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Cancers
Special Issues
Pathophysiology and Treatment of Gallbladder Cancer
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Pathophysiology and Treatment of Gallbladder Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 24655

Special Issue Editors

Dr. Philip De Reuver

E-Mail Website
Guest Editor
Department of Surgery, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands
Interests: biliary disease; rare cancers; shared decision making; health care efficiency
Dr. Chella van der Post

E-Mail Website
Guest Editor
Department of Pathology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands
Interests: detection; clinical

Special Issue Information

Dear Colleagues,

Gallbladder cancer (GBC) is a rare and highly lethal neoplasm of the biliary tract. GBC demonstrates significant geographic, age-, gender-, and ethnicity-related differences in incidence, but the cause of GBC and it’s pathophysiology is not well understood. (Epi)Genetics or environmental factors may play an essential role in the development of GBC. Other possible risk factors include cholelithiasis, obesity, gallbladder polyps, chronic infections, and an abnormal pancreaticobiliary duct junction. However, most patients with GBC do not have any of the known risk factors apart from age. It could be hypothesized that different causes of gallbladder cancer also imply different treatment strategies.

This Special Issue will focus on the current insights into the pathophysiology, treatment and predictive factors for survival of gallbladder cancer in different geographic area’s.  This issue aims to improve our understanding in the development of GBC. We look forward to your contributions.

Dr. Philip De Reuver
Dr. Chella van der Post
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gallbladder cancer
  • pathophysiology
  • risk factors

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 166 KiB  
Editorial
Clinicopathological and Molecular Insights into Gallbladder Cancer
by Philip R. de Reuver and Rachel S. van der Post
Cancers 2023, 15(10), 2728; https://doi.org/10.3390/cancers15102728 - 12 May 2023
Cited by 2 | Viewed by 1294
Abstract
Although gallbladder cancer (GBC) is rare, it is one of the few cancers with a higher mortality rate than incidence, accounting for 1 [...] Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)

Research

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7 pages, 1338 KiB  
Article
Quality Assessment of Gallbladder Cancer Pathology Reports: A Dutch Nationwide Study
by Tessa J. J. de Bitter, Elise A. J. de Savornin-Lohman, Philip R. de Reuver, Valerie Sophie Versteeg, Elisa Vink-Börger, Joanne Verheij, Iris D. Nagtegaal and Rachel S. van der Post
Cancers 2021, 13(12), 2977; https://doi.org/10.3390/cancers13122977 - 14 Jun 2021
Cited by 6 | Viewed by 2237
Abstract
Adequate reporting of pathological findings is essential for optimal patient management and to perform high-quality research. The aim of this study was to assess the completeness of pathology reports of gallbladder cancer (GBC) at the nationwide level to assess guideline adherence and make [...] Read more.
Adequate reporting of pathological findings is essential for optimal patient management and to perform high-quality research. The aim of this study was to assess the completeness of pathology reports of gallbladder cancer (GBC) at the nationwide level to assess guideline adherence and make recommendations for improvement. A retrospective population-based cohort of GBC patients diagnosed in the Netherlands from 2000 to 2019 was collected using data from the Dutch Cancer Registry and the nationwide network and registry of histology. Pathology reports were scored on the presence and content of essential and optional items according to the Dutch consensus-based guideline on biliary tract cancer. By histopathological review of cases, we compared findings with the conclusion of the corresponding pathology report. All pathology reports (n = 849) had a narrative, nonstructured format. Overall completeness was low. Information on key prognostic factors, such as tumor side (hepatic vs. serosal), status of cystic duct and liver surgical margins and venous and perineural invasion, was frequently lacking (80%, 23%, 59%, 74% and 74% missing, respectively). Whereas certain items were often missing from the report, they could be retrospectively detected in a substantial proportion of cases during pathology review (n = 738). In conclusion, significant improvements could be made in the reporting of GBC in the Netherlands. Synoptic reporting could greatly enhance the completeness of reports, as already demonstrated for tumor types. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)
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Review

