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Gallbladder and Biliary Tract Diseases

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 26114

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Dr. Christian Mayr

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1. Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria
2. Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria
Interests: biliary tract cancer; epigenetics; cancer stem cells; chemoresistance; ferroptosis

Special Issue Information

Dear Colleagues,

The biliary tract system is responsible for the modification, transport, and concentration/storage of bile. Diseases of the gallbladder and the biliary tract system are often painful and severe. Chronic inflammation of the gallbladder and the biliary tract system can lead to the development of biliary tract cancer (BTC).

Epidemiological data show strong geographic variations regarding the incidence of BTC—in Europe and the United States, BTC is a relatively rare (but still the second most common primary liver tumor) disease (four per 100,000 population per year), whereas in some regions of Southeast Asia, BTC is very frequent. This observation is explainable by the consumption of undercooked food in these regions, leading to liver fluke infestation and inflammation.

Although BTC is relatively rare in the Western world, incidences are rising, probably as a result of a generally unhealthy lifestyle, as, besides primary sclerosing cholangitis, cholangitis, or HBV and HCV infection, obesity, tobacco consumption, and alcohol consumption represent risk factors for the development of BTC.

The prognosis for patients with BTC remains dismal, despite the remarkable advances in cancer research. Because of the silent and unspecific symptoms, patients are often diagnosed with BTC at an already advanced stage, eliminating the possibility for surgery. The standard therapy for patients with advanced BTC is a combination of cisplatin and gemcitabine, resulting in a median survival of only about one year.

Therefore, research regarding gallbladder and biliary tract diseases is of the utmost importance in order to better understand the various diseases, as well as to develop new therapeutic strategies.

Dr. Christian Mayr
Guest Editor

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Keywords

Gallbladder diseases
Biliary tract diseases
Cholangiocarcinoma
Biliary tract cancer
Bile duct cancer
Gallbladder cancer
Primary sclerosing cholangitis
Cholangitis
Cholecystitis
Gall stones

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Published Papers (7 papers)

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Research

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26 pages, 1672 KiB

Open AccessArticle

Prognostic Relevance of the Eighth Edition of TNM Classification for Resected Perihilar Cholangiocarcinoma

by Hans-Michael Hau, Felix Meyer, Nora Jahn, Sebastian Rademacher, Robert Sucher and Daniel Seehofer

J. Clin. Med. 2020, 9(10), 3152; https://doi.org/10.3390/jcm9103152 - 29 Sep 2020

Cited by 10 | Viewed by 2702

Abstract

Objectives: In our study, we evaluated and compared the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system in patients undergoing surgery for perihilar cholangiocarcinoma (PHC). Methods: Patients undergoing liver surgery with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. Results: Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1–33.9), and the three- and five-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition vs. the 7th edition resulted in the reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th editions were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system showed a trend to better discrimination, with an AUC of 0.69 (95% CI: 0.52–0.84) compared to 0.61 (95% CI: 0.51–0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age >65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, and lymph node involvement, such as no caudate lobe resection, as independent predictors of poor survival (p < 0.05). Conclusions: In the current study, the newly released 8th edition of AJCC staging system showed no significant benefit compared to the previous 7th edition in predicting the prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma. Further research may help to improve the prognostic value of the AJCC staging system for PHC—for instance, by identifying new prognostic markers or staging criteria, which may improve that individual patient’s outcome. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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10 pages, 656 KiB

Open AccessArticle

Changed Profile of Serum Transferrin Isoforms in Primary Biliary Cholangitis

by Agnieszka Grytczuk, Alicja Bauer, Ewa Gruszewska, Bogdan Cylwik and Lech Chrostek

J. Clin. Med. 2020, 9(9), 2894; https://doi.org/10.3390/jcm9092894 - 8 Sep 2020

Cited by 5 | Viewed by 2151

Abstract

Liver damage affects the synthesis of proteins and glycoproteins, and alters their posttranslational modification, such as glycosylation changing the serum profile of glycoprotein isoforms. The retention of hydrophobic bile acids in the course of cholestatic liver diseases is a major cause of liver damage in primary biliary cholangitis (PBC). The study objective was to determine the serum profile of transferrin isoforms in primary biliary cholangitis and compare it to transferrin isoforms profile in extrahepatic cholestasis. The study was carried out in 76 patients with PBC and 40 healthy blood donors. Transferrin isoforms were analyzed by the capillary electrophoresis method. The mean relative concentrations of disialotransferrin and trisialotransferrin in PBC were significantly lower than those in the healthy subjects (p < 0.001, p = 0.011; respectively). None of the transferrin isoforms changed according to the disease severity evaluated by the Ludwig scoring system. However, the disease stage affected the activity of alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT), and albumin level (p = 0.002; p = 0.013 and p = 0.005, respectively). Our results indicate that serum profile of transferrin isoforms alters primary biliary cholangitis and differs in comparison to transferrin isoforms profile in extrahepatic cholestasis. The decreased concentrations of lower sialylated isoforms of transferrin (low percentage share in total transferrin level) are not associated with the histological stage of disease. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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11 pages, 1049 KiB

