The risk of free flap revision and subsequent medical costs in patients with hypopharyngeal cancer.

BACKGROUND: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. METHODS: A 20-year retrospective case-control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. RESULTS: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12-5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. CONCLUSIONS: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population.

The Effect and Mechanism of Astragalus Polysaccharides on T Cells and Macrophages in Inhibiting Prostate Cancer.

BACKGROUND: The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated. METHODS: This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS's effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays. RESULTS: It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8+ T cells. At a concentration of 5 mg/mL, APS activated both CD4+ and CD8+ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4+ and PD-1+ CD8+ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4+ T cells, and CD8+ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8+ T cells, RAW 264.7 cells, or THP-1 cells. CONCLUSION: The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

Microbial Analysis in Chronic Rhinosinusitis Patients with Chronic Kidney Disease and End-Stage Renal Disease.

INTRODUCTION: This study aimed to elucidate the bacterial profile of chronic rhinosinusitis (CRS) in patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) compared with nonrenal patients, guiding antibiotic selection for clinicians. METHODS: We retrospectively analyzed 13,906 inpatients from the Chang Gung Research Database who underwent sinus surgery (2004-2018). Patients were categorized into ESRD-CRS, CKD-CRS, and non-CKD-CRS based on the estimated glomerular filtration rate. Bacterial cultures from surgical samples were classified as facultative anaerobes or aerobes (e.g., Klebsiella pneumoniae [KP], Pseudomonas aeruginosa [Ps.a]), anaerobes, and fungi and ranked by prevalence. RESULTS: Data from 47 ESRD-CRS, 230 CKD-CRS, and 13,123 non-CKD-CRS patients were analyzed. In ESRD-CRS, the predominant species were KP (31.6%), Ps.a (21.1%), and Coagulase-negative Staphylococcus (CoNS, 15.8%). CKD-CRS showed Staphylococcus epidermidis (27.7%), CoNS (20.5%), and Ps.a (20.5%). Non-CKD-CRS had Staphylococcus epidermidis (29.8%), CoNS (25.0%), and Staphylococcus aureus (15.5%). For anaerobes, ESRD-CRS was dominated by Fusobacterium nucleatum (10.5%) and Peptostreptococcus micros (10.5%), whereas CKD-CRS and non-CKD-CRS showed Propionibacterium acnes as a primary strain (14.5% and 28.7%, respectively). CONCLUSION: For CRS in ESRD, antibiotics targeting KP and Fusobacterium nucleatum are recommended. In CKD-CRS, a focus on Staphylococcus epidermidis and Propionibacterium acnes is suggested. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

The Value of the Nutritional Indicators in Predicting Free Flap Failure From a Multicentre Database.

OBJECTIVE: Nutritional and inflammatory statuses have been associated with complications in microvascular-free flaps during head and neck surgeries. This study aimed to evaluate the potential of nutritional indicators in predicting postoperative free flap complications. STUDY DESIGN: We conducted a 20-year retrospective, case-control study within a defined cohort. SETTING: The study involved head and neck cancer patients from the Chang Gung Research Database who underwent simultaneous tumor ablation and free flap wound reconstruction between January 1, 2001, and December 31, 2019. METHODS: We employed logistic regression and stratified analysis to assess the risk of free flap complications and the subsequent need for flap revision or redo in relation to nutritional indicators and other clinical variables. RESULTS: Of the 8066 patients analyzed, 687 (8.5%) experienced free flap complications. Among these, 197 (2.4%) had free flap failures necessitating a redo of either a free flap or a pedicled flap. Beyond comorbidities such as chronic obstructive pulmonary disease, end-stage renal disease, and a history of prior radiotherapy, every 10-unit decrease in the preoperative prognostic nutritional index (PNI) was consistently associated with an increased risk of both free flap complications and failure. The covariate-adjusted odds ratios were 1.90 (95% confidence interval [CI]: 1.42-2.54) and 1.89 (95% CI: 1.13-3.17), respectively. CONCLUSION: A lower preoperative PNI suggests a higher likelihood of microvascular free flap complications in head and neck surgeries. Further randomized controlled trial designs are required to establish causality.

