Management Of Biliary Tract Cancer Research Articles

Clinical practice guidelines for the management of biliary tract cancers: major revised points for the third edition

Clinical practice guidelines for the management of biliary tract cancers: major revised points for the third edition

Prognostic Factors and Impact of Immunohistochemistry in the Management of Biliary Tract Cancer– A Single Center Experience in Germany

Prognostic Factors and Impact of Immunohistochemistry in the Management of Biliary Tract Cancer– A Single Center Experience in Germany

Biliary tract cancer stem cells - translational options and challenges.

Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells - the cancer stem cells - possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.

Surgical management of biliary tract cancers.

Biliary tract cancers (BTC) are aggressive gastrointestinal malignancies that are associated with a poor prognosis. This rare group of tumors includes cancers of the gallbladder, intrahepatic, and extrahepatic biliary tree. Chronic inflammatory processes such as cholelithiasis and chronic bacterial infection of the biliary system remain the most common underlying risk factor although most cases occur sporadically. The majority of patients present with advanced disease accompanied by nonspecific symptoms, making BTCs a therapeutic challenge for clinicians. In patients with localized, resectable disease, the only potentially curative treatment is a complete resection with negative microscopic margins. Liver transplantation has been used in selected patients with peri-hilar cholangiocarcinoma, with acceptable results. Recurrence rates remain high despite surgical treatment and 5-year survival rates range from 8-40% in patients treated with resection. In this review, we will summarize the current surgical management strategies for BTCs, focusing on the role of resection.

Lynch 症候群における胆道癌の特徴と サーベイランス戦略上の位置づけ

Lynch 症候群における胆道癌の特徴と サーベイランス戦略上の位置づけ

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers.

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC.

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidence-based approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via http://www.jshbps.jp/en/guideline/biliary-tract2.html.

A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study

The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. NCT00753675.

The identification of the age effects in 1,287 patients with biliary tract cancer.

244 Background: Age is a mirror for pathogenesis in some of biliary tract cancer (BTC) as liver fluke- or pancreaticobiliary maljunction-associated BTCs. However, the age effects including prognosis in BTC were not fully understood. The identification of the age effects might be helpful for the management of BTC. Methods: For the years 1992-2014, 1287 patients receiving initial treatment for BTC in our institution were reviewed. According to age at diagnosis of BTC, patients were divided into the five age groups as <50, 50-59, 60-69, 70-79, and ≥80. The relationships between overall survival time (OS) and the five age groups were analyzed using wilcoxon test to choose a prognostic cut-off of age. On the basis of a prognostic cut-off of age, the prognostic age classification was constructed. The multivariate analysis with logistic regression modeling was performed to determine the influence of gender, Eastern Cooperative Oncology Group performance status scale [ECOG-PS], primary site, and metastatic site on the prognostic age classification. Results: Median age was 67 years with male 59%. ECOG PS of 0 was 63.7%.The sites of primary tumor included intrahepatic (25.2%) and extrahepatic bile duct (34.0%), gallbladder (31.9%) and ampulla of Vater (8.9%). The prognostic cut-off of age was age less than 60 (21.8% of all). Median OS in younger patients (age<60, median OS: 7.9mo) was shorter than that in elder patients (age≥60, median OS 12.4mo, P<0.01). In univariate analysis, the prevalence of bone metastasis, distal lymph node metastasis and peritoneal dissemination was higher in younger BTC than elder patients. Multivariate analysis revealed that peritoneal dissemination was an independent younger BTC related-factor (OR=1.9, P<0.01). Conclusions: Younger BTC patients (age<60) showed poor prognosis and the high frequency of peritoneal dissemination, compared to elder BTC patients. The relationship between age and peritoneal dissemination of BTC might be a key to elucidate the age effect concomitant with poor prognosis.

Targeted agents: how can we improve the outcome in biliary tract cancer?

The management of biliary tract cancer (BTC) has deeply changed in the past decade. Just few years ago patients with advanced disease had no effective treatment options but supportive therapy. Palliative chemotherapy was often administered in the absence of evidence of efficacy, as no randomized studies were available.

Advanced Biliary Tract Cancers

Single-agent management of metastatic biliary tract cancers with 5-fluorouracil (5-FU) or gemcitabine has shown limited efficacy, although 5-FU has been shown to be more effective than best supportive care alone. An analysis of phase II trials has suggested that platinums enhanced the efficacy of single-agent fluoropyrimidines. In a phase III randomized trial comparing single-agent gemcitabine with gemcitabine plus cisplatin, the gemcitabine/cisplatin combination significantly improved median overall survival (OS) and progression-free survival (PFS), which established a new option for standard of care. However, the future of cancer medicine lies in newer, targeted agents. In the management of biliary tract cancers, preliminary evidence with epidermal growth factor receptor inhibitors has already demonstrated activity. This article reviews systemic therapies for metastatic biliary tract cancers as they relate to current and emerging standards of care.

