Biliary tract cancers, including gallbladder, intrahepatic and extrahepatic bile duct cancers, have a high mortality rate, with data showing that about 10,000 people were diagnosed with gallbladder or bile duct cancer in the United States in 2014, with more than 3,000 deaths annually. The 2015 NCCN Clinical Practice Guidelines for Biliary Tract Cancer (hereinafter referred to as the “new guidelines”) developed by the National Comprehensive Cancer Network (NCCN) are clinical recommendations based on the latest, high-quality evidence-based medical research and expert consensus. The 2015 NCCN Clinical Practice Guidelines for Biliary Tract Cancer (“the new guidelines”) are clinical recommendations based on the latest, high-quality evidence-based research and expert consensus, with the goal of improving treatment effectiveness and efficiency. Compared with the second edition of the 2014 guidelines (hereinafter referred to as the “Guidelines”), the “New Guidelines” have added and improved various aspects of gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma. This article introduces the content of the new version of the Guidelines and explains the key points of the updates. Gallbladder cancer is the most common and aggressive biliary tract tumor, mostly adenocarcinoma, and its incidence rate increases with age. Gallbladder cancer is usually confined, easily invades blood vessels, and is prone to local or extensive lymph node metastasis and distant metastasis. Compared with hilar cholangiocarcinoma, patients with gallbladder cancer have a shorter median survival time, are prone to recurrence, and have a shorter survival time after recurrence. 2015 NCCN clinical practice guidelines on gallbladder cancer include the following aspects. 1.1 Incidental detection of gallbladder cancer during cholecystectomy Patients with gallbladder cancer have non-specific clinical symptoms; therefore, it is often detected intraoperatively when other gallbladder diseases are suspected and cholecystectomy is performed. In this regard, the “new guidelines” suggest that the stage of gallbladder cancer should be determined first. If the operator’s expertise is not sufficient, he should collect relevant clinical evidence and refer to a more advanced treatment center; if intraoperative clinical evidence confirms cancer, an extended cholecystectomy should be considered if expertise permits; if intraoperative suspicion of an occupying lesion is present, biopsy is not recommended because it may lead to peritoneal dissemination; if resectability is unknown, the procedure should be terminated and postoperative imaging should be combined with CT, MRI and chest CT of the gallbladder to assess the possibility of surgery: (1) for patients who can be treated surgically, cholecystectomy, hepatic segmental resection, lymph node dissection with or without bile duct resection to ensure negative margins, combined with postoperative adjuvant therapy and monitoring; (2) for patients who cannot be treated surgically, a combination of gemcitabine and cisplatin chemotherapy, fluorouracil- or gemcitabine-based chemotherapy, fluorouracil-based radiotherapy, clinical trials, and supportive care. 1.2 Gallbladder cancer found on pathological examination after cholecystectomy Pathological examination should be routinely performed after cholecystectomy for reasons such as gallbladder polyps and gallbladder adenomas. For gallbladder cancer unexpectedly found on pathological examination, the surgeon should review the details of the operation and recall the integrity of the cholecystectomy, any signs of metastasis, the location of the lesion, and other relevant information. If the pathology report indicates that the gallbladder cancer is stage T1a and the surgical margins are negative, the “new guideline” recommends observation because the data shows that the long-term survival rate of cholecystectomy alone is 100% when the margins are negative, and the “new guideline” recommends that on the basis of observation Adjuvant treatment can be considered on the basis of observation. For gallbladder cancer with pathological examination report suggesting stage T1b or above, the “new guideline” recommends the next step of treatment after evaluating the possibility of surgery in combination with imaging examination. Patients with operable disease should be considered for hepatic segmental resection, lymph node dissection with or without bile duct resection, and postoperative adjuvant therapy and monitoring. “The new guidelines emphasize that distant lymph node metastases should be excluded prior to resection, as this is a contraindication to further resection; in addition, data show that patients with stage T1b, T2, or T3 gallbladder cancer often have residual lesions in the liver or common bile duct, and extended surgery may be considered to ensure negative margins. For inoperable patients, combination chemotherapy with gemcitabine and cisplatin, fluorouracil or gemcitabine-based chemotherapy, fluorouracil chemoradiotherapy, clinical trials and supportive care are available. 