Search

BackgroundRecently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy.MethodsWe conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity.ResultsA total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression.ConclusionPD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

Since the emergence of the virulent coronavirus in 2019, efforts to tackle the coronavirus-disease-2019 (COVID-19) pandemic have been made globally. The development of the coronavirus disease (COVID) vaccine was a significant breakthrough in ways to tackle the virus. Various research studies have been conducted to identify how the virus works and ways to manage COVID, including the efficacy of the vaccines. However, there is limited data on how these measures work for the immunocompromised, despite the grave impact of these virulent strains in this population. Specifically, this review aims to focus on kidney transplant recipients (KTRs). Studies have suggested that there is significantly lower vaccine response in some immunocompromised groups despite additional booster doses, and hence warrants an augmented or alternative protection against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for these patients. This suggests a need for alternative or more tailored approach in providing adequate protection against the COVID-19 in these cohorts. Some suggested ways include withholding immunosuppressants before and/or after vaccination, increasing the vaccine doses or reducing intervals and providing a mixture of monoclonal antibody (mAb) or antiviral therapy. However, the appropriate degree of alteration and augmentation, as well as its safety and effectiveness remains to be determined. Furthermore, continuous emergence of more virulent strains, such as the Omicron and its sub-lineages or the Deltacron, emphasises the need for ongoing research to assess the effectiveness of the current treatment against these new variants. Overall, active interest and appropriate updates to COVID-19 guidelines is necessary.

Background/Aims: As risk of colorectal neoplasm is varied even in persons with “average-risk,” risk evaluation and tailored screening are needed. This study aimed to evaluate the risk factors of high-risk adenoma (HRA) in healthy individuals and determine the characteristics of advanced neoplasia (AN) among individual polyps.Methods: Asymptomatic adults who underwent the first lifetime screening colonoscopy at the Seoul National University Hospital Healthcare System Gangnam Center (SNUH GC) were recruited from 2004 to 2007 as SNUH GC Cohort and were followed for 10 years. Demographic and clinical characteristics were compared between the subjects with and without AN (≥10 mm in size, villous component, and/or high-grade dysplasia and/or cancer) or HRA (AN and/or 3 or more adenomas). For individual polyps, correlations between clinical or endoscopic features and histologic grades were evaluated using a decision tree method.Results: A total of 6,047 subjects were included and 5,621 polyps were found in 2,604 (43%) subjects. Advanced age, male sex, and current smoking status were statistically significant with regards to AN and HRA. A lower incidence of AN was observed in subjects taking aspirin. In the decision tree model, the location, shape, and size of the polyp, and sex of the subject were key predictors of the pathologic type. A weak but significant association was observed between the prediction of the final tree and the histological grouping (Kendall's tau-c = 0.142, p < 0001).Conclusions: Advanced neoplasia and HRA can be predicted using several individual characteristics and decision tree models.

Background:Clonorchis sinensis (CS) infection is considered a group 1 carcinogen of cholangiocarcinoma (CCA). There were very few studies regarding clinical characteristics of CS-associated CCA (CACC). This study aimed to investigate clinical characteristics of patients with CCA with or without CS infection.Methods: A total of 367 patients diagnosed with CCA who underwent diagnostic tests for CS infection were enrolled. CS infection was defined as follows: at least one positive serum ELISA test, skin test, stool microscopy, or bile microscopy.Results: There were 95 (26%) patients with CS infections. The median follow-up duration was 14.9 months (range, 6.07–36.17). The following significant differences were noted among patients with CACC compared to non-CACC; diagnosis at younger age (median 62 years vs. 65 years, p = 0.018), higher male to female ratio (83.2 vs. 61.8%, p < 0.001), and residence in CS-endemic area (46.3 vs. 25.4%, p = 0.014). Univariate analysis of prognostic factors indicated that tumor location, curative resection, tumor stage, and laboratory tests including CA 19-9, CEA, and bilirubin were significantly associated with overall survival, but CS infection was not. In multivariate analysis, tumor location, CEA, curative resection and tumor stage were identified as independent prognostic factors. Among patients under age 64, CACC group had lower survival rate than non-CACC group (p = 0.022).Conclusions: CACC had the following significant characteristics compared to non-CACC; diagnosis at younger age, higher male to female ratio, higher prevalence in CS endemic areas and poorer overall survival in patients under age 64.

Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.