胎盘生长因子在肝内胆管癌中促进肿瘤黏连和治疗耐药性

正[据Gut 2021年1月报道]题:胎盘生长因子在肝内胆管癌中促进肿瘤粘连和治疗耐药性(作者Aoki S等)肝内胆管癌(ICC)是一种罕见的肝脏恶性肿瘤,治疗方法有限,其特征为侵袭性进展、纤维增生和血管异常。本研究目的是确定胎盘生长因子(PIGF)在ICC进展中的作用。     

《2014年美国肝胆胰学会共识声明:肝内胆管癌管理》摘译

<正>本文介绍了2014年美国肝胆胰学会(American HepatoPancreato-Biliary Association,AHPBA)的肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)诊治的专家共识,内容覆盖了其诊断、分期、外科治疗、辅助治疗等多方面内容,可为临床实践提供依据。1 ICC的诊断与分期1.1临床表现ICC患者早期多无临床表现,进展阶段可出     

肝胆管结石进展肝内胆管癌的危险因素研究

目的 探讨肝胆管结石进展为肝内胆管癌(ICC)的危险因素。方法 纳入我院2017年11月—2019年11月宿州市第一人民医院收治的肝胆管结石患者150例,收集患者的临床资料,根据其是否进展为ICC,分为ICC组、非ICC组。比较两组临床特征,经logistic回归模型分析肝胆管结石进展为ICC的多因素。结果 在纳入的150例患者中,39例(26.00%)进展为ICC,111例(74.00%)未进展为ICC。ICC组胆肠吻合术史、肝硬化、肝胆管结石病程≥10年、糖尿病占比显著高于非ICC组,而结石彻底清除占比显著低于非ICC组(P0.05)。Logistic回归模型显示,胆肠吻合术史、肝硬化、肝胆管结石病程≥10年、糖尿病是肝胆管结石进展为ICC的危险因素(P0.05),结石彻底清除是预防其进展为ICC的保护性因素(P0.05)。结论 肝胆管结石进展为ICC与多种因素有关,主要包括胆肠吻合术史、肝硬化、肝胆管结石病程、糖尿病,而彻底清除结石能降低ICC发生风险。     

Cajal间质细胞与胃肠动力关系的研究进展

Cajal间质细胞(interstitial cells of Cajal,ICC)是胃肠慢波的起搏细胞,具有产生慢波、传导慢波电位、调节神经递质等功能,是调节胃肠动力的重要环节。ICC在维持正常胃肠动力方面发挥着重要作用,同时其形态、数量及分布的改变会导致多种胃肠动力障碍性疾病。一些以ICC为靶向治疗胃肠动力性疾病药物的研究也取得一定进展。本文就近年来ICC与胃肠动力关系的研究进展作一概述。     

肝内胆管癌的危险因素与发病机制

肝内胆管癌(ICC)病因复杂,高度侵袭、预后不良,是仅次于肝细胞癌的第二大肝胆恶性肿瘤。早期手术切除仍是ICC的最佳治疗方案,但因其起病隐匿,恶性程度高,多数患者就诊时已处于中晚期,失去了最佳的手术时机。因此,临床上能够对ICC进行早期及时的识别和干预十分重要。目前已经有研究证实了原发性硬化性胆管炎、病毒性肝炎、肝内胆管结石等危险因素与ICC的密切关系,分子生物学和遗传学技术的迅速发展也为ICC发病机制的深入研究提供了更好的方法。现将近年来ICC的危险因素及发病机制相关研究作一综述,以期为其临床早期诊治提供更多有价值的信息。     

肝内胆管细胞癌诊断及治疗的现状与挑战

肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)是一类起源于肝内胆管上皮细胞的恶性肿瘤。ICC发病较隐匿,早期无明显的临床症状,临床上尚缺少特异度高的早期筛查诊断标志物,很多患者在发现时已进展到中晚期,失去采取根治性切除术治疗的机会;即使手术切除,复发及转移等诸多因素也会导致ICC患者病死率高、远期生存预后差的局面。国际上尚无成熟的ICC个体化精准治疗推荐策略,现有的分期及预后模型主要基于手术切除的患者所创建,缺少普适性,临床应用受限。因此提高ICC患者早期确诊率、制定精准的治疗策略、探索预后风险因素是临床改善生存结局的途径。本文结合ICC研究进展,分析了ICC的诊断和治疗现状以及面临的挑战。     

