drug react ions dur ing hospi ta l i sa t ion: c o m p u t e r i s e d m o n i t o r i n g v e r s u s s t i m u l a t e d s p o n t a n e o u s r e p o r t i n g . D r u g S a f . 2 0 0 0 ; 2 2 ( 2 ) : 1 6 1 - 1 6 8 . doi:10.2165/00002018-200022020-00007[14] Sendekie AK, Kasahun AE, Limenh LW, Dagnaw AD, Belachew EA. Clinical and economic impact of adverse drug reactions in hospitalised patients: prospective matched nested case-control study in Ethiopia. BMJ Open. 2023;13(6):e073777. Published 2023 Jun 6. doi:10.1136/bmjopen-2023-073777[15] Chan SL, Ng HY, Sung C, et al. Economic burden of adverse drug reac t ions and potential for pharmacogenomic testing in Singaporean adults. Pharmacogenomics J. 2019;19(4):401-410. doi:10.1038/s41397-018-0053-1[16] R a m e s h M , P a n d i t J , P a r t h a s a r a t h i G. Adverse d rug reac t ions in a sou th Indian hospital--their severity and cost involved. Pharmacoepidemiol Drug Saf. 2003;12(8):687-692. doi:10.1002/pds.871[17] Janaje Munasinghe TM, Singer DR. Costs and prevention of adverse drug reactions. Eur J Intern Med. 2001;12(5):403-405. doi:10.1016/s0953-6205(01)00156-x
Chi Ian KUOK et al.Revista Médica de Macau Macao Medical Journal50Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literatureAbstractBackground: Intersphincteric resection (ISR) is the ultimate anus technique for the surgical treatment of very low rectal cancer [within 5cm from anal verge (AV) or within 2cm above the dentate line (DL)].Surgical treatment for low rectal cancer represents a challenge: to perform a radical resection and to preserve the sphincter's function.Methods and cases report: The aim of this review is to evaluate the outcomes of ISR. Reports published in the literature regarding surgical, oncological and functional outcomes were reviewed. We evaluated the outcomes after an intersphinceteric resection(ISR) for patients with low-lying rectal cancer. Reports published in the literature of the Pubmed online data-base and appropriate articles regarding surgical, oncological, and functional outcomes of an ISR were reviewed(1992-2024). In macau,between 2020/01 and 2024/08; our team did three selected cases of ISR (two cases of Type II tumor: -<2cm from Dental line and one case of Type III tumor: with internal anal sphincter invasion. Average age: 70 years old; the diagnostic was established by colonoscopy and malignancy confirmed by biopsy. Complete imaging was done using CT and MRI to establish the exact stage of the disease. One case of T2 low rectal cancer without CCRT Neo-adjuvant chemoRadiotherapy and directly process to surgery. Two cases of T3 above low rectal cancer received CCRT /Neo-adjuvant chemoRadiotherapy.The interdisciplinary individualized treatment began with neo-adjuvant CCRT(Total dose 50Gy /in 25 fractions IMRT was delivered to the rectal tumor, positive LN and lymphatic drainage region; concurrent chemotherapy using Xeloda 825mg/m2 was given during RT treatment) followed by surgery after eight weeks. Two cases of partial/subtotal ISRs and once case of total ISR were performed.Results: According to the reports; average local recurrence rates ranged from 4% to 13%, 5-year overall survival rate ranged from 62%-97%, and disease-free survival was 66%-87%, and functional outcomes: Stool frequency 24hours ranged from 2.2 to 14.5; Fecal urgency ranged from 4%-32%; Mean Wexner score ranged from 2.8 to 8.1; In macau; our team did three cases of ISR and average follow up time was36 months (20-56 months);there were no postoperative complications and the oncologic and functional results were good at 3 years follow-up. Local recurrence rates 0% (3 years); 3 year survival rates 100%; functional outcomes: stool frequency 24 hours ranged from 3-10, fecal urgency is 33%; mean wexner score range from 4-5/20 for General Surgery Department in Central Hospital, CHCSJ, Macau*Corresponding author: Chi Ian KUOK, E-mail: jimkuok@gmail.comDOI : 10.30224/MMJ.202601_13(1).0007Chi Ian KUOK*, Wai Lon NG
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literature Volume 13 Número 1 Volume 13 Number 1 51partial ISR (2 cases) and 8.5/20 for total ISR (one case)Conclusions: An ISR is a safe procedure for sphincter-saving rectal surgery in patient with very low rectal cancer; it does no compromise the oncological outcomes of the resection while the functional outcomes after ISR were found to be acceptable. In Macau, the result was comparable to datas reported in other area. The ISR technique is feasible/valid for selected patients with low rectal cancer and the results concerning about oncological and functional elements are compatible with the data published in the literature. Finally, patients must be selected very carefully for an ISR, the long-term functional outcome and quality of life still require further careful investigation.Keywords: Low Rectal Cancer; Intersphincteric Resection; Oncologic Outcome; Functional Outcome1. Introduction1.1 BackgroundThe low rectal cancer (LRC), is defined as tumors located within 5cm from anal verge (AV) or within 2cm above the dentate line (DL); Abdominoperineal resection(APR) with a permanent colostomy introduced by Sir Ernest Miles in 1908 for the treatment of low rectal cancers [below 5 cm from the anal verge(AV)], has long been the standard of care for rectal cancer in most surgical practices ever since. Anterior resection and its technical evolution, with the development of mechanical s taplers allowing a double stapling technique, was the first effective anus-preserving technique for rectal cancer.Tota l mesorec ta l exc is ion (TME) turned the tide for surgical treatment of rectal cancer. Heald et al. reported an oncological improvement between conventional surgery plus radiotherapy and TME alone with a reduction of the 5 years local recurrence (LR) rate (25 to 5%, respectively) and 5 years overall recurrence rate (62.7 to 22% respectively) for Dukes stage B2 and C. .The adopt ion of a mul t imodal t rea tment f o r r e c t a l c a n c e r w i t h t h e d e v e l o p m e n t o f neoadjuvantchemoradiotherapy (nCRT) protocols has furtherly improved the local recurrence rate allowing tumor down-stage with up to 20% of complete response.Intersphincteric resection (ISR) with hand-sewn coloanal anastomosis(CAA)introducedby Schiessel et al . , In1994, is the ultimate anus-preserving technique. [1]The surgical ISR technique has improved considerably in recent years with the dual objective of guaranteeing both the best oncological result and the best functional result without a permanent stoma.ISR is composed of two distinct phases (abdominal and perianal) consisting of TME and excision of the internal anal sphincter.1.2 Intershpincter ic resect ion: anatomical considerationsThe anorectal ring corresponds to the U-shaped sling ofstriated muscle from the puborectalis muscle that pullsanteriorly the rectum and delimits the beginning of thesurgical anal canal.The surgical anal canal extends from the anorectal ring to the anal verge and includes the external and internal sphincters.The anatomical anal canal is the distal part of the surgical anal canal and extends from the dental line to the anal verge.Rullier et al. Denost et al. and Bordeaux university Saint-Andre hospital have classified low rectal cancers into four categories to assist decision making between sphincter-saving surgery versus APR, and which type of sphincter-saving procedure to perform. It was originally classified into two types (subtotal and total ISR). 2 Studies conducted in Japan have further classified ISR into three types according to the extension of the resection:[2]; (Figure 1-3).
