Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

Gallstones are a common public health problem, especially in developed countries. There are an increasing number of patients who are diagnosed with gallstones due to increasing awareness and liberal use of imaging, with 22.6%-80% of gallstone patients being asymptomatic at the time of diagnosis. Despite being asymptomatic, this group of patients are still at life-long risk of developing symptoms and complications such as acute cholangitis and acute biliary pancreatitis. Hence, while early prophylactic cholecystectomy may have some benefits in selected groups of patients, the current standard practice is to recommend cholecystectomy only after symptoms or complications occur. After reviewing the current evidence about the natural course of asymptomatic gallstones, complications of cholecystectomy, quality of life outcomes, and economic outcomes, we recommend that the option of cholecystectomy should be discussed with all asymptomatic gallstone patients. Disclosure of material information is essential for patients to make an informed choice for prophylactic cholecystectomy. It is for the patient to decide on watchful waiting or prophylactic cholecystectomy, and not for the medical community to make a blanket policy of watchful waiting for asymptomatic gallstone patients. For patients with high-risk profiles, it is clinically justifiable to advocate cholecystectomy to minimize the likelihood of morbidity due to complications.

Background: Acute cholangitis (AC) is a common emergency with a significant mortality risk. The Tokyo Guidelines (TG) provide recommendations for diagnosis, severity stratification, and management of AC. However, validation of the TG remains poor. This study aims to validate TG07, TG13, and TG18 criteria and identify predictors of in-hospital mortality in patients with AC. Methods: This is a retrospective audit of patients with a discharge diagnosis of AC in the year 2016. Demographic, clinical, investigation, management and mortality data were documented. We performed a multinomial logistic regression analysis with stepwise variable selection to identify severity predictors for in-hospital mortality. Results: Two hundred sixty-two patients with a median age of 75.9 years (IQR 64.8–82.8) years were included for analysis. TG13/TG18 diagnostic criteria were more sensitive than TG07 diagnostic criteria (85.1 vs. 75.2%; p < 0.006). The majority of the patients (n = 178; 67.9%) presented with abdominal pain, pyrexia (n = 156; 59.5%), and vomiting (n = 123; 46.9%). Blood cultures were positive in 95 (36.3%) patients, and 79 (83.2%) patients had monomicrobial growth. The 30-day, 90-day, and in-hospital mortality numbers were 3 (1.1%), 11 (4.2%), and 15 (5.7%), respectively. In multivariate analysis, type 2 diabetes mellitus (OR = 12.531; 95% CI 0.354–116.015; p = 0.026), systolic blood pressure <100 mm Hg (OR = 10.108; 95% CI 1.094–93.395; p = 0.041), Glasgow coma score <15 (OR = 38.16; 95% CI 1.804–807.191; p = 0.019), and malignancy (OR = 14.135; 95% CI 1.017–196.394; p = 0.049) predicted in-hospital mortality. Conclusion: TG13/18 diagnostic criteria are more sensitive than TG07 diagnostic criteria. Type 2 diabetes mellitus, systolic blood pressure <100 mm Hg, Glasgow coma score <15, and malignant etiology predict in-hospital mortality in patients with AC. These predictors could be considered in acute stratification and treatment of patients with AC.

Kai Siang Chan, Sameer Padmakumar Junnarkar, Bei Wang, Yen Pin Tan, Jee Keem Low, Cheong Wei Terence Huey, Vishalkumar Girishchandra Shelat. Ann Hepatobiliary Pancreat Surg 2022;26:375-85. https://doi.org/10.14701/ahbps.22-028

Right portal vein ligation (PVL) has its recognized role in inducing hypertrophy of future liver remnant (FLR) prior to major liver resection. The aim of this study was to evaluate the safety, feasibility, and effectiveness of laparoscopic right PVL and to explore its applications. Laparoscopic right PVL was employed either during staging laparoscopy when a right hepatic trisectionectomy was indicated, leaving a small (<25%) FLR (indication 1), or during a laparoscopic left hepatic lobectomy (left lateral sectionectomy) when a second-stage right hemihepatectomy was to follow (indication 2). A follow up cross-sectional liver imaging was performed 4-6 weeks later with liver volumetry to confirm hypertrophy of the FLR before proceeding to major hepatectomy. Six patients (female, 5), 74-83 years old, underwent a laparoscopic right PVL, of whom 4 patients fulfilled indication 1 while 2 patients fulfilled indication 2. The median operating time for indication 1 was 60 minutes. There were no intra- or postoperative complications, and all procedures were completed laparoscopically. Repeat imaging of the liver demonstrated a median (range) hypertrophy of FLR of 24.5% (range, 20.7-33.1%). The right liver experienced atrophy. In the hands of the experienced laparoscopic hepatobiliary surgeon, laparoscopic right PVL is feasible and safe, and induces adequate regeneration of the FLR. Laparoscopic right PVL has its applications at the time of staging laparoscopy in patients requiring a right hepatic trisectionectomy in the presence of a small FLR and as part of a staged liver resection in patients with bilobar liver disease that spares segments 1 and 4.