1.3 Patients with imaging findings of an occupying gallbladder lesion are recommended to undergo an immediate multidisciplinary evaluation to discuss the possibility of surgery: (1) in operable patients, definitive resection without biopsy, cholecystectomy, hepatic segmental resection, lymph node (1) Immediate definitive resection without biopsy, cholecystectomy, hepatic segmental resection, lymph node dissection with or without choledochotomy, combined with postoperative adjuvant therapy and monitoring. “The new guidelines emphasize that in some cases with an inexact diagnosis, cholecystectomy can be performed with intraoperative pathological examination of frozen sections, and radical surgery can be performed immediately after the cancer is confirmed. (2) For inoperable patients, combination chemotherapy with gemcitabine and cisplatin, fluorouracil or gemcitabine-based chemotherapy, fluorouracil chemoradiotherapy, clinical trials and supportive therapy are available. 1.4 Gallbladder cancer with jaundice as the first symptom The appearance of jaundice is a sign of poor prognosis of gallbladder cancer, often indicates advanced disease with low survival rate, and therefore is a relative contraindication to surgical treatment. However, some studies have suggested that surgical treatment has some prognostic benefit for a small proportion of patients with lymph node-negative jaundice. In patients with jaundice, if gallbladder cancer is suspected, surgery must be performed for curative purposes. “The new guidelines recommend a multidisciplinary consultation to assess the possibility of surgery, which should include cholangiography to determine the extent of tumor invasion of the hepatobiliary system, with non-invasive magnetic resonance cholangiography (MRCP) preferred, followed by ERCP or percutaneous transhepatic cholangiography (PTC). For operable patients, the “new guideline” adds preoperative consideration of biliary drainage, cholecystectomy, hepatic segmental resection, lymph node dissection with or without choledochotomy, and postoperative combination of adjuvant therapy and monitoring. The new guidelines emphasize that gallbladder cancer with jaundice usually indicates a poor prognosis and requires careful surgical evaluation. “The new guidelines recommend that inoperable patients have biliary drainage before starting chemotherapy, and that chemotherapy regimens include a combination of gemcitabine and cisplatin, fluorouracil or gemcitabine-based chemotherapy, fluorouracil chemoradiotherapy, clinical trials and supportive care. Preoperative surgical establishment of a biliary drainage bypass or percutaneous percutaneous drainage can not only significantly improve the manifestations of biliary obstruction such as jaundice, but also improve the patient’s immune function. The biliary drainage site should depend on the location of the tumor. The establishment of biliary drainage bypass should ensure that the bile-intestinal anastomosis is as far away from the tumor site as possible to avoid tumor invasion and blockage of the anastomosis leading to the recurrence of jaundice, and distal bile duct cancer can be selected from the gallbladder, upper bile duct or hilar bile duct with jejunostomy. When the indications are met, percutaneous hepatic puncture for bile duct drainage is a good choice. 1.5 Metastatic gallbladder cancer Metastasis includes distant metastasis, metastasis to lymph nodes in the hilar region, jaundice or vascular invasion with involvement of the hilar region. In these patients, preoperative evaluation and biopsy may be a priority, and the “new guidelines” recommend biliary drainage, combination chemotherapy with gemcitabine and cisplatin, fluorouracil- or gemcitabine-based chemotherapy, clinical trials, and supportive care. The literature reports that biliary drainage is an appropriate pre-chemotherapy treatment and that chemotherapy after biliary drainage can improve patient survival. 1.6 Adjuvant therapy and monitoring after surgical treatment of gallbladder cancer The optimal adjuvant treatment strategy for patients after radical surgery has not been defined and clinical data supporting standard treatment are lacking. A multivariate Cox proportional risk model analysis found that adjuvant therapy in patients with stage T2 or higher could be beneficial for survival. Therefore, the “new guidelines” recommend postoperative fluorouracil chemoradiotherapy, fluorouracil or gemcitabine chemotherapy, and monitoring for changes in disease. Studies have shown that patients with gallbladder cancer, especially those with positive lymph nodes, can benefit from adjuvant chemotherapy or chemoradiotherapy. Among them, gemcitabine in combination with cisplatin is considered to be the first-line agent for advanced bile duct cancer. The “new guidelines” suggest that postoperative patients with gallbladder cancer should insist on imaging every 6 months for 2 years, and if recurrence occurs, treatment should be directed according to the aforementioned “new guidelines”. Cholangiocarcinoma includes all tumors derived from bile duct epithelial cells, >90% of which are adenocarcinoma, and can be divided into intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma according to the anatomical location. Intrahepatic cholangiocarcinoma is located in the liver parenchyma, while extrahepatic cholangiocarcinoma includes hilar cholangiocarcinoma (also known as Klatskin’s tumor) originating at or near the union of the left and right hepatic ducts and distal extrahepatic cholangiocarcinoma originating from the extrahepatic bile ducts in the upper biliopancreatic jugular. Extrahepatic bile duct cancer is more common than intrahepatic bile duct cancer, and hilar bile duct cancer is the most common extrahepatic bile duct cancer. 