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literatureRevista Médica de Macau Macao Medical Journal52Type I low rectal cancers are supra-anal tumors, that is, lesions >1 cm from the anorectal ring/>2cm from Dental lineType II are juxta-anal tumors, that is, lesions <1 cm from the anorectal ring/<2cm from Dental line.Type III are intra-anal tumors, that is, lesions involved dental line/with internal anal sphincter invasion. Type IV aretransanal tumors , that is , lesions with external anal sphincter orlevatorani muscle invasion.In pract ice, ISR concerns type II and III lesions. Some authors have assessed for type IV tumors topropose ISR combined with partial resection of the externalsphincter.CAA (colon-anal anastomosis) – for type I low rectal cancer/>2cm from Dental line.Partial ISR: Incision at the level of the dentate line or just below, removing one-third or half of the internal sphincter.Subtotal ISR: Incision 1–2 cm below the dentate line, removing two third of the internal sphincter.resection line lays between the dentate line (DL) and the ISG and for Type II tumors, that is, lesions /<2cm from Dental line.Total ISR: Incision 2 cm below the dentate line, removing the entire internal sphincter. For Type III are intra-anal tumors, that is, lesions with internal anal sphincter invasion. Abdominoperineal resection of rectum (APR) for Type IV : Transanal tumors, that is, lesions with external anal sphincter or levatorani muscle invasion.Nowadays; ISR is only performed for Type II or type III; early low rectal cancer (T1/T2) only accept operation; but T3 tumor usually accept neo-adjuvant CCRT followed by operation 8 weeks later.Figure 1. Anatomy
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literature Volume 13 Número 1 Volume 13 Number 1 53Figure 3. Type of sphincter-saving surgeryFigure 2: Classified low rectal cancers and type of sphincter-saving surgery
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literatureRevista Médica de Macau Macao Medical Journal541.3 Indication of ISRIn 2012, Martin et al. identified the following indication.Criteria for ISR: rectal tumors with no evidence of extension into the External anal sphincter (EAS) and/or Levatorani Muscle (LAM); distal margin of at least 2 cm for T2/T3 tumors or 1 cm for T1 tumors; exclusion of poorly differentiated adenocarc inoma diagnosed by b iopsy and/or preoperative documented impaired fecal continence. These indication criteria were recently confirmed by a national based questionnaire evaluation conducted by the Japanese Society for Cancer of the Colon and Rectum(JSCCR).2. Methods and cases report:The aim of this review is to evaluate the outcomes of an ISR. Reports published in the l i terature regarding surgical , oncological and functional outcomes were reviewed. We evaluate the outcomes after an intersphinceteric resection(ISR) for patients with low-lying rectal cancer. Reports published in the literature of the Pubmed online data-base and appropr ia te ar t ic les regarding surgical, oncological, and functional outcomes of an ISR were reviewed(1992-2024).In Macau; Between 2020/01 and 2024/08; our team did three selected cases of ISR in 1) 2020/Jan; 2) 2021/Dec; 3) 2022/Dec (two cases of Type II tumor: -<2cm from Dental line and one case of Type III tumor: with internal anal sphincter invasion). Average age: 70 years old; the diagnostic was established by colonoscopy and malignancy confirmed by biopsy. Complete imaging was done using CT and MRI to establish the exact stage of the disease. One case of T2 low rectal cancer without CCRT Neo-adjuvant chemoRadiotherapy and directly process to surgery. Two cases of T3 above low rectal cancer received CCRT /Neo-adjuvant chemoRadiotherapy. The interdisciplinary individualized treatment began with neo-adjuvant CCRT(Total dose 50Gy /in 25 fractions IMRT was delivered to the rectal tumor, positive LN a n d l y m p h a t i c d r a i n a g e r e g i o n ; c o n c u r r e n t chemotherapy using Xeloda 825mg/m2 was given during RT treatment) followed by surgery after eight weeks. Two cases of partial/subtotal ISRs and once case of total ISR were performed.We performed intersphincteric rectal resection by a modified Schiessel technique.2.1 Morbidity and MortalityISR and colo-anal anastomosis associate with complications and mortality like any other colorectal operations. Reported Mortality and morbidity rates after an ISR range from 0% to 5% and from 7.7% to 32%, respectively, which are not significantly different from those reported after a low anterior resection (LAR) or APR. The common causes of death both surgery r e l a t e d f a c t o r ( e . g . a n a s t o m o t i c l e a k ) a n d consequence of comorbid medical condit ions (myocardial infarction, Pulmonary embolus) have been reported in the recently published meta-analysis.The most common and serious complication of ISR isanastomotic leakage which has been reported to affect 2.6%- 24% of patient undergoing colorectal surgery; and 0.9-13% of ISR surgery in the different s tudies . Anastomot ic leakage is managed by diverting ileostomy. Other complications includes anastomotic stricture, which may be the end result of anastomotic leakage or ischemia; fistula, pelvic sepsis, bleeding, bowel obstruction, and wound infections.In Macau: Our team did three cases of ISRFrom the data in our team (macau); post neo-ad juvan t re - s tag ing wi th MRI seemed : overestimated the Rectal T stage. e.g: 1) ycT2-3 N 0 M 0 ; v s y p T 0 N 0 M 0 ; 2 ) c T 2 N 0 M 0 ; v s pT1N0M0; 3) ycT3N0M0 vs ypT0N0M0; So; A precise per-operative staging should be the combination of rectal MRI, thoracic-abdomino-Pelvic computed tomography (CT) scan, and EUS, rigid proctoscopy and digital rectal examination (DRE) which are all crucial for a correct surgical indication.
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literature Volume 13 Número 1 Volume 13 Number 1 55In Average operation time: 4h30min The Postoperative evolutions ware favorable, without any complications, and the patients were d ischarged average (10+8+7 =8.3days) af ter surgery.there were no peri/postoperative death.3. Oncological OutcomesLocal control is one of the most important oncological objectives in surgery on patients with low-lying rectal cancer. Recurrence-free survival and overall survival after an ISR have also been steadily investigated to evaluate the oncologic safety of an ISR for patients with low rectal cancer.Local recurrence rates ranging from 4% to 13% have been reported following sphincter-saving resections for low rectal cancer. Several specialized studies have reported local recurrence rates that ranged from 0% to 12%.Survival: Recurrence-free survival and overall survival after an ISR have also been steadily investigated to evaluate the oncologic safety of an ISR for patients with low rectal cancer. Range of the 5-year overall survival rate of ISR was 62%-97%, and disease-free survival was 66%-87% in the different studies(table 2). Recently published study has reported that 5-year overall survival for patients after ISR was 80.2%, and disease-free survival was 69.1%.Involvement of the radial margin(Circumferential Margin- CRM)is the most important predictive factor for local recurrence after rectal cancer resection and is known to influence survival. Achieving negative radial margins for carcinomas that are located in the lower third of the rectum