Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations

Marcano-Bonilla, Lorena; Mohamed, Essa A.; Mounajjed, Taofic; Roberts, Lewis R.

doi:10.21037/cco.2016.10.09

Cited by 105 publications

(86 citation statements)

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“…Intrahepatic cholangiocarcinoma is a very heterogenous tumor, with multiple morphologies on gross, cellular, and molecular levels. Risk factors for ICC activate the inflammatory response, leading to increased cholangiocyte proliferation and the production of free radicals and multiple other cytokines and chemicals which continue the cycle of injury and growth, creating an ideal environment for carcinogenesis …”

Section: Discussionmentioning

confidence: 99%

Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease

et al. 2019

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Background To investigate the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status. Methods In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan‐Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA). Results About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child‐Pugh A patients (P < 0.01). In Child‐Pugh B/C patients, this survival difference became nonsignificant (P = 0.22). Increased NLR and SII were associated with decreased survival (P < 0.01), while dichotomized PLR was not (P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child‐Pugh class A (n = 94), low‐NLR had higher OS vs high‐NLR (25.4 vs 12.2 months, P < 0.01). In Child‐Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low‐ vs high‐NLR: 6.7 vs 2.9 months, P = 0.2). Child‐Pugh class acted as an effect modifier on MVA for NLR (P = 0.0124). Conclusions The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease.

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Section: Discussionmentioning

confidence: 99%

Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease

et al. 2019

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“…Biliary tract cancer is the sixth leading cause of cancer‐related deaths in Japan . The prognosis of BTC is poor because most patients present at advanced stages and are thus diagnosed with unresectable tumors . The standard first‐line treatment for locally advanced or metastatic BTC is systemic chemotherapy with cisplatin and gemcitabine .…”

Section: Introductionmentioning

confidence: 99%

“…2 The prognosis of BTC is poor because most patients present at advanced stages and are thus diagnosed with unresectable tumors. 3,4 The standard first-line treatment for locally advanced or metastatic BTC is systemic chemotherapy with cisplatin and gemcitabine. 3,5,6 The alternative regimen with tegafur (S-1), an oral fluoropyrimidine, has shown a comparable response rate (RR) as that with gemcitabine.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of trametinib in Japanese patients with advanced biliary tract cancers refractory to gemcitabine

et al. 2017

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Gemcitabine‐based therapy remains the mainstay of treatment for patients with biliary tract cancers (BTCs) with no second‐line treatment(s) established yet. Aberrant activation of the MAPK pathway in patients with BTC indicates its importance in BTC. Trametinib is a potent, highly selective, allosteric non‐competitive inhibitor of MEK1/MEK2. In this phase IIa open‐label, single‐arm study, we investigated the efficacy and safety of trametinib in Japanese patients with advanced BTC refractory to gemcitabine‐based therapy. All patients received oral trametinib 2 mg once daily until progressive disease (PD), death, or unacceptable toxicity. The primary objective was to determine the 12‐week non‐PD rate. Secondary assessments included safety, progression‐free survival (PFS), overall survival, and overall response rate. Targeted exome sequencing was used to identify biomarkers for sensitivity or resistance to trametinib monotherapy. Twenty patients (median age, 61.5 years) with carcinoma of gall bladder (40%), intrahepatic (25%) or extrahepatic (30%) bile duct, and ampulla of Vater (5%) were enrolled. The non‐PD rate at week 12 was 10% (95% confidence interval, 1.2‐31.7); it did not reach the threshold rate of 25%. Median PFS was 10.6 weeks (95% confidence interval, 4.6‐12.1) and 1‐year overall survival was 20.0%. Stable disease and PD were observed in 13 (65%) and seven (35%) patients, respectively. No new safety signals were reported. Although the primary end‐point was not met, prolonged PFS was observed in one patient having six somatic variants including synonymous NF1 exon 12 splice variant and a loss‐of‐function variant in ARID1A. Efforts to understand responsive mutations and sensitivity to targeted therapies are warranted. This trial was registered with ClinicalTrials.gov: NCT01943864.

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“…14 Chronic inflammation, Caroli's disease, choledochal cysts, infectious diseases as well as a variety of biological and chemical toxins are further factors associated with biliary cancer development. 14 The carcinogenesis of biliary neoplasm is thought to be a multi-step process from metaplasia to malignant degeneration. Antral metaplasia, hyperplasia, non-neoplastic polyps represent non-neoplastic lesions and can be found in around 9-59.5% of cases after cholecystectomy.…”

Section: Discussionmentioning

confidence: 99%

Cystic duct dysplasia after cholecystectomy: a systematic review of the literature

Mongelli¹,

Cianfarani²,

Giuseppe³

et al. 2019

Int Surg J

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In this article, we discuss the matter and suggest a possible management algorithm. METHODS Search strategyTwo researchers independently searched the PubMed, Cochrane Library and Google Scholar databases by combining "cholecystectomy" and "dysplasia" and ABSTRACT Approximately 1 to 3.5% of cholecystectomies are found to have incidental dysplasia on histological examination. Cases of positive resection margins on the cystic stump are rare and evidence lack. The aim of this article was to systematically review the literature and to suggest a possible management algorithm. We searched PubMed, Cochrane Library and Google Scholar databases by combining "cholecystectomy" and "dysplasia" and "cystic" according to preferred reporting items for systematic reviews and meta-analyses guidelines. Studies providing information about cystic duct dysplasia with positive resection margin after cholecystectomy were included. We identified 113 articles, of which three were considered eligible. Five patients had a high-grade dysplasia, one patient had a carcinoma and one had a low-grade dysplasia. Median follow-up was of 10.5 months (range: 0.5-26.6 months), no evidence of recurrence was found in patients with dysplasia, while the patient with diagnosis of cholangiocarcinoma died during follow-up. Patients with positive resection margins for dysplasia after cholecystectomy should be considered for a surgical treatment according to clinical and pathological factors. Simple cystic duct stump excision was suggested and seems to be safe and effective with no evidence of recurrence during follow-up when a R0 resection is achieved. A multidisciplinary approach and a surveillance program should be always taken into account.

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Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations

Cited by 105 publications

References 0 publications

Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease

Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease

Efficacy and safety of trametinib in Japanese patients with advanced biliary tract cancers refractory to gemcitabine

Cystic duct dysplasia after cholecystectomy: a systematic review of the literature

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