A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Clinical Value of Endoscopic Esophageal Screening in Head and Neck Squamous Cell Carcinoma Patients.

OBJECTIVE: To investigate the clinical benefit of routine esophageal screening in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. METHODS: This retrospective study selected newly diagnosed HNSCC patients from the Chang Gung Research Database between January 2007 and December 2019. Patients who underwent endoscopic esophageal examinations within 2 months of the initial diagnosis of HNSCC were included in the screening group. The clinical outcomes of the screening and nonscreening groups were analyzed. RESULTS: In total, 13,627 HNSCC patients were included, comprising 1032 females and 12,640 males (mean age 55.0 years), and the esophageal screening group included 7033 (51.4%) patients. The prevalence rate of esophageal tumors was 4.5%. Hypopharyngeal cancer patients were the most likely to have (13.4%) second primary esophageal tumors. The American Joint Committee on Cancer stage of the esophageal tumor was lower in the esophageal screening group than in the nonesophageal screening group. The oral, oropharyngeal, and hypopharyngeal cancer patients in the esophageal screening group had better survival outcomes than their counterparts in the nonesophageal screening group. CONCLUSION: Endoscopic esophageal screening of newly diagnosed HNSCC patients can detect esophageal tumors at an early stage and improve overall survival. Esophageal screening could be a routine survey in HNSCC patients, particularly those with lifestyle risk factors and in countries with a high prevalence of esophageal cancer.

Does repetitive dilatation and curettage or hysteroscopic biopsy in patients treated with progestins for endometrial hyperplasia or carcinoma affect subsequent fetomaternal outcomes? A population-based study using the National Health Insurance Research Database of Taiwan.

OBJECTIVE: To investigate the impact of repeated dilatation and curettage or hysteroscopic biopsy on fetomaternal outcomes in patients receiving progestin treatment for endometrial hyperplasia or early-stage carcinoma. METHOD: This was a population-based study using the Taiwan National Health Insurance Research Database between 2009 and 2017 of women who gave birth and had a history of endometrial hyperplasia and early-stage carcinoma treated with progestins. Logistic regression analysis was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) reflecting the association between repeated procedures and fetomaternal outcomes. RESULTS: A total of 6956 women with 8690 deliveries were identified. Compared with those who had two or fewer procedures, women who received more than two procedures had a significantly higher risk for cervical insufficiency (aOR, 5.09 [95 CI, 2.31-11.24]). Furthermore, women who had more than two procedures were prone to have adverse neonatal outcomes, including Apgar score < 7 at 1 min (aOR, 1.97 [95% CI, 1.13-3.43]) and 5 min (aOR, 3.11 [95% CI, 1.33-7.23]) and preterm delivery <32 weeks (aOR, 2.86 [95% CI, 1.50-5.45]). CONCLUSION: Undergoing more than two procedures was associated with subsequent maternal cervical insufficiency, preterm delivery <32 weeks, and low neonatal Apgar score. Health care providers should be aware of the potential risks and balance the benefits and harms of repeated procedures.

Induction of ferroptosis and apoptosis in endometrial cancer cells by dihydroisotanshinone I.

Danshen, also known as Salvia miltiorrhiza, is a medicinal herb used in traditional Chinese medicine. Its potential impact on endometrial cancer has not been thoroughly investigated. This study aimed to examine the effect of dihydroisotanshinone I (DT), a compound found in Danshen, on the viability of ARK1 and ARK2 endometrial cancer cells and its mechanisms. The results showed that 10 µM DT inhibited cell viability of ARK1 and ARK2 cells by inducing apoptosis and ferroptosis, which was achieved by blocking the expression of GPX4. In vivo experiments using a xenograft nude mouse model indicated that DT treatment significantly reduced tumor volume without causing any adverse effects. These findings suggest that DT may be a potential therapeutic agent for inhibiting endometrial cancer cell viability, but further research is needed to confirm these results.

The Impact of Clinical Prognosis of Viral Hepatitis in Head and Neck Cancer Patients Receiving Concurrent Chemoradiotherapy.