remains a challenge because at this level, the mesorectum is either thin or lacking. This is the main contraindication for a sphincter-saving resection in patients with T3 or above lower rectal tumors. The CRM to be obtained is similar to that of standard proctectomy(TME), i.e., CRM > 1mm in order to avoid the risk of local recurrence [3] and of distant metastases [4]mesorectum around the very low rectum. It is therefore important to be assured that the intersphincteric plane is not invaded by the tumor before proposing ISR withpreservation of the external sphincter.The DRM (Distal resection margins) has its own specificities for patients eligible for ISR. Because of the absence of mesorectum around the very low rectum, the risk of metastases in the mesorectum under the tumor is nil [5]. So, the expected benefit of a clear DRM is only for tumor resection and not for mesorectal excision.Recent studies have found that a DRM of 2 cm [6] and also 1 cm does not alter the oncological p r o g n o s i s w i t h [ 7 ] o r w i t h o u t p r e o p e r a t i v e radiotherapy [8]. To go even further, some studies question the value of a distal margin of 1 cm [9, 10].As an overview of the resection margins, a CRM > 1mm and a DRM 1 cm constitute the objectives. Since the resection cannot be laterally extended to the external sphincter (except in exceptional cases), invasion of the intersphincteric plane is a contraindication to ISR because CRM 1mm cannot be performed. At the opposite, DRM is rarely a contraindication to surgery since it is almost always possible to incise 1 cm below the lesion during ISR.PCRT (preoperative chemoradiotherapy/neo-adjuvant CCRT) decreases the tumor volume, induces downstaging, and faci l i tates surgical resec t ion . In addi t ion , PCRT t ransforms the tumor into an ulcerative scar, which may decrease intraoperative tumor seeding. The wide use of PCRT has facilitated the application of an ISR to patients with low rectal cancers. (Table 2)In Macau; our team did three cases of ISR and average follow up time is 36 months (20-56 months); 1)the first case did in 2020/01 : cT4N1M0; Post NA CCRT; ycT2-3N0M0; intra-operative anoscopy: Type II: tumor <2cm from dental line; post partial/subtotal ISR; post operative pathology: post CCRT change; no residual carcinoma seen. 1cm to distal margin; clear CRM margin ;ypT0N0M0. 2)The second case did in 2021/12; cT2N0M0; Intra-operative anoscopy: Type II tumor: 1cm from dental line. post partial/subtotal ISR; post operative pathology: 2.5cm to distal margin, clear CRM
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literatureRevista Médica de Macau Macao Medical Journal56Table 2. Oncological outcomes after an intersphincteric resection for patients with rectal cancer.Study Year Sample size (n) Distance to AV (cm) Follow-upduration(mo) PCRT (%) DRM(cm) 5-Year LRFS(%) 5-Year OS(%) 5-Year DFS(%) Braun 1992 63 - 80 - - 11 62 - Köhler 2000 31 1.3 82 0 1.6 9.7 79 - Rullier 2001 21 4.5 30 10 2.3 2 85 (3 yr) 85 (3 yr) Tiret 2003 26 4.25 39 38.5 1.6 3.4 96 - Saito 2004 35 0–2 23 57.1 1.3 1 - - Schiessel 2005 121 3 94 0 - 5.3 126.1 mo - Saito 2006 228 3.4 41 25 - 6.7 91.9 83.2 Chamlou 2007 90 3.5 56.2 41 1.2 6.6 82 75 Portier 2007 105 4.1 66.8 53.2 2.6 10.6 86.1 83.9 Akasu 2007 106 3 41 0 1.2 7.3 (3 yr) 95 (3 yr) - Weiser 2009 44 47 100 1.0 0 96 83 Park 2011 210 Lap (3.6), open (4.7) 34 Lap (7.7), open (1.3)Lap (1.5), open (1.4) Lap (2.6), open (7.7) - Lap (82.1), open (77) Laurent 2012 175 53 90.3 1.9 3.5 84 90 Baek 2013 84 Lap, (5.52); robotic,(4.39) 31.5 Lap(32,4); robotic,(42.6)Lap, (1.6); robotic(1.1)Lap,(5.4); robotic,(6.4)Lap,(90.7); robotic,(86.5) Lap,(81.2); robotic(80.6) Saito Kuo et al.Luca et alPark et alKim et alPiozzi et al2014 20142016201920202021199 3623147488123<53.8(1.5-5.0)3.2(2-5)2.8 1.03.3 1.73.1 0.878 2448728412024.6 78781005074- 2.2NRNR1.41.1 0.819.7 (7 yr)NRNRNRNR88.178.3 NRNRNR86.779.166.7 NRNR64.9(3yr)80.764.1DRM: Length of distal resection margin; OS: overall survival rate; DFS: disease-free survival rate; LRFS: local recurrence rate; Distance to AV: Tumor location from anal verge; margin; pT1N0M0. 3)the third case did in 2022/04; Type III tumor involved dental line :cT3-4N0M0; Post NA CCRT; ycT3N0M0. post Total ISR ; post operative pathology: post CCRT change; no residual carcinoma seen. 0.5cm to distal margin; Clear CRM margin . ypT0N0M0.All the oncologic results were good at 3 years follow up. Local recurrence rates 0% (3 years); 3 year survival rates 100%.
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literature Volume 13 Número 1 Volume 13 Number 1 574. Functional OutcomesThe aim of the ISR as an ultimate strategy of sphincteric conservation is to avoid permanent colostomy. Concerns exist about the long-term functional outcomes after an ISR, even though an ISR is technically feasible and oncologically safe. The high percentage of patients with anterior resection syndrome after stapled low colorectal or high coloanal anastomoses despite entire preservation of the anal sphincter, suggests that factors other than the anal sphincter are involved in incomplete fecal function after a rectal resection.Therefore the loss of the rectum and the internal anal sphincter expose the patient to both the consequences of conventional proctectomy as the low anterior resection syndrome or urogenital lesions and to specific continence dysfunction because of the internal sphincter resection. Anal dysfunction includes Urgency, Fecal incontinence (FI), Frequent bowel movements, stool fragmentation, soiling, sense of incomplete evacuation and is considered to be closed related to: Age, PCRT, location of anastomotic stoma, growth of anastomotic stoma, tumor stage, and resection of internal anal sphincter. The loss of rectal reservoir function seems to be a crucial factor that explains why the level of anastomosis has been reported to influence the quality of continence after a rectal resection. Based on experience with the ileal J-pouch, suggested suggestion was made that the functional results may improve after very low rectal resections because of an increased neorectal volume. Currently, the colonic pouch has short-term functional advantages tha t a re widely accepted , but few long term advantages. To obtain an overview of the anal function after an ISR, Martin et al. in their review of the literature found on average 2.7 bowel movements per 24h, 51.2% of patients had a perfect continence, 29.1% of patients reported fecal soiling, 23.8% an incontinence to flatus, 18.6% an urgentury, and 18.4% took antidiarrheal medications [11]. With a long-term follow-up, this functional results trend to improve over time [12].The impac t o f the ex ten t o f sph inc te r resection on the functional result is controversial in the literature. Ito et al. did not find any association between the extent of excision of the internal sphincter and an al terat ion of the funct ional function [13]. Even more surprisingly, Saito et al. did not observe an aggravation of the continence or of the quality of life between internal sphincter resection alone vs. internal sphincter resection with partial resection of external sphincter [14]. Kim et al (28-Robotic) evaluated anorectal function in patients aged <=75 years through fecal incontinence score(FIS) and manometry measured at baseline scores did not differ between partial and subtotal ISR but between