OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p < 0.001), recurrent urinary tract infections (p = 0.013), and leg lymphedema (p = 0.038). Age over 50-year (HR = 9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR = 7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR = 5.13; 95% CI, 1.38–19.1) and DSS (HR = 5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p = 0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.
Cohort Studies* ; Endometrial Neoplasms* ; European Union ; Female ; Gynecology ; Humans ; Hysterectomy ; Leg ; Lymphedema ; Neoplasm Grading ; Obstetrics ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies* ; Urinary Tract Infections ; Uterine Neoplasms

BACKGROUNDThe public vaccination program of hepatitis B virus (HBV) was launched during 1984 in Taiwan, China. However, the long-lasting protective efficacy of HBV vaccination among adolescents older than 15 years of age was seldom recorded.

METHODSA seroepidemiological survey was conducted among 4575 first-year university students in Taiwan, China during 2000 to 2003, including the serological data of HBV by testing HBV surface antigen (HBsAg), surface antibody (anti-HBs), HBV core antibody (anti-HBc) and demographic information.

RESULTSHBsAg carrier rate among male university students born before the initiation of the HBV vaccination program decreased from 12.8% to 4.8% among those born after the vaccination program (P < 0.001, chi(2) test for linear trend). Similarly, HBsAg carrier rate among female university students born before the initiation of the HBV vaccination program decreased from 8.1% to 2.7% among those born after the vaccination program (P < 0.001, chi(2) test for linear trend). Both male and female students in eastern Taiwan had the highest HBsAg carrier rate compared with the other places. Using multiple logistic regression analysis, compared with students born after July 1984, the adjusted OR of HBsAg carrier rate decreased from 3.10 for students born before June 1981 to 1.56 for students born from July 1983 to June 1984 (95% CI 1.96 - 4.91, P < 0.001; 95% CI 1.06 - 2.28, P = 0.024; respectively).

CONCLUSIONSPublic vaccination provides long-lasting protection again HBV infection among the university students in Taiwan, China older than 18 years of age. There is a geographic variation of HBV infection among young adults in Taiwan, China.

Adolescent ; Adult ; Carrier State ; epidemiology ; Female ; Hepatitis B ; epidemiology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Male ; Mass Vaccination ; Taiwan ; epidemiology ; Time Factors

OBJECTIVE: To investigate the changes of incidence and prognosis of epithelial ovarian cancer in thirty years in Taiwan. METHODS: The databases of women with epithelial ovarian cancer during the period from 1979 to 2008 were retrieved from the National Cancer Registration System of Taiwan. The incidence and prognosis of these patients were analyzed. RESULTS: Totally 9,491 patients were included in the study. The age-adjusted incidences of epithelial ovarian cancer were 1.01, 1.37, 2.37, 3.24, 4.18, and 6.33 per 100,000 person-years, respectively, in every 5-year period from 1979 to 2008. The age-specific incidence rates increased especially in serous, endometrioid and clear cell carcinoma, and the age of diagnosis decreased from sixty to fifty years old in the three decades. Patients with mucinous, endometrioid, or clear cell carcinoma had better long-term survival than patients with serous carcinoma (log rank test, p<0.001). Patients with undifferentiated carcinoma or carcinosarcoma had poorer survival than those with serous carcinoma (log rank test, p<0.001). The mortality risk of age at diagnosis of 30-39 was significantly higher than that of age of 70 years or more (test for trend, p<0.001). The mortality risk decreased from the period of 1996-1999 (hazard ratio [HR], 0.90; p=0.054) to the period after 2000 (HR, 0.74; p<0.001) as compared with that from the period of 1991-1995. CONCLUSION: An increasing incidence and decreasing age of diagnosis in epithelial ovarian cancer patients were noted. Histological type, age of diagnosis, and treatment period were important prognostic factors for epithelial ovarian carcinoma.
Carcinoma ; Carcinosarcoma ; Female ; Humans ; Incidence ; Mucins ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Prognosis ; Taiwan

INTRODUCTIONDecreased insulin action (insulin resistance) is crucial in the pathogenesis of type 2 diabetes. Decreased insulin action can even be found in normoglycaemic patients, and they still bear increased risks for cardiovascular disease. In this study, we built models using data from metabolic syndrome (Mets) components and the oral glucose tolerance test (OGTT) to detect insulin resistance in subjects with normal glucose tolerance (NGT).