This study evaluated the clinical characteristics of head and neck cancer (HNC) patients with hepatitis B (HBV) or hepatitis C (HCV) who underwent concurrent chemoradiotherapy (CCRT) and examined the prognostic impact of antiviral therapies. In a 19-year retrospective analysis of 8224 HNC patients treated with CCRT, 29.8% (2452) were diagnosed with HBV or HCV, of whom 714 received antiviral therapy. For non-metastatic HNC patients on CCRT, factors such as gender, Charlson Comorbidity Index (CCI), liver cirrhosis markers (Fibrosis-4, APRI), and initial tumor stage were significant determinants of their overall survival. However, the presence of HBV or HCV and the administration of antiviral treatments did not yield distinct survival outcomes. In summary, antiviral therapy for HBV or HCV did not affect the 5-year survival rates of non-metastatic HNC patients undergoing CCRT, while gender, tumor stage, CCI, and liver cirrhosis were notable prognostic indicators.

Survival Evidence of Local Control for Colorectal Cancer Liver Metastases by Hepatectomy and/or Radiofrequency Ablation.

Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.

Comparison of Fungal and Non-Fungal Rhinosinusitis by Culture-Based Analysis.

BACKGROUND: Incidence of fungal rhinosinusitis has increased in recent few years. We investigated the differences in microbiological findings between patients with fungal and non-fungal rhinosinusitis by growing microbiological cultures from samples obtained from sinus surgery. METHODS: Using the Chang Gung Research Database, we enrolled all chronic rhinosinusitis (CRS) patients who had ever undergone sinus surgery from 2001 to 2019 and had microbiological culture during sinus surgery. Enrolled patients were divided into fungal and non-fungal groups, based on fungal culture and surgical pathology. RESULTS: A total of 898 patients were diagnosed with fungal rhinosinusitis and 2884 with non-fungal rhinosinusitis. The fungal group had a higher age distribution (56.9 ± 13.1 vs. 47.0 ± 14.9), a larger proportion of females (62.4% vs. 37.0%), more unilateral lesions (80.4% vs. 41.6%), a lower incidence of the need for revision surgery (3.6% vs. 6.0%, p = 0.004), and a higher proportion of Pseudomonas aeruginosa in the culture (14.3% vs. 4.6%, p < 0.001). CONCLUSIONS: This large-scale study showed that Pseudomonas aeruginosa are more commonly found in patients with fungal rhinosinusitis and in patients who needed revision surgery, suggesting that efforts aimed at eliminating Pseudomonas are needed in order to improve the disease outcomes of patients with fungal rhinosinusitis.

Recurrence of pediatric intussusception: A nationwide population-based descriptive study in Taiwan.

Intussusception is frequently observed pediatric emergency that is often followed by recurrent intussusception after initial treatment. This study investigated the risk factors associated with recurrent intussusception in children aged ≤ 3 years. Between January 2007 and December 2015, a cohort study was conducted by linking the Taiwan Maternal and Child Health Database to the Birth Certificate Application database and the National Health Insurance Research Database in Taiwan. Patients aged ≤ 3 years with intussusception diagnosis and related treatment were included in our study. Multivariable logistic regression was used to analyze the risk factors associated with recurrent intussusception. In total, 5341 children with intussusception aged ≤ 3 years were enrolled in our cohort. The adjusted odds ratio (aOR) for recurrent intussusception in children aged 2 to 3 years was 0.62 (95% confidence interval [CI]: 0.47-0.82) compared with children aged < 1 year, and surgery decreased the risk of recurrent intussusception (aOR = 0.64, 95% CI: 0.46-0.88). Male patients had higher risk of recurrent intussusception than female patients had (aOR = 1.41, 95% CI: 1.13-1.75). Higher birth weight may increase the risk of recurrent intussusception, but this association was not statistically significant. Furthermore, gestational age did not seem to affect the risk of recurrent intussusception. Surgical treatment and delayed onset of intussusception are associated with a reduced risk of recurrent intussusception; males are associated with increased risk of recurrent intussusception. In addition, we suggest that in early infancy, patients who received non-surgical treatment as the initial treatment for intussusception should be closely followed up for potential recurrence of intussusception.