total and partial/subtotal at 12 and 24 months. This difference shows that there is no difference in partial/subtotal IAS excision but there is a significant functional worsening after complete excision of the IAS (P<0.001-0.05). A multicentric Japanese study did report the same results as in this study analyzing 228 patients who underwent an ISR, patients with total intersphincteric resection displayed significantly worse continence than patients with partial or subtotal resection [15].P r e - o p e r a t i v e r a d i o c h e m o t h e r a p y represents an independent risk factor of continence dysfunction after ISR [16] and is associated with a lower colostomy-free survival [17]. It is supposed to be linked to pelvic ischemic changes and fibrosis; irradiation for mysenteric plexus lesion and restrain of impulse conduction. PCRT usually includes the anal sphincter in patients with low-lying rectal cancers the irradiation has a deleterious impact on anorectal function.Some authors have tried to explain the cause of fecal incontinence after an ISR by means of physiologic studies which have shown that removal of the internal anal sphincter is associated with a significant decrease in resting pressure. The
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literatureRevista Médica de Macau Macao Medical Journal58Maximum resting anal canal pressure is maintained by the internal anal sphincter.Anorectal manometry (ARM) is an objective e v a l u a t i o n a n d i s w i d e l y e m p l o y e d f o r t h e differential diagnosis of rest ing and pressure reduction in patients with FI. This exam helps to understand the mechanisms of the continence troubles affected by ISR. The Maximum Resting Pressure (MPR) measured by anorectal manometry is mainly assured at 55% by the internal sphincter anal , a l though the external sphincter and the hemorrhoidal plexus contribute, respectively, at 30 and 15% for the MPR. In a study assessing the performance of anorectal manometry before ISR in 68 patients, the elevated incidence of severe FI after ISR was independently related to a high MPR (>60 mmHg) before surgery and a high-pressure to subtotal/total ISR, patients after partial ISR had lower r isk of fecal incontinence and had significantly a higher MPR and a higher maximum squeeze pressure post-operatively. Funct ional resul ts a f ter ISR repor ted by several studies have been summarized in Table 3. In summary: functional outcomes: Stool frequency 24hours ranged from 2.2 to 14.5; Fecal urgency ranged from 4%-32%; Mean Wexner score ranged from 2.8 to 8.1;In Macau: We evaluated postoperative anal function by having patients fill out detailed questionnaires at 3, 6, 12, 24, 27, 36, 48 months after surgery. The questionnaires concerning anal function such as enhanced frequency of defecation urgent defecation, difficulty in defecation and FI. But these items has not been uniformed until now. The Jorge incontinence score, Kirwan grade, and Wexner score are frequently used assessments. We use the Wexner score system which also termed the Cleveland clinic Fecal incontinence severity scoring system (CCIS). It is a fecal incontinence score from 0-20; where 0 is perfect continence and 20 is complete incontinence. This score is based on questions related to incontinence of Gas, liquid and solid stool, as well as the need for lifestyle modifications/using antidiarrheal drugs and pad usage. Wenxer scores >=1 were considered to be symptomatic (1-4: mild incontinence, 5-8: moderate incontinence, 9-20: severe incontinence. The mean Wexnersocre at 12 months after stoma closure was 10.0. patients with frequent major soiling showed a wexner score of > or =16, and this score was used as a cutoff value of poor anal function.Our 3 cases of ISR: functional outcomes: stool frequency 24 hours ranged from 3-10, fecal urgency is 33%, mean wexner score range from 4-5 /20 for partial ISR (2 cases) and 8.5/20 for total ISR (one case); scores did not differ between partial and subtotal ISR but between total and partial/subtotal ISR. The patient with total ISR experienced worse anal dysfunct ion in 3 months (Wexner 11/20), but improved over time after symptomatic t reatment(ant i -diarrhea medicat ion) and anal exercise(Wexner 7/20 in 18 months).C l i n i c a l t e s t s s u c h a s a n a l m a n o m e t r y, defecography and electromyography can sometimes better delineate the mechanism for the FI, however, given the subjective nature of this symptom, these tests are not enough to accurately and consistently reflect the degree of incontinence experienced by the patient and its subjective impact of their QoL, nor can these tests determine the outcome of an intervention for FI. On the other hand; we don t have these exams in Macau and need to refer the case to other area if necessary. so far; the anal function of these cases are all acceptable. So we don t check any anal manometry till now. Functional results after ISR reported by several studies have been summarized in Table 3.
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literature Volume 13 Número 1 Volume 13 Number 1 595. ConclusionsAn ISR is a safe procedure for sphincter-saving rectal surgery in patient with very low rectal cancer; it does no compromise the oncological outcomes of the resection while the functional outcomes after ISR were found to be acceptable. In Macau; the cases for ISR is rare, but the result was comparable to data report in other area. The ISR technique is feasible/valid for selected patients with low rectal cancer and the results concerning about oncological and functional elements are compatible with the data published in the literature. Finally, patients must be selected very carefully for an ISR, the long-term functional outcome and quality of life still require further careful investigation.6. References[1] R u l l i e r E , D e n o s t Q , Ve n d r e l y V, R u l l i e r A , L a u r e n t C . L o w R e c t a l Cancer:Classification and Standardization of Surgery. Dis Colon Rectum. (2013)56:560–7. doi: 10.1097/DCR.0b013e31827c4a8c[2] Saito N, Moriya Y, Shirouzu K, Maeda K, Mochizuki H, Koda K,et al. Intersphincteric resection in patients with very low rectal cancer:a review of the Japanese experience. Dis Colon Rectum. (2006) 49:S13–22. doi: 10.1007/s10350-006-0598-y[3] Park JS, Huh JW, Park YA, Cho YB, Yun SH, Kim HC, et al. A circumferentialresection margin of 1mm is a negative prognostic factor in rectal cancerpatients with and without neoadjuvant chemoradiotherapy. Dis ColonRectum. (2014) 57:933–40. doi: 10.1097/DCR.0000000000000171[4] Tilly C, Lefèvre JH, Svrcek M, Shields C, Fléjou JF, Tiret E, et al. R1rectal resection: l o o k u p a n d d o n t l o o k d o w n . A n n Table 3. Functionaloutcomes after an intersphincteric resection for patients with rectal cancer.Study Feces-discriminationStool frequency/24hoursFecal urgency%Stool fragmentationNocturnal soiling%Pad wearingMean Wexner scoreAntidiarrhea medicationBraun [2] NR 2.2 22 NR NR 3 NR NRKöhler NR 3.3 NR NR NR 33.3 NR NRRullier NR 2.5 NR NR NR 9.5 NR NRBretagnol NR 2.8 NR NR NR 12 NR NRSaito NR 4 32 NR NR 0 NR NRSchiessel NR 14.5 NR NR NR NR NR NRYamada NR 5.0 NR NR NR NR 7.2 NRChamlou 21 2.3 16 40 24 38 NR NRDumont NR NR 7 NR NR NR 11 5Han2009 30 2.7 11 15 NR NR NR 14Kim 2016 NR 4.0 NR NR NR NR 6.7 NRKoyama2014 NR 3.7 NR NR NR NR 8.1 4Kuo2011Barisic2011Zhang2013.NRNR144.71.83.84NR128NR255NR94NR162.83.6NR6NRNR
