A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

BACKGROUND: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).
METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023.
RESULTS: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date.
CONCLUSIONS: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.

Biliary tract cancers (BTCs) represent a spectrum of malignancies associated with a dismal prognosis. Recent genomic profiling studies have provided a deeper understanding of the complex and heterogenous molecular landscape of BTCs, identifying several actionable genetic alterations, and expanding treatment options. Due to the high number and complexity of genetic alterations which require testing, next-generation sequencing (NGS) is currently the preferred approach over conventional methods (i.e., immunohistochemistry, fluorescence in-situ hybridization and PCR) for molecular profiling of BTCs and should be performed upfront in all BTC patients. However, BTC sampling often yields low tumor cellularity tissue, hampering NGS analysis. Future perspectives to overcome this obstacle include liquid biopsy and optimization of biopsy protocols. In this position paper, the authors discuss the current histopathologic, molecular, and therapeutic landscape of BTCs, provide a critical overview of the available testing methods for molecular diagnostics, and propose a practical diagnostic algorithm for molecular testing of BTC samples.

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Intrahepatic cholangiocarcinoma (iCCA) develops inside the liver, between bile ductules and the second-order bile ducts. It is the second most frequent primary liver cancer after hepatocellular carcinoma, and its global incidence is increasing. It is associated with an alarming mortality rate owing to its silent presentation (often leading to late diagnosis), highly aggressive nature and resistance to treatment. Early diagnosis, molecular characterisation, accurate staging and personalised multidisciplinary treatments represent current challenges for researchers and physicians. Unfortunately, these challenges are beset by the high heterogeneity of iCCA at the clinical, genomic, epigenetic and molecular levels, very often precluding successful management. Nonetheless, in the last few years, progress has been made in molecular characterisation, surgical management, and targeted therapy. Recent advances together with the awareness that iCCA represents a distinct entity amongst the CCA family, led the ILCA and EASL governing boards to commission international experts to draft dedicated evidence-based guidelines for physicians involved in the diagnostic, prognostic, and therapeutic management of iCCA.

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define \"related stricture\" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.
【更新要点】： 自2010年至今指南有哪些新内容？A.纳入原发性和非原发性硬化性胆管炎（primary sclerosing cholangitis，PSC）患者的胆管癌的诊断和管理指引。B.引入术语相关狭窄一词，定义为与梗阻性胆汁淤积和/或细菌性胆管炎的体征或症状相关的任何胆总管或肝管的胆道狭窄。C.对于磁共振成像和胰胆管造影结果不明确的患者，出于诊断目的，应复查高质量的磁共振成像/胰胆管造影。应避免为了诊断PSC进行内镜逆行胰胆管造影。D.对于未知炎症性肠病（inflammatory bowel disease，IBD）的PSC患者，应进行诊断性结肠镜组织学取样检查，每5年复查1次，直至检测到IBD。E.对于合并IBD的PSC患者，应从15岁开始进行结肠癌监测。F.PSC的临床风险新工具可用于风险分层，但应谨慎解释个体发生率。G.所有PSC患者应考虑参与临床试验；然而，如果熊去氧胆酸（13~23 mg·kg(-1)·d(-1)）耐受良好，且在治疗12个月后碱性磷酸酶(儿童中的γ-谷氨酰转移酶)和/或症状有显著改善，则可以考虑继续使用。H.所有疑似肝门部或远端胆管癌的患者均应进行内镜逆行胰胆管造影胆道细胞学刷检和荧光原位杂交分析。I.除了PSC和复发性胆管炎的患者，终末期肝病模型标准有统一的网络器官共享新政策。对于不可切除的肝门部胆管癌，直径< 3 cm或合并PSC且无肝内(外)转移的患者，建议新辅助治疗后进行肝移植。.

暂无摘要。

肝内胆管系统是由衬覆的胆管上皮细胞及其所属胆管周腺体所构成，经逐级分支形成大胆管群（区胆管-段胆管）和小胆管群（赫令管-小叶间胆管-隔胆管），据此可将肝内胆管癌（intrahepatic cholangiocarcinoma，ICC）相应地分为大胆管型和小胆管型以及细胆管癌和伴胆管板畸形型等特殊组织学亚型。由于不同组织学亚型的ICC在细胞形态、组织结构、生长方式、侵袭行为、免疫表型、分子变异以及临床预后等方面既有差异，又有重叠，因而ICC的组织学分型是常规病理诊断中的重点和难点。为此，《肝内胆管癌病理诊断专家共识（2022版）》编写专家委员会在第5版WHO消化系统肿瘤分类的基础上，针对组织学分型诊断标准、免疫组织化学谱组合策略、需要鉴别诊断的变异类型、治疗性靶点的分子检测以及病理诊断报告要点等问题，提出了9条推荐建议，以期为ICC的规范化和精细化病理分型诊断提供参考。.

The updated German S3 guideline \"Diagnostics and therapy of hepatocellular carcinoma and biliary carcinomas\" covers two tumor entities. The original guideline published in 2013 focusing only on the diagnosis and therapy of hepatocellular carcinoma (HCC) has been expanded to include intrahepatic cholangiocarcinoma. These guidelines were developed within the framework of the guideline program on oncology of the Scientific Medical Society e. V. (AWMF), the German Cancer Society (DKG) and German Cancer Aid Society (DKG) under the auspices of the German Society for Digestive and Metabolic Diseases (DGVS). In addition to updated recommendations regarding histopathology, radiological diagnostics and treatments, the main innovations of the revised guidelines on HCC include a complete revision of the section on the systemic therapeutic approach in advanced stages of the disease. This article presents the significance of the current recommendations for diagnostic and interventional radiology in comparison to other national and international guidelines and should serve to improve the quality of patient care through more widespread dissemination.
UNASSIGNED: Die aktualisierte deutsche S3-Leitlinie „Diagnostik und Therapie des hepatozellulären Karzinoms und biliärer Karzinome“ umfasst zwei Tumorentitäten. Bisher bestand nur eine Leitlinie zur Diagnostik und Therapie des hepatozellulären Karzinoms (HCC) aus dem Jahr 2013, wobei die Leitlinie zum Cholangiokarzinom (CC) jetzt zum ersten Mal bearbeitet wurde. Diese Leitlinien entstanden im Rahmen des Leitlinienprogramms Onkologie der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), der Deutschen Krebsgesellschaft e. V. (DKG) und Deutschen Krebshilfe unter Federführung der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS). Die wesentlichen Neuerungen der überarbeiteten Leitlinien zum HCC umfassen neben aktualisierten Empfehlungen hinsichtlich Histopathologie, radiologischer Diagnostik und Therapien vor allem eine komplette Überarbeitung des Abschnitts zum systemtherapeutischen Vorgehen bei fortgeschrittenem Stadium der Erkrankung. Der vorliegende Artikel stellt die Bedeutung der aktuellen Empfehlungen für die diagnostische und interventionelle Radiologie im Vergleich zu anderen nationalen und internationalen Leitlinien dar und soll durch eine flächendeckendere Verbreitung der Qualitätssteigerung bei der Patientenversorgung dienen.