Prevalence, Characteristics, and Treatment of Hemorrhoids During Pregnancy: A Nationwide Population-Based Cohort Study in Taiwan.

Background: Hemorrhoids, a gastrointestinal tract disorder, are common during pregnancy. However, large-scale epidemiological studies on hemorrhoids during pregnancy are limited. Therefore, this study used analyzed data from a nationwide population-based database to investigate the prevalence, characteristics, and treatment of hemorrhoids in Taiwan. Materials and Methods: This retrospective population-based study used data from the National Health Insurance Research Database and Taiwan Birth Certificate Application to collect the medical records of women who were pregnant at any time during 2009-2018. Hemorrhoids was defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) (455. X) and International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) (K64.X, O22.4X) with related treatment. Results: We enrolled 1,608,804 deliveries in 1,070,708 women. The proportion of hemorrhoids increased with age in both primipara and multipara women. Of the pregnant women, 31% received oral medication, and 93.2% used the topical ointment to treat their hemorrhoids. Few patients (1.8%) required procedure or surgery during pregnancy, and 41.4% of those patients underwent procedure or surgery in their first trimester. The cumulative incidence of hemorrhoids during pregnancy was significantly higher in women with a history of hemorrhoids and those with multifetal pregnancies. No significant difference in the incidence of hemorrhoids was observed between multiparous and primiparous women. Conclusion: Women with a history of hemorrhoids or those carrying multiple fetuses had an increased risk of hemorrhoids during pregnancy. The most commonly used treatment for hemorrhoids during pregnancy was topical ointments, with only a small proportion (1.8%) of patients requiring procedure or surgery.

Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea.

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes-best-corrected visual acuity (BCVA) and central macular thickness (CMT)-were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.

Evaluation of Infective Endocarditis in Children: A 19-Year Retrospective Study in Taiwan.

BACKGROUND: Infective endocarditis (IE) is an important cause of morbidity and mortality in pediatric patients with heart disease. Little literature has explored differences in the presentation of endocarditis in children with and without heart disease. This study aimed to compare the clinical outcomes and determine the risk of in-hospital death in the study population. METHODS: Data were retrospectively collected from 2001 to 2019 from the Chang Gung Research Database (CGRD), which is the largest collection of multi-institutional electronic medical records in Taiwan. Children aged 0-20 years with IE were enrolled. We extracted and analyzed the demographic and clinical features, complications, microbiological information, and outcomes of each patient. RESULTS: Of the 208 patients with IE, 114 had heart disease and 94 did not. Compared to those without heart disease, more streptococcal infections (19.3% vs. 2.1%, p < 0.001) and cardiac complications (29.8% vs. 6.4%, p < 0.001) were observed in patients with heart disease. Although patients with heart disease underwent valve surgery more frequently (43.9% vs. 8.5%, p < 0.001) and had longer hospital stays (28.5 vs. 12.5, p = 0.021), their mortality was lower than that of those without heart disease (3.5% vs. 10.6%, p = 0.041). Thrombocytopenia was independent risk factor for in-hospital mortality in pediatric patients with IE (OR = 6.56, 95% CI: 1.43-40.37). CONCLUSION: Among pediatric patients diagnosed with IE, microbiological and clinical features differed between those with and without heart disease. Platelet counts can be used as a risk factor for in-hospital mortality in pediatric patients with IE.

Appraisal of lung cancer survival in patients with end-stage renal disease.