Intersphincteric resection of rectum for low rectal cancer: Macau experience and a systematic review on the perioperative, oncological and functional outcomes of the literatureRevista Médica de Macau Macao Medical Journal60Surg. (2014) 260:794–800. doi: 10.1097/SLA.0000000000000988[5] Scott N, Jackson P, al-Jaberi T, Dixon MF, Quirke P, Finan PJ. Totalmesorectal excision and local ecurrence: a study of tumour spreadin the mesorectum distal to rectal cancer. Br J Surg. (1995) 82:1031–3. doi: 10.1002/bjs.1800820808[6] Pollett WG, Nicholls RJ. The relationship between the extent of distalclearance and survival and local recurrence rates after curative anteriorresection for carcinoma of the rectum. Ann Surg. (1983) 198:159–63. doi: 10.1097/00000658-198308000-00008[7] Ueno H ,Moch izuk i H , Hash iguch i Y, Ishikawa K, Fuj imoto H, Shinto E, e t al.Preoperative parameters expanding the indication of sphincter preservingsurgery in pa t i en t s w i th advanced low rec t a l cancer. Ann Surg. (2004) 239:34–42. doi: 10.1097/01.sla.0000103070.13030.eb[8] Bernstein TE, Endreseth BH, Romundstad P, Wibe A, Norwegian ColorectalCancer Registry. What is a safe distal resection margin in rectal cancerpatients treated b y l o w a n t e r i o r r e s e c t i o n w i t h o u t preoperative radiotherapy?Colorectal Dis. (2012) 14:e48–55. doi: 10.1111/j.1463-1318.2011.02759.x[9] M e z h i r J J , S h i a J , R i e d e l E , Te m p l e L K , N a s h G M , We i s e r M R , e t a l . W h o l e m o u n t p a t h o l o g i c a n a l y s i s o f r e c t a l c a n c e r f o l l o w i n g n e o a d j u v a n t therapy: impl ica t ions of margin s ta tus on long-term oncologic outcome. Ann Surg. (2012) 256:274–9. doi : 10.1097/SLA.0b013e31825c13d5[10] Rutkowski A, Nowacki MP, Chwalinski M, Oledzki J, Bednarczyk M,Liszka-Dalecki P, et al. Acceptance of a 5-mm distal bowel resectionmargin for rectal cancer: is i t safe? Colorectal Dis. (2012) 14:71–8. doi: 10.1111/j.1463-1318.2010.02542.x[11] Martin ST, Heneghan HM, Winter DC. Sys t ema t i c r ev i ew o f ou t comes a f t e r intersphincteric resection for low rectal cancer. Br J Surg. (2012) 99:603– 12. doi: 10.1002/bjs.8677[12] D e n o s t Q , L a u r e n t C , C a p d e p o n t M , Ze rb ib F, Ru l l i e r E . R i sk f ac to r s fo r fecal incontinence after intersphincteric resect ion for recta l cancer. Dis Colon Rectum. (2011) 54:963–8. doi: 10.1097/DCR.0b013e31821d3677[13] Ito M, Saito N, Sugito M, Kobayashi A, Nishizawa Y, Tsunoda Y. Analysis of clinical factors associated with anal function after intersphincteric resection for very low rectal cancer. Dis Colon Rectum. (2009) 52:64– 70. doi: 10.1007/DCR.0b013e31819739a0[14] Saito N, ItoM, Kobayashi A, Nishizawa Y, KojimaM, Nishizawa Y, et al. Longterm outcomes after intersphincteric resection for low-lying rectal cancer.AnnSurgOncol. (2014) 21:3608–15. doi: 10.1245/s10434-014-3762-y[15] Saito N, Moriya Y, Shirouzu K, Maeda K, Mochizuki H, KodaK,et al. Intersphincteric resection in patients with very low rectal cancer: a review of the Japanese experience. Dis Colon Rectum. (2006) 49:S13– 22. doi: 10.1007/s10350-006-0598-y[16] Ito M, Saito N, Sugito M, Kobayashi A, Nishizawa Y, Tsunoda Y. Analysis of clinical factors associated with anal function after intersphincteric resection for very low rectal cancer. Dis Colon Rectum. (2009) 52:64–70. doi: 10.1007/DCR.0b013e31819739a0[17] Hassan I, Larson DW, Wolff BG, Cima RR, Chua HK, Hahnloser D, et al.Impact of pelvic radiotherapy on morbidity and durability of sphincter preservation after coloanal anastomosis for rectal cancers. Dis Colon Rectum. (2008) 51:32–7. doi: 10.1007/s10350-007-9099-x
Cheng LEI et al. Volume 13 Número 1 Volume 13 Number 1 61Erythema multiforme caused by mycoplasma pneumoniae pneumonia in 2 childrenAbstractObjective: To summarize the clinical characteristics, diagnosis and treatment of erythema multiforme caused by Mycoplasma pneumoniae pneumonia.Methods: The data of clinical features, treatment of 2 children diagnosed with erythema multiforme caused by Mycoplasma pneumoniae infection and treated in Kiang Wu Hospital in 2024 were retrospectively analyzed, and related literature was reviewed.Results: The 2 patients suffered from fever, erythema multiforme and peunomia. Cutaneous lesions were manifested as diffuse erythematous rash. The symptoms in 2 cases were alleviated after the treatment with anti-Mycoplasma antimicrobials and symptomatic support. But one case was relieved with doxycycline whereas another case was alleviated with macrolides and steroid. None of them had sequelae during the follow-up.Conclusions: Mycoplasma pneumoniae can cause erythema multiforme in children. The mechanism is unclear yet. Early diagonsis , anti-Mycoplasma pneumoniae treatment and appropriate administration of glucocorticoid often lead to a good prognosis.Keywords: Mycoplasma pneumoniae; Erythema multiforme; Children*Corresponding author: Cheng LEI, E-mail: joycesumslei@gmail.comDOI : 10.30224/MMJ.202601_13(1).0008Cheng LEI*, Cho Ian WONG, Wan Teng CHOI2024 22 21 1
Erythema multiforme caused by mycoplasma pneumoniae pneumonia in 2 children Volume 13 Número 1 Volume 13 Number 1 632 23 1 4 2
2Revista Médica de Macau Macao Medical Journal642. Mycoplasma Pneumoniae, MP3~7[2] MP 3%~22.7%[3]77% 48%14% 12%9% MPMycoplasma Pneumoniae-induced Rash and Mucositis MIRMMIRMStevens-Johnson / (SJS/TEN) [4]21 2MP (EM) 10%/EMEM[5] EM MIRMStevens-Johnson Rowell [6]EMMPMP MP EMMP [5]MP EM9 (3 2 )[7] 1 2EMMP MMP EMEMMP-EM MP[8 9]MPMPEMEM EM9 2112 / /8MP3. [1] Waites KB, Xiao L, Liu Y, et al. Mycoplasma p n e u m o n i a e f r o m t h e R e s p i r a t o r y Tract and Beyond. Clin Microbiol Rev. 2017;30(3):747-809. doi:10.1128/CMR.
Erythema multiforme caused by mycoplasma pneumoniae pneumonia in 2 children Volume 13 Número 1 Volume 13 Number 1 6500114-16.[2] Narita M. Classification of Extrapulmonary M a n i f e s t a t i o n s D u e t o M y c o p l a s m a pneumoniae Infect ion on the Basis of Possible Pathogenesis. Front Microbiol. 2 0 1 6 ; 7 : 2 3 . P u b l i s h e d 2 0 1 6 J a n 2 8 . doi:10.3389/fmicb.2016.00023.[3] Meyer Sauteur PM, Theiler M, Buettcher M, et al. Frequency and Clinical Presentation of Mucocutaneous Disease Due to Mycoplasma pneumoniae Infection in Children With C o m m u n i t y - A c q u i r e d P n e u m o n i a . JAMA Dermatol. 2020;156(2):144-150. doi:10.1001/jamadermatol.2019.3602.[4] Canavan TN, Mathes EF, Frieden I, et al. Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. J Am Acad Dermatol. 2015;72(2):239-245. doi:10.1016/j.jaad.2014.06.026.[5] Zogha ib S , Kech ich i an E , Soua id K , et al. Triggers, clinical manifestations, and management of pediatric erythema multiforme: A systematic review. J Am Acad Dermatol. 2019;81(3):813-822. doi:10.1016/j.jaad.2019.02.057.[6] Soares A, Sokumbi O. Recent Updates in the Treatment of Erythema Multiforme. Medicina (Kaunas). 2021;57(9):921.[7] Prindaville B, Newell BD, Nopper AJ, et al . Mycoplasma pneumonia--associated m u c o c u t a n e o u s d i s e a s e i n c h i l d r e n : 2014;31(6):670-675. doi:10.1111/pde.12482.[8] Kechichian E, Dupin N, Wetter DA, et al. Erythema multiforme. EClinicalMedicine. 2024;77:102909.[9] Langley A, Anooshiravani N, Kwan S, Zeller J, Pope E. Erythema Multiforme in Children and Mycoplasma pneumoniae Aetiology. J Cutan Med Surg. 2016;20(5):453-457.
