Clinical studies support the efficacy of programmed cell death 1 (PD-1) targeted therapy in a subset of patients with metastatic gastric cancer (mGC). With the goal of identifying determinants of response, we performed molecular characterization of tissues and circulating tumor DNA (ctDNA) from 61 patients with mGC who were treated with pembrolizumab as salvage treatment in a prospective phase 2 clinical trial. In patients with microsatellite instability-high and Epstein-Barr virus-positive tumors, which are mutually exclusive, dramatic responses to pembrolizumab were observed (overall response rate (ORR) 85.7% in microsatellite instability-high mGC and ORR 100% in Epstein-Barr virus-positive mGC). For the 55 patients for whom programmed death-ligand 1 (PD-L1) combined positive score positivity was available (combined positive score cut-off value ≥1%), ORR was significantly higher in PD-L1(+) gastric cancer when compared to PD-L1(-) tumors (50.0% versus 0.0%, P value <0.001). Changes in ctDNA levels at six weeks post-treatment predicted response and progression-free survival, and decreased ctDNA was associated with improved outcomes. Our findings provide insight into the molecular features associated with response to pembrolizumab in patients with mGC and provide biomarkers potentially relevant for the selection of patients who may derive greater benefit from PD-1 inhibition.

INTRODUCTION Colorectal surgery has been associated with a complication rate of 15-20% and mean postoperative inpatient stays of 6-11 days. The principles of enhanced recovery after surgery (ERAS) are well established and have been developed to optimise perioperative care and facilitate discharge. The purpose of this systematic review is to present an updated review of perioperative care in colorectal surgery from the available evidence and ERAS group recommendations. METHODS Systematic searches of the PubMed and Embase ™ databases and the Cochrane library were conducted. A hand search of bibliographies of identified studies was conducted to identify any additional articles missed by the initial search strategy. RESULTS A total of 59 relevant studies were identified. These included six randomised controlled trials and seven clinical controlled trials that fulfilled the inclusion criteria. These studies showed reductions in duration of inpatient stays in the ERAS groups compared with more traditional care as well as reductions in morbidity and mortality rates. CONCLUSIONS Reviewing the data reveals that ERAS protocols have a role in reducing postoperative morbidity and result in an accelerated recovery following colorectal surgery. Similarly, both primary and overall hospital stays are reduced significantly. However, the available evidence suggests that ERAS protocols do not reduce hospital readmissions or mortality. These findings help to confirm that ERAS protocols should now be implemented as the standard approach for perioperative care in colorectal surgery.

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Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.Graphical Abstract

Background Misdiagnosis of the severity of acute appendicitis may lead to perforation and can consequently result in increased morbidity and mortality. In this study, the role of hyperbilirubinemia as a predictor of perforation is assessed by performing a meta-analysis of diagnostic accuracy. Methods A systematic search of the literature published over the past 20 years was performed using the EMBASE, PubMed, Cochrane library, and Google Scholar databases. Results Low values of sensitivity, specificity, and diagnostic odds ratio (DOR) were detected: 0.21 (95% confidence interval (CI): 0.13 - 0.30, standard error (SE) = 0.43), 0.27 (95% CI: 0.15 - 0.43, SE = 0.73), and 0.10 (95% CI: 0.3 - 0.28, SE = 0.05), respectively. The positive likelihood ratio (PLR) was low (0.29 (95% CI: 0.27 - 0.91, SE = 0.76)), whereas the negative likelihood ratio (NLR) was high (2.88 (95% CI: 1.66 - 5.14, SE = 0.10)). The hierarchical summary receiver operating characteristic curve was positioned towards the lower right corner, and the area under the curve was 0.19, both indicating a low level of overall accuracy and discrimination. Compared with the PLR, the negative inverse likelihood ratio (1/LR - ) indicated that a positive result has a greater impact on the odds of disease than does a negative result. Conclusions Hyperbilirubinemia alone is not a reliable tool to predict perforation. Future studies should investigate whether the combined predictive values of bilirubin, C-reactive protein (CRP), and white blood cells are a more effective diagnostic tool.