Cajal间质细胞在胃肠动力障碍性疾病中的研究

胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)较为常见,但发病机制尚不明确。Cajal间质细胞(interstitial cells of Cajal,ICC)是胃肠道慢波运动的起搏细胞、调控者和感受器,其病理性改变可导致DGIM的发生。ICC的重要生理功能使其有望成为DGIM的治疗新靶点。本文就ICC的研究认识及其在DGIM中作用的相关研究作一概述。     

Cajal间质细胞与炎症性肠病关系的研究进展

Cajal间质细胞(ICC)主要分布在消化道平滑肌细胞与神经细胞之间,通常认为ICC是参与产生和传播消化道慢波的起搏细胞,并可通过传递和调节神经递质来调节胃肠道的活动,与肠道炎性反应的病理生理有关。炎症性肠病(IBD)是一种慢性非特异性炎性疾病,治疗困难,易复发,其病因和发病机制尚不明确。该文综述了ICC与IBD发生、发展的关系,旨在为探究IBD的发病机制及治疗方式提供新的思路。     

从肿瘤异质性看肝内胆管癌的细胞起源

肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)约占肝脏原发肿瘤的5%-15%,仅次于肝细胞肝癌,其发病率逐年上升.由于ICC发病因素、地域分布、临床表现、生物学特性等存在明显的异质性,且缺乏有效治疗手段,预后极差.长久以来,人们一直认为ICC来源于胆管二级及以上分支的上皮细胞.伴随分子生物学技术的发展,人们对ICC的认识正在发生质的变化.现阶段发现ICC的细胞起源呈多元化,包括肝细胞、发育异常或未成熟的胆管上皮细胞,多能干细胞(肝干/前体细胞)或管周腺体细胞.因此,我们推断ICC的异质性可能与不同的细胞起源有关.     

胆管细胞型肝癌的诊治研究进展

<正>目前原发性肝癌占我国恶性肿瘤发病率第4位,占死亡率第2位~([1])。原发性肝癌(PLC)以肝细胞癌(HCC)为主,胆管细胞型肝癌(ICC)占PLC的5%~25%。ICC是由肝内胆管被覆上皮发生的一种原发性肝癌,起源于二级以上的肝内胆管上皮恶性肿瘤~([2])。本病症状隐匿,早期难以发现,根治性切除机会较少,进展快,预后差,本文试对其诊治的研究进展作一概述。一、病因及相关危险因素1.肝内胆管结石病ICC与肝胆管结石的关系密切。在肝胆管结石高发地区(如东亚地区),ICC发病率也偏高。国外报道肝内胆管结石并发ICC的发病率为2%~     

Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.     

Surgical treatment of intrahepatic cholangiocarcinoma in the USA

Cholangiocarcinoma (CC) is a malignancy that arises from the epithelial cells of the biliary system (ductules as well as large ducts, and likely from progenitor cells, as well). Intrahepatic CC (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), and accounts for 10–15% of primary liver cancers. ICC differs from both extrahepatic and CC and HCC and has unique risk factors, histological features, genetic alterations and clinical outcomes. The natural history and results of surgical intervention are not well described as ICC is a relatively uncommon tumor, especially in the USA. This article reviews the literature relevant to the surgical management and outcome of patients with ICC in the USA.     

Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma

Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized.     

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.     