Ki LEUNG et al.Revista Médica de Macau Macao Medical Journal66Open peroral endoscopic myotomy: A case reportAbstractPeroral endoscopic myotomy (POEM) has become one of the standard treatments for esophageal achalasia. While POEM is associated with high success rates, there are instances where treatment failure may occur. The Open peroral endoscopic myotomy (O-POEM) technique retains the advantages of POEM but does not require the creation of a submucosal tunnel, allowing for selective myotomy. In this study, clinical success was achieved in a patient following O-POEM, as evidenced by a reduction in lower esophageal sphincter (LES) pressure, an improved Eckardt score, and favorable results from timed barium esophagram during follow-up. Importantly, there were no severe complications or recurrences observed throughout the nine-month follow-up period. Therefore, O-POEM appears to be a feasible, safe, and effective treatment option for achalasia after initial POEM failure. However, further follow-up is necessary to evaluate the long-term outcomes of O-POEM. Keywords: Achalasia; Open peroral endoscopic myotomy; Without endotracheal intubation 1Department of Gastroenterology, Conde de São Januário General Hospital, Macau2Department of Gastroenterology, Kiang Wu Hospital, Macau*Corresponding author: Teng CHEANG, E-mail: cheangteng@ssm.gov.mo DOI : 10.30224/MMJ.202601_13(1).0009Ki LEUNG*1, Teng CHEANG1*, Hoi Hung CHAN1, Ka Kei NG1, Kun Cheong CHOI1, Chin Wang CHIANG2, Hau Wai KWOK11. IntroductionAchalasia is a motility disorder characterized by the absence of peristalsis in the esophageal body and failure of relaxation of the lower esophageal sphincter (LES). Before the advent of peroral endoscopic myotomy (POEM)[1], Heller myotomy was the standard surgical treatment for achalasia. The world s first clinical case of POEM was success fu l ly per formed in 2008 [2]. Th is non-incisional, rapid, and minimally invasive endoscopic procedure has since become one of the most effect ive and potential ly permanent treatments for achalasia. The concept of POEM is similar to natural orifice transluminal endoscopic surgery (NOTES), utilizing a submucosal tunnel as the operative space. During the procedure, a longitudinal myotomy is performed on the circular muscles of the esophagus and stomach to reduce LES pressure. Patients who experience persistent or recurrent symptoms after initial POEM typically have an Eckardt symptom score of 4 or higher. Akintoye et al. reported that clinical success, defined as an Eckardt score of 3 or lower, was achieved in approximately 98% of patients after a mean follow-up of eight months post-POEM, indicating a failure rate of about 2%[3]. The primary causes of POEM failure include incomplete myotomy or muscle fibrosis. While re-POEM is considered a feasible and safe option for addressing failed POEM, the presence of fibrosis or scar formation can complicate the procedure. When performing
Open peroral endoscopic myotomy: A case report Volume 13 Número 1 Volume 13 Number 1 67re-POEM, it is essential to target unscarred areas of the esophagus, ensuring that previous operative sites are clearly identified[4]. In this article, we present two cases that illustrate how we managed patients who experienced failure after initial POEM or Heller myotomy. 1.1 Case 1 A 58-year-old woman with achalasia, diagnosed at 52, had a peroral endoscopic myotomy (POEM) three years ago. Initially, her post-operative Eckardt score was 0-1, but she later experienced worsening dysphagia, regurgitation, and heartburn, raising her score to 7. A repeat endoscopy showed a mildly dilated esophagus with a 2 cm white scar and an esophageal diverticulum. Manometry confirmed Type II achalasia. It was concluded that the initial POEM did not adequately address the posterior wall of the tightly constricted lower esophagus, leading to her ongoing symptoms.After discussing her condition, we proposed an Open peroral endoscopic myotomy (O-POEM) that avoids creating a submucosal tunnel. The procedure was performed without complications using a single-channel gastroscope (GIF-H290; Olympus Medical Systems Co, Tokyo, Japan), a hook knife (KD-620LR; Olympus), a CO2 insufflator (UCR; Olympus), and a high-frequency generator (VIO 300D; Erbe). The patient received intravenous general anesthesia without endotracheal intubation. We made a mucosal incision at the esophageal diverticulum site, injected normal saline, and carefully dissected the mucosa and muscle layers with the hook knife. Prophylact ic ant ibiot ics (Cefazolin 1 gram) were given intravenously 30 minutes before the procedure to prevent infection. The O-POEM procedure lasted 23 minutes, involving a 7 cm myotomy extending at least 3 cm into the cardia. After ensuring hemostasis, we closed the mucosal incision. The patient began a liquid diet on day three and was discharged on day seven. By the fourteenth day, she returned to a regular diet. Over nine months, her symptoms comple te ly reso lved . Fo l low-up eva lua t ions at one, three, and six months included barium esophagram, endoscopy, and manometry, showing the disappearance of the bird s beak sign, mucosal healing, and a lower esophageal sphincter (LES) p res su re o f 13 mmHg. She r ema ined symptom-free, with an Eckardt score of 0, after six years. 1.2 Case 2 A 27-year-old man with a history of achalasia underwent Heller myotomy at age 5 and several endoscopic balloon dilatations. Diagnosed with Down syndrome at birth and achalasia at five, he reported intermittent vomiting and dysphagia during a pediatric follow-up. By age 31, his Eckardt score rose to 5. A barium swallow study showed persistent achalasia with mild stenosis in the distal esophagus, and manometry confirmed Type I achalasia. After discussing treatment options with his parents, the decision was made to proceed with peroral endoscopic myotomy (POEM) to help relieve his ongoing symptoms. During the pre-POEM endoscopy assessment, the esophageal lumen appeared dilated, with a relatively narrow opening at the esophagogastric junction. However, the endoscope passed through without any resistance. A diverticulum was noted on the posterior wall of the lower esophagus. Following further discussions with his family, an Open peroral endoscopic myotomy (O-POEM) procedure under conscious sedation was proposed. During the O-POEM procedure, an incision was made in the esophageal mucosa, extending from 37 cm to 43 cm from the incisors, following a submucosal injection of a mixture of normal saline and sodium hyaluronate solution at the posterior wa l l o f the lower esophagus . Myotomy was performed from 38 cm to 43 cm from the incisors using a hook knife. The O-POEM procedure was completed without complications. Since then, he has been regularly followed up in the gastroenterology outpatient department for the past five years, reporting significant improvement in his symptoms, with an Eckardt score of 1.
Open peroral endoscopic myotomy: A case reportRevista Médica de Macau Macao Medical Journal682. DiscussionThe Open pe ro ra l endoscop ic myo tomy (O-POEM) technique offers the advantages of t radi t ional POEM without the need to create a submucosal tunnel , making i t a promis ing treatment option for patients with achalasia who have experienced failure after initial POEM[5]. In our cases, a distal esophageal diverticulum was identified, suggesting that the previous myotomy was insufficient. We located the mucosal incision si te direct ly at the divert iculum, a detai l not previously reported in the literature (search terms: peroral endoscopic myotomy and repeat on PubMed). During the procedures, we carefully dissected the mucosa, submucosal fibers, and circular muscle layer to enhance the prior myotomy site. The route taken during the ini t ia l POEM procedure may result in fibrosis, which complicates subsequent procedures performed at the same si te . This f ibrosis increases the diff icul ty of creating the submucosal tunnel. Consequently, the majority of re-POEM procedures typically select an alternative route; for instance, if the initial approach was anterior, the subsequent approach may be posterior or lateral. In our cases, post-POEM diverticula are predominantly associated with inadequate myotomy. The o-POEM approach is favored due to its directness and efficiency in addressing complications resulting from post-POEM procedures. D u r i n g e n d o s c o p y, t h e m a n a g e m e n t o f ventilation and airway safety varies significantly between genera l anes thes ia (GA) and awake sedation. In GA, the patient is fully unconscious, requiring advanced airway management techniques, such as endotracheal in tubat ion . Vent i la t ion is closely monitored, and the anesthesia team must be ready to address compl ica t ions l ike airway obstruction or respiratory depression. In contrast, awake sedation allows patients to remain conscious and responsive, facil i tat ing spontaneous breathing and airway protection. The risk of airway obstruction is reduced, as patients can react to stimuli and maintain their airway reflexes. Furthermore, awake sedation allows for quicker preparation and shorter recovery times post-endoscopy. Given the expedited nature of the o-POEM procedure compared to traditional POEM, awake sedation is more effective and carries fewer anesthetic risks for patients. According to the l i terature, the expected procedure time for O-POEM is approximately 20 minutes; in our cases, one patient was under general anesthesia without endotracheal intubation and another one was under conscious sedation, which has not been widely documented in previous reports (search terms: peroral endoscopic myotomy and anesthesia on PubMed). Overall, O-POEM has emerged as a viable option for treating achalasia following initial POEM failure. However, more O-POEM cases are needed to assess the long-term outcomes of this technique.