Introduction: The survival outcome of lung cancer patients with end-stage renal disease has been poorly studied in the literature. In this study, we evaluated the effect of end-stage renal disease on lung cancer survival. Material and methods: A retrospective, multicenter, matched-cohort study of lung cancer patients with end-stage renal disease under renal replacement therapy (WITH-ESRD) and without end-stage renal disease (WITHOUT-ESRD) was performed. One WITH-ESRD patient was matched to four WITHOUT-ESRD patients. Results: Baseline clinical characteristics did not differ statistically significantly after matching between the WITH-ESRD and WITHOUT-ESRD groups. WITH-ESRD included 133 patients and WITHOUT-ESRD included 532 patients. Kaplan-Meier survival analysis demonstrated no significant difference in median overall survival between WITH-ESRD patients and WITHOUT-ESRD patients (7.36 months versus 12.25 months, respectively, p = 0.133). Lung cancer WITH-ESRD patients receiving medical treatment had a median overall survival of 5.98 months (95% CI: 4.34-11.76) compared to 14.13 months (95% CI: 11.30-16.43) for WITHOUT-ESRD patients, p = 0.019. Although patients receiving surgical treatment compared to those receiving medical treatment had an improvement of survival by 46% (HR = 0.54, 95% CI: 0.19-1.53, p = 0.243), the difference did not reach statistical significance. Cox regression analysis revealed that male gender and stage IIIA-IV were independent factors associated with poor outcome for WITH-ESRD patients. Conclusions: In our limited experience, the survival for lung cancer with ESRD is not inferior to lung cancer patients without ESRD. The reasons for poor survival for the WITH-ESRD medical treatment group and late diagnosis despite frequent medical visits merit further investigation.

6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma.

Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.

Direct-Acting Antivirals Reduce the De Novo Development of Esophageal Varices in Patients with Hepatitis C Virus Related Liver Cirrhosis.

The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 (61.4%) patients achieved DAA induced-SVR and 83 (38.6%) did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1−30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030) and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression was strongly correlated with the presence of baseline EV (p < 0.001). To the best of our knowledge, this is the first study to demonstrate that DAA-induced SVR is associated with decreased risk of de novo EV occurrence and progression in the real world.

Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis.

BACKGROUND & AIMS: The comparative risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) receiving tenofovir disoproxil fumarate (TDF) vs. entecavir (ETV) remains controversial. In this individual patient data (IPD) meta-analysis, we aimed to compare HCC risk between the two drugs and identify subgroups who may benefit more from one treatment than the other. METHODS: Published meta-analyses, electronic databases and congress proceedings were searched to identify eligible studies through January 2021. We compared HCC risk between the two drugs using a multivariable Cox proportional hazards model with anonymised IPD from treatment-naïve patients with CHB receiving TDF or ETV for ≥1 year. Treatment effect consistency was explored in propensity score matching (PSM), weighting (PSW) and subgroup analyses for age, sex, hepatitis B e-antigen (HBeAg) positivity, cirrhosis and diabetes status. RESULTS: We included 11 studies from Korea, Taiwan and Hong Kong involving 42,939 patients receiving TDF (n = 6,979) or ETV (n = 35,960) monotherapy. Patients receiving TDF had significantly lower HCC risk (adjusted hazard ratio [HR] 0.77; 95% CI 0.61-0.98; p = 0.03). Lower HCC risk with TDF was consistently observed in PSM (HR 0.73; 95% CI 0.59-0.88; p <0.01) and PSW (HR 0.83; 95% CI 0.67-1.03; p = 0.10) analyses and in all subgroups, with statistical significance in the ≥50 years of age (HR 0.76; 95% CI 0.58-1.00; p <0.05), male (HR 0.74; 95% CI 0.58-0.96; p = 0.02), HBeAg-positive (HR 0.69; 95% CI 0.49-0.97; p = 0.03) and non-diabetic (HR 0.79; 95% CI 0.63-1.00; p <0.05) subgroups. CONCLUSION: TDF was associated with significantly lower HCC risk than ETV in patients with CHB, particularly those with HBeAg positivity. Longer follow-up may be needed to better define incidence differences between the treatments in various subgroups. IMPACT AND IMPLICATIONS: Previous aggregate data meta-analyses have reported inconsistent conclusions on the relative effectiveness of tenofovir disoproxil fumarate and entecavir in reducing hepatocellular carcinoma risk in patients with chronic hepatitis B (CHB). This individual patient data meta-analysis on 11 studies involving 42,939 patients from Korea, Taiwan and Hong Kong suggested that tenofovir disoproxil fumarate-treated patients have a significantly lower hepatocellular carcinoma risk than entecavir-treated patients, which was observed in all subgroups of clinical interest and by different analytical methodologies. These findings should be taken into account by healthcare providers when determining the optimal course of treatment for patients with CHB and may be considered in ensuring that treatment guidelines for CHB remain pertinent.