Biology of hepatic cancer stem cells

Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver and is the third most frequent cause of cancer death worldwide. Although advances in HCC detection and treatment have increased the likelihood of a cure at early stages of the disease, HCC remains largely incurable because of late presentation and tumor recurrence. Only 25% of HCC patients are deemed suitable for curative treatment, with the overall survival at just a few months for inoperable patients. Additionally, this disease is particularly difficult to treat because of the high recurrence rate, its chemotherapy-resistant nature and the premalignant nature of surrounding cirrhotic liver disease. In the past few years, compelling evidence has emerged in support of the hierarchic cancer stem cell (CSC)/tumor-initiating cell (T-IC) model for solid tumors, including HCC. Understanding the characteristics and function of CSCs in the liver has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress in liver CSC research with regard to identification, regulation and therapeutic implications will be discussed.     

Liver transplantation for intrahepatic cholangiocarcinoma

The indication of liver transplantation for intrahepatic cholangiocarcinoma (ICC) is highly controversial. Initially, liver transplantation was embraced as a promising treatment for ICC, providing both a wider surgical margin and a potential cure for the underlying liver disease. However, the majority of transplant centers have abandoned liver transplantation for ICC due to poor long‐term survival and high recurrence rates. Interestingly, these decisions were based on studies with highly inconsistent outcomes due to a limited number of patients, various patient selection criteria, and the use of nonstandardized adjunctive therapy protocols. Indeed, recent studies have revealed that ICC patients with small solitary tumors have excellent long‐term survival after liver transplantation. Moreover, as seen in early‐stage hilar cholangiocarcinoma, neoadjuvant and adjuvant therapy hold promise for improved long‐term survival in patients with locally advanced ICC. As we work to expand treatment options for ICC, further evidence of success in this area is needed in order to justify the use of limited organ resources to treat ICC. Continued efforts to improve diagnosis of ICC, hone patient selection criteria, and implement standardized treatment protocols could provide certain patients with ICC access to potentially life‐saving liver transplantation.     

Right trisectionectomy of the liver for intrahepatic cholangiocarcinoma with bile duct invasion in a Jehovah's Witness

Intrahepatic cholangiocarcinoma (ICC) is well known to have a very poor prognosis. Aggressive surgical strategies in the treatment of ICC, including major hepatectomy, have been reported to afford patients the best chance for significant survival. Recent advancements in surgical techniques concerning live donor liver transplantation have dramatically improved the results of major hepatectomy. However, surgical treatment of biliary malignancy is complex and is known to increase the likelihood of blood transfusion. We describe a Jehovah's Witness patient with ICC and concomitant bile duct invasion who had a successful right trisectionectomy with bile duct resection, lymph node dissection, and Rouxen-Y hepatico-jejunostomy without blood transfusion. A multidisciplinary preparation was crucial in obtaining this positive outcome. Importantly, bloodless liver transection techniques with inflow clamping, meticulous dissection, and hemostasis should be utilized for major hepatectomy in a Jehovah's Witness. The success of this case may alert clinicians to consider a hepatectomy as a possible option in the treatment of ICC in a Jehovah's Witness.     

Report of the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan.

In the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan, 18 213 individuals were newly registered as patients with primary liver cancer at 645 medical institutions over a period of 2 years (from 1 January 2002 to 31 December 2003). Of these patients, 94.2% had hepatocellular carcinoma (HCC) and 4.1% had intrahepatic cholangiocarcinoma (ICC). In addition, 24 705 follow-up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients, and the cumulative survival rates of newly registered patients in the 12th to 17th follow-up surveys conducted between 1992 and 2003 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The data obtained in this follow-up survey should contribute to future research and medical practice for primary liver cancer.     

Hepatocellular carcinoma - from immunobiology to immunotherapy

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide with an increasing incidence. The clinical outcome is influenced by the underlying liver cirrhosis, the size of the tumour at the time of diagnosis and the few therapeutic options currently available. In recent years there has been a lot of progress in the understanding of HCC immunobiology. This review summarizes our current knowledge of HCC biology, the role of chronic inflammation in carcinogenesis and the role of tumour-specific immune responses. Furthermore, we will present potentially new, immune-based therapies that might open up new avenues for the treatment of HCC.     

Current status of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma （ICC） is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.