Open peroral endoscopic myotomy: A case report Volume 13 Número 1 Volume 13 Number 1 69Figure 1. a) An esophageal diverticulum was found at posterior wall of tightly lower esophagus. b) Mucosotomy performed after submucosal saline injection. c) Cutting off the submucosal fibers and circular layer of the esophagus. d) Without endotracheal intubation during performed procedure. e) Gastroscopic view of postoperative cardia shows healing mucosa in the area of O-POEM during follow up. f) The barium esophagram was observed during follow-up one month later, revealed disappearance of bird beak sign.
Open peroral endoscopic myotomy: A case reportRevista Médica de Macau Macao Medical Journal70g) Scar of previous Heller myotomy h) barium esophagram showed bird beak sign during follow-up. i) Endoscopy showed dilatation of esophageal lumen and a diverticulum at posterior wall of lower esophagus and gastric cardia stenosis. j and k) The length of myotomy was 7cm and at least 3 cm distal to the G-E junction. l)Procedure performed without endotracheal intubation.
Open peroral endoscopic myotomy: A case report Volume 13 Número 1 Volume 13 Number 1 713. References[1] Zaninotto G, Costantini M, Portale G et al. Etiology, diagnosis, and treatment of failures after laparoscopic Heller myotomy for achalasia. Ann Surg. 2002;235(2):186-92. doi: 10.1097/00000658-200202000-0 0 0 0 5 . P M I D : 1 1 8 0 7 3 5 7 ; P M C I D : PMC1422413.[2] Inoue H, Minami H, Kobayashi Y et al. Perora l endoscopic myotomy (POEM) for esophagea l acha las ia . Endoscopy. 2010;42(4):265-71. doi: 10.1055/s-0029-1244080 . Epub 2010 Mar 30 . PMID: 20354937.[3] Inoue H, Shiwaku H, Iwakir i K e t a l . Clinical practice guidelines for peroral e n d o s c o p i c m y o t o m y. D i g E n d o s c . 2 0 1 8 ; 3 0 ( 5 ) : 5 6 3 - 5 7 9 . d o i : 1 0 . 1111 /den.13239. PMID: 30022514.[4] Zaninotto G, Bennett C, Boeckxstaens G et al, Low DE. The 2018 ISDE achalasia guidelines. Dis Esophagus. 2018;31(9). doi: 10.1093/dote/doy071. PMID: 30169645.[5] Liu W, Zeng HZ, Chen HL et al . Open peroral endoscopic myotomy (O-POEM) for the treatment of achalasia. Dis Esophagus. 2017;30(10):1-2. doi: 10.1093/dote/dox070. PMID: 28859393.
Hou Man LO et al.Revista Médica de Macau Macao Medical Journal72A case of dupilumab as a steroid-sparing agent in a patient with vesicular bullous pemphigoid and new-onset diabetes mellitus AbstractBullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder predominantly affecting the elderly, manifests classically with pruritic urticarial plaques and tense bullae on trunk/extremity flexures. Recognized clinical variants include vesicular, nodular, and dyshidrosiform subtypes. We describe a 56-year-old male exhibiting pruritic vesiculopapular eruptions (<1cm) across face, neck, trunk, and extremities. Diagnostic confirmation revealed elevated anti-BP180 antibodies, peripheral eosinophilia, subepidermal blistering on histopathology, and linear IgG/C3 deposition at the basement membrane zone (BMZ) via direct immunofluorescence (DIF). Combination therapy with methylprednisolone and Dupilumab achieved complete symptomatic resolution within 12 weeks, sustained through 12-month follow-up, and allowed for rapid corticosteroid tapering. The combination of interleukin (IL)-4/13 inhibition with systemic corticosteroids demonstrates significant steroid-sparing efficacy in this case of vesicular BP with comorbid new-onset diabetes, effectively reducing the risks associated with prolonged steroid use.Keywords: Vesicular pemphigoid; Bullous pemphigoid; Dupilumab; IL-4/IL-13 inhibitor; Treatment1Department of Dermatology, Peking University Third Hospital, Beijing, China2Chao’s Medical Centre, Macao 3Kiang Wu Nursing College of Macau*Corresponding author: Hou Man LO, E-mail: lohoumandoctor@163.comDOI : 10.30224/MMJ.202601_13(1).0010Hou Man LO1*, Ian CHAO2, I CHAO3, Wo On CHAO21. IntroductionBullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder, primarily affecting elderlies. The classic manifestations features pruritic urticarial plaques progressing to tense serous bullae on truncal and flexural surfaces, typically negative for Nikolsky sign. About 80% of cases show IgG autoantibodies targeting BP180/BP230 antigens at the basement membrane, but diagnostic complexity arises in variants like vesicular (VBP), nodular, and dyshidrosiform subtypes. VBP presents diagnostic challenges due to its polymorphic vesiculopapular eruptions, mimicking dermatitis herpetiformis and linear IgA bullous dermatoses. Management is complicated by comorbidities and corticosteroid-related complications. Recent advances in BP pathogenesis have led to novel therapies, including the combination of Dupilumab with systemic cort icosteroids, which enhances eff icacy and reduces steroid-related adverse effects in patients with comorbidities that contraindicate long-term steroid use.Herein, we present a case of vesicular bullous pemphigoid in a patient with new-onset type 2 diabetes mellitus in which the patient showed a rapid response and remission of pruritus following
A case of dupilumab as a steroid-sparing agent in a patient with vesicular bullous pemphigoid and new-onset diabetes mellitus Volume 13 Número 1 Volume 13 Number 1 73treatment with combined systemic corticosteroids and Dupilumab, which facilitated rapid steroid tapering.2. Case ReportA 56-year-old Chinese male presented in May 2024 with pruritic erythematous macular eruptions initially confined to the abdomen. Delayed medical consultation precipitated rapid centrifugal spread to face, neck, and extremities within 7 days. Lesions progressed to multiple serous-filled vesicles (< 1 cm) on urticarial plaques with Nikolsky's negativity, evolving into erosion and crusts formation (Fig 1 A-C). Prior misdiagnosis as tinea corporis with terbinafine and topical steroids for two weeks yielded no improvement. Medical history revealed hyperlipidemia treated with atorvastatin 20 mg daily for five years and developed type 2 diabetes mellitus six months before BP onset, currently managed with metformin 1000 mg daily. Persistent lesions progression prompted referral to our center for hospitalization in June 2024.A skin biopsy was performed on a vesicle of his right forearm, hematoxylin-eosin staining revealed intraepidermal spongiosis, vacuolar degeneration of basal keratinocytes, and subepidermal blister formation, superficial dermis demonstrated diffuse infiltrates composed of lymphocytes, histiocytes, a c c o m p a n i e d b y a b u n d a n t e o s i n o p h i l s a n d neutrophils (Fig 2 A-B). Direct immunofluorescence displayed linear IgG and C3 deposition at the BMZ (Fig 2 C-D). An elevated serum anti-BP180 level of 224.653 units/mL (normal range: <20 units/mL) and peripheral eosinophils of 1.17*109/L (normal range: 0-0.8*109/L) was noted. According to the above findings, a diagnosis of vesicular BP was made, with a score of 45 in Bullous Pemphigoid Disease Area Index (Moderate).Accord ing to the 2022 Guide l ines for the management of bul lous pemphigoid by the European Academy of Dermato logy and Venereology [1], the patient was deemed refractory to topical cor t icos teroid therapy. The ac tual usage exceeded the safety limit (>40 g/day), and new lesions persisted after two weeks. Given the ineffectiveness of topical steroids and the progression of skin lesions despite escalating to intravenous methylprednisolone at 40 mg daily for one week, a s t ronger t reatment approach was warranted. Considering the patient's new-onset diabetes and the imperative to minimize systemic corticosteroid exposure, in line with the Diagnosis and treatment of bullous pemphigoid: an expert consensus statement (2025 edition) [2], we initiated Dupilumab treatment, starting with a subcutaneous loading dose of 600 mg, followed by 300 mg injections every two weeks until one year, alongside topical halometasone and fusidic acid creams. Two weeks after the first Dupilumab injection, the patient showed marked improvement in both the blisters and pruritus. After the sixth dose, the lesions completely resolved, with no recurrence during the one-year follow-up (Fig 1 D-I). Systemic corticosteroids were gradually tapered from 40 mg/day to 32 mg/day by week 4, then to 24 mg/day by week 6, with a stepwise reduction of 4 mg/day every three weeks thereafter. Throughout this process, there were no recurrences or worsening of the condition, with a total duration of systemic corticosteroid therapy of 23 weeks.
