eGastroenterology最新文献

Background: The role of adjuvant transarterial chemoembolisation (TACE) to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma (HCC). Personalised predictive tool to select which patients may benefit from adjuvant TACE is lacking. This study aimed to develop and validate an online calculator for estimating the reduced risk of early recurrence from adjuvant TACE for patients with HCC.

Methods: From a multi-institutional database, 2590 eligible patients undergoing curative-intent hepatectomy for HCC were enrolled, and randomly assigned to the training and validation cohorts. Independent predictors of early recurrence within 1 year of surgery were identified in the training cohort, and subsequently used to construct a model and corresponding prediction calculator. The predictive performance of the model was validated using concordance indexes (C-indexes) and calibration curves, and compared with conventional HCC staging systems. The reduced risk of early recurrence when receiving adjuvant TACE was used to estimate the expected benefit from adjuvant TACE.

Results: The prediction model was developed by integrating eight factors that were independently associated with risk of early recurrence: alpha-fetoprotein level, maximum tumour size, tumour number, macrovascular and microvascular invasion, satellite nodules, resection margin and adjuvant TACE. The model demonstrated good calibration and discrimination in the training and validation cohorts (C-indexes: 0.799 and 0.778, respectively), and performed better among the whole cohort than four conventional HCC staging systems (C-indexes: 0.797 vs 0.562-0.673, all p<0.001). An online calculator was built to estimate the reduced risk of early recurrence from adjuvant TACE for patients with resected HCC.

Conclusions: The proposed calculator can be adopted to assist decision-making for clinicians and patients to determine which patients with resected HCC can significantly benefit from adjuvant TACE.

Primary liver cancers ranked as the sixth most commonly diagnosed cancers and the third-leading cause of cancer-related death in 2020. Despite encouraging findings on diagnosis and treatments, liver cancer remains a life-threatening disease with a still increasing incidence. Therefore, it is of interest to better characterise and understand the mechanistic process occurring at early steps of carcinogenesis. Inflammatory responses in liver diseases participate in the activation of liver progenitor cells (LPCs) facultative compartment but also to their transformation into cancer stem cells (CSCs) and give rise to primary liver cancer including hepatocellular carcinoma and cholangiocarcinoma. Higher intratumoural heterogeneity has been associated with poorer prognosis and linked to tumour escape from the immune surveillance and to resistance to chemotherapy. A better understanding of the malignant transformation of LPC as tumour initiating cells (ie, CSC) should also provide a potential new therapeutic target for anticancer therapy. In this review, we summarise the recent reports identifying underlying mechanisms by which chronic liver inflammatory responses could trigger the early steps in liver carcinogenesis, notably through the transformation of LPCs into tumour initiating cells.

Human gastrointestinal tract harbours trillions of microbes to form the gut microbiota. Through interacting with host cells, gut microbes play critical roles in host physiology and function. On the other hand, an altered or dysbiotic microbiota is now well acknowledged for contributing to cancer development and progression. Since the last decade, immunotherapy has risen as a promising and novel means to fight against cancer. Meanwhile, accumulating studies have clearly revealed the close association of gut microbiota with immunotherapy efficacy, suggesting the feasibility of modulating microbiota to improve treatment responsiveness. In this review, we present the current evidence elucidating the interplay between gut microbiota and immune system in the development of several cancers including colorectal cancer, hepatocellular carcinoma and melanoma. We also discuss how the gut microbiota impacts immune checkpoint inhibitors, one of the most common approaches of immunotherapy, and explore approaches that aim to harness the gut microbiota to improve treatment efficacy. Overall, investigations on the relationship between microbiota and cancer immunotherapy can have important clinical significance, potentially leading to the development of more potent and effective cancer therapeutics in the near future.

The structural and cellular organisation of the liver has unique features that define it as both a metabolic and an immunological organ. Noteworthy, liver resident macrophages, named Kupffer cells, represent the most frequent tissue resident macrophage population in the human body. Nonetheless, on acute or chronic tissue injury, Kupffer cells seem rather static and may undergo cell death, while the liver is massively infiltrated by circulating immune cells such as bone marrow-derived macrophages, also termed monocyte-derived macrophages, which drastically alter the hepatic immune landscape. Over the last decade, our knowledge on liver macrophage populations during homeostasis and liver diseases has greatly expanded. This particularly holds true in light of the recent fast-paced technological advances that brought novel dimensions to our knowledge, either in single-cell suspensions, in a two-dimensional plane or a three-dimensional space, or even in time-lapse (intravital) microscopy. This novel understanding goes from unravelling a previously underestimated macrophage diversity (eg, in terms of activation phenotype or cellular origins) to identifying spatially or temporally restricted responses that drive liver disease outcome. This review aims at providing insights into the most recent breakthroughs in our understanding of liver macrophage biology and its roles in liver (patho)physiology, in a four-dimensional perspective.

Cholera is one of the most rapidly fatal infectious diseases known. Historically, two major problems have been faced by those who care for patients with cholera: first, how to treat individual patients to prevent rapid death, and second, how to prevent the spread of this highly contagious disease in the immediate community and beyond. In this review, we will discuss how clinical scientists have approached these two issues with some personal experiences that Dr William B Greenough III encountered when he was addressing these problems and treating cholera victims at the Pakistan SEATO Cholera Research Laboratory in the early 1960s in Dhaka, East Pakistan.