Nonsurgical therapy of biliary tract cancer

The management of biliary tract cancers (BTCs) has been challenging partly because of the lack of robust data to define a treatment standard. This in turn has been because of the difficulty in conducting large clinical studies in an uncommon cancer, as well as managing elderly and unwell patients. Recent data and improvements in multidisciplinary patient management have established a standard of care and delivered insights into the natural history of this uncommon cancer. This is critical at a time when the incidence of this malignancy is increasing. This article describes the improving multidisciplinary management as well as seminal randomized data describing standard management. Current clinical trials that are likely to further impact on future management are described. These large datasets provide insights into the natural history of BTCs hitherto not forthcoming from the many smaller studies which formed the historical evidence base. This increasing standardization of care will improve outcome for patients with BTCs and provide a platform for further research.

Trends in the incidence and management of biliary tract cancer: A French population-based study

The trends in incidence and management of biliary tract cancer (BTC) were investigated in a well-defined French population over a 30-year period (1976-2005). Data were obtained from the Burgundy digestive cancer registry. Age-standardised incidence rates and trends in incidence were determined. Treatment and stage at diagnosis were also investigated. Five-year survival rates were calculated. Six hundred and fifteen cases of BTC were recorded. There was no significant change in BTC incidence over the 30-year period. For extrahepatic BTC age-standardised incidence rates were 1.1/100,000 for 1976-80 and 2001-2005. These rates were respectively 0.3 and 0.2/100,000 for intrahepatic BTC. The proportion of patients undergoing resection for cure increased over time from 4.8% to 14.2% (p<0.001). The proportion of stage I-II cases ranged from 3.2% to 7.1% but did not vary significantly over time (p=0.55). Most cases were metastatic or unresectable at diagnosis. Five-year relative survival rates were 4.5% for 1976-85 and 6.7% for 1996-2005, ranging from 35.1% for stages I-II to 4.3% for advanced BTC. Age and stage at diagnosis were independent prognostic factors. The incidence of BTC has remained stable in Burgundy over the past 30 years. BTC prognosis remains poor and has only improved slightly over time.

Evidence-based guidelines for the management of biliary tract cancer

胆道癌は,胆管癌,胆嚢癌,乳頭 部癌からなる.リスク因子として, 胆管癌が胆管拡張型膵胆管合流異 常,原発性硬化性胆管炎,胆嚢癌が 胆管非拡張型膵胆管合流異常などの 疾患が挙げられる.胆管癌の初発 症状は90%が黄疸である.一方,胆 嚢癌は,右上腹部痛.乳頭部癌は,黄 疸,発熱,腹痛が初発症状として多い. 胆道癌を疑った場合,診断のファ ーストステップとして,血液生化学 検査と腹部超音波検査を施行する. 肝胆道系酵素上昇,胆管拡張を認め た場合は,胆道癌の存在が疑われる ためさらに画像で存在診断をすすめ ていく.なお,胆道癌では,CA19-9 が50~79%,CEAが40~70%で上昇 するが,補助診断として考えるべき であり,特に,閉塞性黄疸例では腫 瘍ではなく,黄疸により上昇し,ド レナージ後低下する症例があるので 注意を要する.また,胆管癌,乳頭 部癌では,比較的早期の段階で,黄 疸,血液検査異常を伴う場合も少な くないが,胆嚢癌は進行癌になるま で無症状であることが多い.しかし, 一般的に偶然存在を指摘されない限 り,診断時には進行例が多く,早期 診断は今後の課題と思われる. 診断のセカンドステップとして, 造影CT,MRI,MRCPを施行し, 胆道癌の存在を強く疑う所見を認め た場合,確定診断,病期診断のため 内視鏡的逆行性胆管造影(ERC), 胆汁細胞診,擦過細胞診および超音 波内視鏡検査(EUS)を行う.硬化 性胆管炎などの良性胆道狭窄との鑑 別や進展度診断が困難な場合には経 口的胆道内視鏡(POCS)による精 査も有効である.特に肝門部胆管 癌では進展範囲診断が術式に影響を 与えるため精度の高い診断技術が要 求される. 胆道癌診療ガイドライン 藤 井 雅 邦*,河 本 博 文,山 本 和 秀

Endoscopic management of biliary tract cancer with the Wallstent: Experience in 121 patients

Endoscopic management of biliary tract cancer with the Wallstent: Experience in 121 patients