Open AccessFeature PaperArticle

Incidental Carcinoma after Cholecystectomy for Benign Disease of the Gallbladder: A Meta-Analysis

by Jung-Soo Pyo, Byoung Kwan Son, Hyo Young Lee, Il Whan Oh and Kwang Hyun Chung

J. Clin. Med. 2020, 9(5), 1484; https://doi.org/10.3390/jcm9051484 - 14 May 2020

Cited by 18 | Viewed by 3287

Abstract

This study aimed to determine the incidence and the prognosis of incidental carcinoma of the gallbladder (IGBC) after cholecystectomy through a meta-analysis. This meta-analysis included 51 studies and 436,636 patients with cholecystectomy. The incidence rate of IGBC after cholecystectomy was 0.6% (95% confidence interval (CI) 0.5–0.8%). The incidence rate of recent studies was not significantly different from those of past studies. The mean age and female ratio of the IGBC subgroup were not significantly different from those of the overall patient group. The estimated rates of IGBC were 13.0%, 34.1%, 39.7%, 22.7%, and 12.5% in the pTis, pT1, pT2, pT3, and pT4 stages, respectively. Patients with IGBC had a favorable overall survival rate compared to patients with non-IGBC (hazard ratio (HR) 0.574, 95% CI 0.445–0.739). However, there was no significant difference of disease-free survival between the IGBC and non-IGBC subgroups (HR 0.931, 95% CI 0.618–1.402). IGBC was found in 0.6% of patients with cholecystectomy. The prognosis of patients with IGBC was favorable compared to those with non-IGBC. In the pathologic examination after cholecystectomy for benign diseases, a sufficient examination for histology should be guaranteed to detect IGBC. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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13 pages, 723 KiB

Open AccessArticle

Leakage and Stenosis of the Hepaticojejunostomy Following Surgery for Perihilar Cholangiocarcinoma

by Jan Bednarsch, Zoltan Czigany, Daniel Heise, Sven Arke Lang, Steven W. M. Olde Damink, Tom Luedde, Philipp Bruners, Tom Florian Ulmer and Ulf Peter Neumann

J. Clin. Med. 2020, 9(5), 1392; https://doi.org/10.3390/jcm9051392 - 8 May 2020

Cited by 12 | Viewed by 3378

Abstract

This study aims to provide a deep insight into the incidence and clinical significance of postoperative anastomotic leakage (AL) and anastomotic stenosis (AS) of the hepaticojejunostomy (HJ) after curative-intent liver resection for perihilar cholangiocarcinoma (pCCA). Between 2011 and mid-2019, 114 patients with pCCA underwent surgery in curative intent at our institution and were analyzed regarding the postoperative incidence of AL and AS. Further, associations between AL and AS and clinical characteristics were assessed using multiple univariate logistic regression analyses. AL was diagnosed in 11.4% (13/114) of the patients resulting in postoperative mortality in the minority of patients (23.0%, 3/13). AS occurred in 11.0% (11/100) of the individuals eligible for follow-up with local tumor recurrence being the underlying pathology in 72.7% (8/11) of the cases. None of the investigated clinical factors including surgical difficulty of the HJ showed a meaningful association with AL or AS. AL and AS are frequent complications and can be treated by conservative, interventional or surgical therapy with a high success rate. Also, technical difficulty of the HJ appears not to be not associated with the occurrence of AL or AS. Moreover, AS is associated with tumor recurrence in the majority of cases. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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14 pages, 8141 KiB

Open AccessArticle

Gallbladder Radiation Protection in SIRT—Quantitative Anatomical Study of Hepatic Vasculature

by Piotr Piasecki, Krzysztof Brzozowski, Piotr Ziecina, Marek Wierzbicki, Anna Budzynska, Andrzej Mazurek, Miroslaw Dziuk, Maciej Maciak, Edward Iller and Jerzy Narloch