MATERIALS AND METHODSIn total, 292 participants with NGT were enrolled. Both an insulin suppression test (IST) and a 75-g OGTT were administered. The steady-state plasma glucose (SSPG) level derived from the IST was the measurement of insulin action. Participants in the highest tertile were defined as insulin-resistant. Five models were built: (i) Model 0: body mass index (BMI); (ii) Model 1: BMI, systolic and diastolic blood pressure, triglyceride; (iii) Model 2: Model 1 + fasting plasma insulin (FPI); (iv) Model 3: Model 2 + plasma glucose level at 120 minutes of the OGTT; and (v) Model 4: Model 3 + plasma insulin level at 120 min of the OGTT.

RESULTSThe area under the receiver operating characteristic curve (aROC curve) was observed to determine the predictive power of these models. BMI demonstrated the greatest aROC curve (71.6%) of Mets components. The aROC curves of Models 2, 3, and 4 were all substantially greater than that of BMI (77.1%, 80.1%, and 85.1%, respectively).

CONCLUSIONA prediction equation using Mets components and FPI can be used to predict insulin resistance in a Chinese population with NGT. Further research is required to test the utility of the equation in other populations and its prediction of cardiovascular disease or diabetes mellitus.

Adult ; Blood Glucose ; Cross-Sectional Studies ; Female ; Glucose ; metabolism ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; Male ; Metabolic Syndrome ; metabolism ; Middle Aged ; Models, Statistical

Objective: This study aimed to evaluate the clinical outcomes and cost-effectiveness of dual-energy X-ray absorptiometry (DXA) for osteoporosis screening. Materials and Methods: Eligible patients who had and had not undergone DXA screening were identified from among those aged 50 years or older at Kaohsiung Veterans General Hospital, Taiwan. Age, sex, screening year (index year), and Charlson comorbidity index of the DXA and non-DXA groups were matched using inverse probability of treatment weighting (IPTW) for propensity score analysis. For cost-effectiveness analysis, a societal perspective, 1-year cycle length, 20-year time horizon, and discount rate of 2% per year for both effectiveness and costs were adopted in the incremental cost-effectiveness (ICER) model. Results: The outcome analysis included 10337 patients (female:male, 63.8%:36.2%) who were screened for osteoporosis in southern Taiwan between January 1, 2012, and December 31, 2021. The DXA group had significantly better outcomes than the non-DXA group in terms of fragility fractures (7.6% vs. 12.5%, P < 0.001) and mortality (0.6% vs. 4.3%, P < 0.001). The DXA screening strategy gained an ICER of US$ -2794 per quality-adjusted life year (QALY) relative to the non-DXA at the willingness-to-pay threshold of US$ 33004 (Taiwan’s per capita gross domestic product). The ICER after stratifying by ages of 50–59, 60–69, 70–79, and ≥ 80 years were US$ -17815, US$ -26862, US$ -28981, and US$ -34816 per QALY, respectively. Conclusion Using DXA to screen adults aged 50 years or older for osteoporosis resulted in a reduced incidence of fragility fractures, lower mortality rate, and reduced total costs. Screening for osteoporosis is a cost-saving strategy and its effectiveness increases with age. However, caution is needed when generalizing these cost-effectiveness results to all older populations because the study population consisted mainly of women.

Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

Purpose: The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods: From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results: A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

Background/Aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). Conclusions Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Conclusions Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.