2.1 Intrahepatic cholangiocarcinoma Patients with intrahepatic cholangiocarcinoma have non-specific clinical manifestations and usually do not show symptoms of bile duct obstruction, but are often detected incidentally by isolated masses on the liver on imaging. Although most patients are diagnosed at advanced stages of the disease and are not suitable for surgery, complete resection is still the only curative means for patients with intrahepatic cholangiocarcinoma. For isolated intrahepatic masses, if imaging is consistent with adenocarcinoma, the Guidelines recommend immediate multidisciplinary evaluation to determine the possibility of surgery: (1) For operable patients, preoperative evaluation should be performed for the presence of multiple hepatic foci, lymph node metastases or distant metastases, as lymph node metastases and distant metastases beyond the hilar region are contraindications to surgical The presence of multiple liver lesions, lymph node metastases or distant metastases should be evaluated preoperatively because lymph node metastases beyond the hilar region and distant metastases are contraindications to surgical resection. The surgical option is partial hepatectomy, usually a major hepatectomy, but wedge resection, segmental resection and enlargement of the liver can be considered as long as negative margins can be met. “The new guidelines emphasize that lymph node dissection in the hilar region is reasonable because it not only provides information on the staging of cholangiocarcinoma, but also allows for some assessment of prognosis. However, lymph node metastasis to the porta hepatis usually indicates a poor prognosis, and resection must be performed in highly specific patients. Patients should receive postoperative adjuvant therapy and be monitored for changes in their condition. (2) For inoperable patients, combination chemotherapy with gemcitabine and cisplatin, clinical trials, fluorouracil or gemcitabine-based chemotherapy, fluorouracil chemoradiotherapy, local therapy and supportive therapy are available. Compared to the old “guidelines”, the “new guidelines” state that intra-arterial chemotherapy is now available as a clinical trial. (3) Patients with metastases are treated in the same way as inoperable patients. According to the literature, the tumor size of intrahepatic cholangiocarcinoma has no significant effect on postoperative survival rate. The factors that have significance are the number of tumors, vascular invasion and the status of lymph nodes, and the number of tumors and vascular invasion only have significant guiding significance at N0. In the latest revision of the 7th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma, tumor number, vascular invasion, and lymph node metastasis are included as staging factors, which will help guide the prognosis of patients with intrahepatic cholangiocarcinoma. In addition, Chaiteerakij et al. of Mayo Clinic recently proposed a new staging method and published it in American Journal of Gastroenterology, which combines ECOG activity status score, tumor size and number, lymph node metastasis and peritoneal metastasis and CA19-9 level, and has good ability to differentiate patients’ survival. It has good differentiation ability and can better infer the prognosis. “The new version of the guidelines classifies patients into 3 categories according to their postoperative liver condition. (1) Patients without local residual lesions: The new guidelines recommend observation, clinical trials and fluorouracil- or gemcitabine-based chemotherapy, with imaging every 6 months for 2 years. (2) Patients with positive microscopic margins or positive local lymph nodes: The new guidelines recommend fluorouracil chemoradiotherapy or fluorouracil- or gemcitabine-based chemotherapy, with imaging every six months for two years. (3) Patients with residual localized lesions: The new guidelines recommend combination chemotherapy with gemcitabine and cisplatin, clinical trials, fluorouracil- or gemcitabine-based chemotherapy, local therapy, and supportive therapy. “The new guidelines state that not only intra-arterial chemotherapy but also systemic chemotherapy can be considered in clinical trials. 2.2 Extrahepatic cholangiocarcinoma Patients with extrahepatic cholangiocarcinoma often present with symptoms of bile duct obstruction such as jaundice, pain, and abnormal liver function, followed by abnormal lesions found in imaging studies. The radical treatment for extrahepatic cholangiocarcinoma is complete resection of the lesion with negative margins. In the literature, the 5-year survival rates of radical resection for hilar cholangiocarcinoma and distal cholangiocarcinoma are 20% to 40% and 16% to 52%, respectively. When the above clinical manifestations occur, the “new guidelines” recommend immediate multidisciplinary evaluation to determine whether surgery is possible: (1) For inoperable patients, the “new guidelines” recommend bile duct drainage and referral to a transplantation center if the patient is suitable for transplantation. (1) For inoperable patients, the “new