J. Clin. Med. 2019, 8(10), 1531; https://doi.org/10.3390/jcm8101531 - 24 Sep 2019

Cited by 2 | Viewed by 2830

Abstract

Introduction: This study was designed to assess quantitatively a safe position of the microcatheter during the SIRT (Selective Internal Radiation Therapy) procedure, in order to minimize the risk of non-target spheres leaking. Materials and Methods: Retrospective analysis of the distance of the tip of the microcatheter from coiled or patent non-target arteries was measured during ^99mTc-MAA work-up procedure. Frequency of extrahepatic leaking during work-up and SIRT procedures was evaluated. Results: There were 85 patients who underwent 98 work-up procedures. There were 64 radioembolizations. There were 44 gastroduodenal, 51 right gastric, and 54 cystic artery embolizations performed. Extrahepatic ^99mTc-MAA leaking was observed in 33 cases: 16 to gallbladder, four to a gastric wall, nine to the duodenum, one to the intestinal wall, and three to the abdominal wall. Leak in ^99mTc-MAA was also related to the presence of additional arteries (p = 0.009). There were 34 proximal and 31 distal to cystic artery ^99mTc-MAA injections resulting in 12 vs. four leaks, respectively (p = 0.039, RR-2.5). Mean distance of the tip of the microcatheter from the origin of the cystic artery was 20 mm (minimum of 2.1 mm and maximum of 53 mm) proximally and 10 mm (minimum 1 mm and maximum 51 mm) distally (ns). Conclusions: Leaking in ^99mTc-MAA (^99mTc - labelled macroaggregated albumin) was related to the presence of additional arteries. Regardless of cystic artery embolization, it is 2.5 times safer to inject microspheres distal to its origin, compared to proximal injection. Cystic artery origin relative to the right hepatic artery division usually necessitates embolization of the former. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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Review

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31 pages, 2365 KiB

Open AccessReview

Long Non-Coding RNAs in Biliary Tract Cancer—An Up-to-Date Review

by Dino Bekric, Daniel Neureiter, Markus Ritter, Martin Jakab, Martin Gaisberger, Martin Pichler, Tobias Kiesslich and Christian Mayr

J. Clin. Med. 2020, 9(4), 1200; https://doi.org/10.3390/jcm9041200 - 22 Apr 2020

Cited by 10 | Viewed by 4643

Abstract

The term long non-coding RNA (lncRNA) describes non protein-coding transcripts with a length greater than 200 base pairs. The ongoing discovery, characterization and functional categorization of lncRNAs has led to a better understanding of the involvement of lncRNAs in diverse biological and pathological processes including cancer. Aberrant expression of specific lncRNA species was demonstrated in various cancer types and associated with unfavorable clinical characteristics. Recent studies suggest that lncRNAs are also involved in the development and progression of biliary tract cancer, a rare disease with high mortality and limited therapeutic options. In this review, we summarize current findings regarding the manifold roles of lncRNAs in biliary tract cancer and give an overview of the clinical and molecular consequences of aberrant lncRNA expression as well as of underlying regulatory functions of selected lncRNA species in the context of biliary tract cancer. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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15 pages, 3436 KiB

Open AccessReview

An Overview on Primary Sclerosing Cholangitis

by Cătălina Vlăduţ, Mihai Ciocîrlan, Dana Bilous, Vasile Șandru, Mădălina Stan-Ilie, Nikola Panic, Gabriel Becheanu, Mariana Jinga, Raluca S. Costache, Daniel O. Costache and Mircea Diculescu

J. Clin. Med. 2020, 9(3), 754; https://doi.org/10.3390/jcm9030754 - 11 Mar 2020

Cited by 15 | Viewed by 5998

Abstract

Primary sclerosing cholangitis is a progressive liver disease characterized by chronic inflammation leading to liver fibrosis and cirrhosis. Even though the exact pathogenesis is still unclear, a combination of autoimmune, environmental, and ischemic factors could explain certain aspects of the disease. The most important diagnostic step is cholangiography, which can be obtained either by endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiography (MRCP as the gold standard), or percutaneous transhepatic cholangiography. It shows multifocal short biliary duct strictures leading to the “beaded” aspect. Cholangiocarcinoma and colorectal adenocarcinoma are the most feared complications in patients with Primary sclerosing cholangitis (PSC). Continuous screening consists of annual clinical, biochemical, and ultrasound assessments in asymptomatic patients and annual colonoscopy in patients with PSC and inflammatory bowel disease. In newly diagnosed patients with PSC, colonoscopy is mandatory and, if negative, then, a repeat colonoscopy should be performed in 3–5 years. The lack of efficient curative medical treatment makes invasive treatments such as liver transplant and endoscopy the mainstream for managing PSC and its complications. Until now, even though only ursodeoxycholic acid has shown a moderate clinical, biochemical, and even histological improvement, it has no significant influence on the risk of cholangiocarcinoma, liver transplant need, or death risk and it is no longer recommended in treating early PSC. Further studies are in progress to establish the effect of molecular-targeted therapies in PSC. Full article

(This article belongs to the Special Issue Gallbladder and Biliary Tract Diseases)

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