A case of dupilumab as a steroid-sparing agent in a patient with vesicular bullous pemphigoid and new-onset diabetes mellitusRevista Médica de Macau Macao Medical Journal74Figure 1. Clinical Presentation Comparison: Pre-Treatment vs. Post-Treatment Status.(A, B, C) Diffuse distribution of multiple small, tense serous vesicles (<1 cm) overlying urticarial plaques with erythematous bases, some of the vesicles ruptured and leaving erosion and crusting. (D, E, F) After combination therapy of corticosteroids and subcutaneous Dupilumab for 12 weeks, the initial lesions were completely resolved and remaining hyperpigmented patches.3. DiscussionBP was f i r s t de l inea ted in the 1950s to d i f f e r e n t i a t e s u b e p i d e r m a l b l i s t e r i n g f r o m pemphigus' intraepidermal acantholysis, classically presents with Nikolsky's sign-negative tense bullae on erythematous/urticarial plaques. While typically diagnosable, emerging clinical variants (e.g. , vesicular, dyshidrosiform subtypes) now contribute to rising misdiagnosis rates, mimicking other autoimmune blistering disorders and necessitating r igorous h i s topa tho log ica l conf i rmat ion fo r definitive diagnosis.Vesicular bullous pemphigoid, a rare variant of BP, was first described by Bean et al . [3] in 1976, where seven patients initially misdiagnosed with atypical DH were correctly diagnosed through skin biopsy and immunofluorescence. This underscores the importance of considering BP, DH, and LABD in the differential diagnosis of vesiculobullous diseases. Additionally, pemphigus, particularly the pemphigus herpetiformis variant characterized by grouped vesicles, should be considered. However, pemphigus is distinguished by intraepidermal acantholysis on histology, intercellular IgG and/or C3 deposition on DIF, and circulating anti-desmoglein antibodies, all of which were absent in our case. In the present case, skin biopsy revealed subepidermal separation with mixed inflammatory infiltrates dominated by eosinophils, along with linear IgG and C3 deposition at the BMZ and elevated serum anti-BP180 antibodies, confirming BP. DH is distinguished by granular IgA deposition and anti-transglutaminase 3 IgA antibodies, while
A case of dupilumab as a steroid-sparing agent in a patient with vesicular bullous pemphigoid and new-onset diabetes mellitus Volume 13 Número 1 Volume 13 Number 1 75Figure 2. Histopathological features and immunofluorescence result of the skin biopsy.(A, B) Skin biopsy result showing intraepidermal spongiosis, vacuolar degeneration of basal keratinocytes, and subepidermal blister formation (Red stars), superficial dermis demonstrated diffuse infiltrates composed of lymphocytes, histiocytes, accompanied by abundant eosinophils (Yellow arrows) and neutrophils. (Hematoxylin-eosin stain; original magnification: 40) DIF test showed a linear IgG (C) and C3 (D) deposition at the BMZ.LABD features linear IgA deposition and anti-XVII collagen IgA antibodies.Systemic and topical corticosteroids remain first-line treatments for BP, often yielding positive results . However, long-term or high-dose use poses significant risks, particularly for elderly patients with comorbidities such as neurological disorders, malignancy, and metabolic syndrome.[4] Prolonged corticosteroid therapy may worsen hyperg lycemia , d i abe tes , hyper t ens ion , and stroke r isk, underscoring the urgent need for safer alternatives. In this case, the patient's recent diagnosis of type 2 diabetes mellitus presented a s ign i f i can t con t ra ind ica t ion to long- te rm, high-dose systemic cort icosteroids. Although alternative therapies including methotrexate and mycophenolate mofetil are strongly recommended by guidelines, their potential for hepatotoxicity, bone marrow suppression, and increased infection risk were concerning in the context of managing a new metabolic disorder. After a thorough discussion of the risks and benefits, the patient declined these conventional immunosuppressants. We therefore opted for dupilumab, a targeted biologic with a more favorable safety profile, to act as a steroid-sparing agent and facilitate rapid corticosteroid tapering. R e c e n t r e s e a r c h h a s h i g h l i g h t e d t h a t a p redominan t type-2 in f lammatory response , driven by Th2 cells, plays a central role in BP pathogenesis. [5] Th2-related cytokines such as IL-4 and IL-13 are overexpressed in lesional skin,
A case of dupilumab as a steroid-sparing agent in a patient with vesicular bullous pemphigoid and new-onset diabetes mellitusRevista Médica de Macau Macao Medical Journal76promoting autoantibody production, eosinophil recruitment, and inflammation. Dupilumab, a recombinant humanized IgG4 monoclonal antibody targeting the IL-4/IL-13 receptor, is widely used for atopic dermatitis and has demonstrated a strong safety profi le, with only mild adverse events including self-limited conjunctivitis, injection site reactions, and headache. In this patient, the introduction of Dupilumab as combination therapy allowed for a rapid and significant reduction in both the duration and total cumulative dose of corticosteroids, thereby mitigating the risk of worsening his metabolic syndrome. This outcome supports the use of Dupilumab as an effective and safe steroid-sparing strategy for BP patients with comorbidities that preclude the use of conventional immunosuppressants or long-term steroids.Regarding prognostic indicators, the level of anti-BP180 and eosinophil has been associated with the severity of BP. In this case, after achieving complete resolution, the patient s serum anti-BP180 antibody and peripheral eosinophil levels decreased to 15.268 units/mL and 0.34 109/L, respectively, further supporting their value as reliable markers of prognosis.4. ConclusionI n c o n c l u s i o n , t h i s c a s e d e m o n s t r a t e s Dupilumab's efficacy as a steroid-sparing agent in a patient with vesicular BP and comorbid diabetes, achieving complete lesion resolution without recurrence over 12 months of fo l low-up. By significantly reducing the adverse effects associated with systemic corticosteroids through dual IL-4/IL-13 blockade, Dupilumab highlights Th2-targeted therapy as a safe and precise strategy for BP patients requiring rapid steroid minimization due to comorbidities. However, as a single case report with combination therapy, these results cannot establish the generalizability or independent efficacy and safety of Dupilumab. Further investigations are needed. 5. References[1] Borradori L, Van Beek N, Feliciani C, et al . Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol . 2022;36(10):1689-1704. DOI:10.1111/jdv.18220.[2] China Dermatologist Association, Chinese Society of Dermatology, et al. Diagnosis and treatment of bullous pemphigoid: an expert consensus statement (2025 edition). Chin. J. Dermatol, 2025, 58(5): 405-415. DOI: 10.35541/cjd.20240622.[3] B e a n S F, M i c h e l B , F u r e y N , e t a l . Vesicular pemphigoid. Arch Dermatol . 1976;112(10):1402-1404. DOI: 10.1001/archderm.1976.01630340020005.[4] Zhang B, Chen X, Liu Y, et al. Relationship between bullous pemphigoid and metabolic syndrome: a 12-year case-control study conducted in China. Ther Adv Chronic D i s . 2 0 2 2 ; 1 3 : 2 0 4 0 6 2 2 3 2 2 11 3 0 7 0 7 . DOI:10.1177/20406223221130707.[5] Z h a n g L , C h e n Z , Wa n g L , e t a l . Bul lous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy. Front Immunol. 2023; 14:1115083. DOI:10.3389/fimmu.2023.1115083