guidelines” recommend bile duct drainage, referral to a transplant center if appropriate for transplantation, puncture biopsy if not, followed by gemcitabine and cisplatin combination chemotherapy, clinical trials, fluorouracil or gemcitabine-based chemotherapy, fluorouracil chemoradiotherapy and supportive therapy. (2) For patients who can be operated, preoperative application of laparoscopy can be considered to determine the staging and biliary drainage, and those found unresectable after intraoperative exploration are treated as above, and those who can be resected are treated surgically, followed by postoperative adjuvant therapy and monitoring. (3) For patients with metastasis, the “new guidelines” recommend biliary drainage by surgical bypass or endoscopy (e.g. ERCP) or percutaneous methods (e.g. PTC), and most patients often undergo biliary stenting and biopsy at the same time. After the diagnosis of cholangiocarcinoma, patients are given gemcitabine and cisplatin combination chemotherapy, clinical trials, fluorouracil or gemcitabine based chemotherapy and supportive therapy. The basic principles of surgical treatment for extrahepatic cholangiocarcinoma are complete resection with negative margins and regional lymph node dissection, pancreaticoduodenectomy for distal cholangiocarcinoma, and resection of most of the liver for proximal cholangiocarcinoma. In rare cases, only the bile duct and regional lymph nodes can be removed for mid-stage tumors. “The new guidelines suggest that surgical treatment of hilar cholangiocarcinoma should take into account the following points: (1) The residual liver should have an intact arterial and venous supply and bile duct drainage after surgery. (2) Contraindications, i.e., liver metastases, peritoneal metastases, distal lymph node metastases beyond the hilar region, etc., should be excluded before starting exploration, and distal exploration should be considered only when resectability is confirmed. (3) Most of the liver on the involved side needs to be resected, and the lesion encircling the biliary confluence usually also needs to be resected with caudate lobes, and the portal vein, hepatic artery, and biliary system should be reconstructed after resection. It has been reported in the literature that enlarged resection can help improve survival and reduce the recurrence rate. (4) Surgical treatment should be accompanied by lymph node dissection in the porta hepatis. (5) Frozen pathology of the proximal and distal bile ducts is recommended if the operable area is large. (6) For patients with potentially small postoperative residual liver volume, bile duct drainage (ERCP or PTC) or portal vein embolization on one side is recommended prior to surgery. (7) For unspread locally advanced hilar cholangiocarcinoma, liver transplantation is the only possible cure, with a 5-year survival rate of 25%-42%. The surgical treatment of distal cholangiocarcinoma needs to be evaluated for distal metastasis, and surgery generally requires pancreaticoduodenectomy and local structural reconstruction. After surgical treatment, for patients with negative margins, negative regional lymph nodes or carcinoma in situ, the “new guideline” recommends observation, fluorouracil chemoradiotherapy, fluorouracil- or gemcitabine-based chemotherapy and clinical trials, with imaging every six months for two years; for patients with positive margins, residual foci in resected tissue and regional lymph nodes, the “new guideline” recommends observation, fluorouracil- or gemcitabine-based chemotherapy and clinical trials. For patients with positive margins, residual foci in resected tissue and positive regional lymph nodes, the “new guideline” recommends fluorouracil chemoradiotherapy followed by additional fluorouracil- or gemcitabine-based chemotherapy or fluorouracil- or gemcitabine-based chemotherapy for regional positive lymph nodes, with imaging every six months for two years. The prognosis of patients with biliary tract cancer is poor, and most patients are diagnosed at an advanced stage, and many treatment measures have emerged after long-term research. The “new version of the guidelines” suggests that (1) gemcitabine in combination with cisplatin can be the first-line chemotherapeutic agent for patients with advanced cholangiocarcinoma; (2) liver transplantation can be used as a treatment for unspread cholangiocarcinoma; (3) local treatment of the liver such as ablation and direct arterial therapy is suitable for unresectable or metastatic intrahepatic cholangiocarcinoma; (4) all (4) all patients with bile duct cancer should undergo pre-treatment evaluation, careful patient screening and active multidisciplinary collaboration are necessary to achieve treatment, and participation in prospective clinical trials is the best treatment approach regardless of the patient’s stage. The NCCN guidelines are a consensus reached by multidisciplinary experts in the United States based on clinical basis and treatment experience. 2015 NCCN clinical practice guidelines for biliary tract cancer have been updated with the times, but there are still some differences with the consensus of domestic experts on the management of biliary tract cancer. While referring to the NCCN guidelines, we should carry out clinical work in accordance with the actual situation in China.