Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

<i>Sinomenium</i> Inhibits the Viability of Hepatoma Carcinoma Cells through Activating IFNA2

Hepatocellular carcinoma (HCC) ranks the sixth place of most common cancers. Meanwhile, it is the tertiary mortality cause of cancer. There is no effective therapeutic method to prevent and treat the liver cancer. Sinomenine is a kind of Chinese traditional medicine herbal, it is reported that it can inhibit the viability of several cancer cells. The study is to explore whether sinomenine is also able to inhibit the cell viability of HCC and its potential mechanism. The IC50 of sinomenine in BEL-7402 cells was 5.351 mmol/L, and the IC50 of sinomenine in SMMC-7721 cells was 6.204 mmol/L. The gene expression results showed the relative expression of FGF2, CCND2, DCN, F3, MMP7, NRG1, HMGB1, TRIM29, HAS2, EHF, CTGF, PLK2 were down-regulated, and the relative expression of VEGF A, CITED2, NUPR1, DDX58, IRF9, NAMPT, MMP1, NDRG1, HMGA2, PPARGC1A, IFIT2, PARP9, HEY1, LOX, ETV1, ISG15, BACH, CYLD were up-regulated. Moreover, the IPA analysis results suggested that IFIT3, IFIT1, OAS1, MX1, IRF9, IFI6, IFITM1, ISG15 were up-regulated in BEL-7402 cells treated with sinomenine by activating IFNA2. The findings presented in this study may provide a promising method for the prevention and treatment of liver cancer.     

Clinicopathologic significance of LAIR-1 expression in hepatocellular carcinoma

Aim

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune inhibitory receptor which is expressed within most types of hematopoietic cells and negatively regulates immune responses. Recently, we found LAIR-1 expression to be present within tumors of nonhematopoietic lineages. However, the roles of LAIR-1 in hepatocellular carcinoma (HCC) have yet to be examined. The purpose of this study was to investigate the expression of LAIR-1 in HCC tissue and assess its clinical significance at this site.

Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

胃癌前哨淋巴结临床意义的研究

目的 观察胃癌前哨淋巴结的分布，探讨其临床意义。方法 回顾性分析288例胃癌前哨淋巴结术中染色后显影的范围及特征。术中向肿瘤边缘的正常胃壁浆膜下肌层、黏膜下层注射亚甲蓝，观察淋巴结显影的情况；切取各站淋巴结行病理检查。结果 288例胃癌术后病理诊断为T1期102例，T2期126例，T3期60例。术中成功显影270例，阳性率为93．8％。102例患者有淋巴结转移，其中前哨淋巴结（SNs）与非前哨淋巴结（non—SNs）均有转移者66例，仅前哨淋巴结有转移者18例，仅非前哨淋巴结有转移者18例。结论 通过前哨淋巴结，术中能准确预测胃癌淋巴结转移状况。在手术治疗淋巴结转移阴性的胃癌患者中，前哨淋巴结术中标识有望免除常规淋巴清扫。     

肱骨骨不连的手术治疗

目的探讨肱骨骨不连的手术治疗方法及疗效。方法1998年12月～2005年5月共收治肱骨骨不连患者25例,均为肱骨骨折内固定术后发生骨不连,其中3例并发骨髓炎,6例合并不同程度肱骨骨缺损,骨缺损长度为3～6cm。骨不连病程8个月～5年。15例行吻合血管游离腓骨移植,10例采用加压交锁髓内针进行肱骨固定并辅以自体骨植骨。结果术后25例均得到随访,时间6个月～6年2个月。吻合血管游离腓骨移植组中移植的腓骨段均与肱骨干形成骨性愈合,平均骨性愈合时间为3．1个月；交锁髓内针组平均骨愈合时间为3．8个月。按Crates和Whittle肩肘关节功能评价标准,腓骨移植组：优9例,良4例,差2例；交锁髓内针组：优5例,良3例,差2例。结论应用加压交锁髓内针辅以自体骨移植对硬化性肱骨骨不连是一种有效的外科治疗方法；对合并骨髓炎、大段骨缺损及严重骨质疏松的肱骨骨不连,采用吻合血管游离腓骨移植可一期进行修复与重建。