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25 pages, 687 KiB  
Review
Gallbladder Cancer: Current Multimodality Treatment Concepts and Future Directions
by Niklas Sturm, Jasmin Selina Schuhbaur, Felix Hüttner, Lukas Perkhofer and Thomas Jens Ettrich
Cancers 2022, 14(22), 5580; https://doi.org/10.3390/cancers14225580 - 14 Nov 2022
Cited by 24 | Viewed by 3755
Abstract
Gallbladder cancer (GBC) is the most common primary tumor site of biliary tract cancer (BTC), accounting for 0.6% of newly diagnosed cancers and 0.9% of cancer-related deaths. Risk factors, including female sex, age, ethnic background, and chronic inflammation of the gallbladder, have been [...] Read more.
Gallbladder cancer (GBC) is the most common primary tumor site of biliary tract cancer (BTC), accounting for 0.6% of newly diagnosed cancers and 0.9% of cancer-related deaths. Risk factors, including female sex, age, ethnic background, and chronic inflammation of the gallbladder, have been identified. Surgery is the only curative option for early-stage GBC, but only 10% of patients are primary eligible for curative treatment. After neoadjuvant treatment, up to one-third of locally advanced GBC patients could benefit from secondary surgical treatment. After surgery, only a high-risk subset of patients benefits from adjuvant treatment. For advanced-stage GBC, palliative chemotherapy with gemcitabine and cisplatin is the current standard of care in line with other BTCs. After the failure of gemcitabine and cisplatin, data for second-line treatment in non-resectable GBC is poor, and the only recommended chemotherapy regimen is FOLFOX (5-FU/folinic acid and oxaliplatin). Recent advances with the PD-L1 inhibitor durvalumab open the therapy landscape for immune checkpoint inhibition in GBC. Meanwhile, targeted therapy approaches are a cornerstone of GBC therapy based on molecular profiling and new evidence of molecular differences between different BTC forms and might further improve the prognosis of GBC patients. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)
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14 pages, 2170 KiB  
Review
Palliation in Gallbladder Cancer: The Role of Gastrointestinal Endoscopy
by Tommaso Schepis, Ivo Boškoski, Andrea Tringali, Vincenzo Bove and Guido Costamagna
Cancers 2022, 14(7), 1686; https://doi.org/10.3390/cancers14071686 - 26 Mar 2022
Cited by 9 | Viewed by 3136
Abstract
Gallbladder cancer is a rare malignancy burdened by poor prognosis with an estimated 5-year survival of 5% to 13% due to late presentation, early infiltration of surrounding tissues, and lack of successful treatments. The only curative approach is surgery; however, more than 50% [...] Read more.
Gallbladder cancer is a rare malignancy burdened by poor prognosis with an estimated 5-year survival of 5% to 13% due to late presentation, early infiltration of surrounding tissues, and lack of successful treatments. The only curative approach is surgery; however, more than 50% of cases are unresectable at the time of diagnosis. Endoscopy represents, together with surgery and chemotherapy, an available palliative option in advanced gallbladder cancers not eligible for curative treatments. Cholangitis, jaundice, gastric outlet obstruction, and pain are common complications of advanced gallbladder cancer that may need endoscopic management in order to improve the overall survival and the patients’ quality of life. Endoscopic biliary drainage is frequently performed to manage cholangitis and jaundice. ERCP is generally the preferred technique allowing the placement of a plastic stent or a self-expandable metal stent depending on the singular clinical case. EUS-guided biliary drainage is an available alternative for patients not amenable to ERCP drainage (e.g., altered anatomy). Gastric outlet obstruction is another rare complication of gallbladder malignancy growing in contact with the duodenal wall and causing its compression. Endoscopy is a less invasive alternative to surgery, offering different options such as an intraluminal self-expandable metal stent or EUS-guided gastroenteroanastomosis. Abdominal pain associated with cancer progression is generally managed with medical treatments; however, for incoercible pain, EUS-guided celiac plexus neurolysis has been described as an effective and safe treatment. Locoregional treatments, such as radiofrequency ablation (RFA), photodynamic therapy (PDT), and intraluminal brachytherapy (IBT), have been described in the control of disease progression; however, their role in daily clinical practice has not been established yet. The aim of this study is to perform a review of the literature in order to assess the role of endoscopy and the available techniques in the palliative therapy of advanced gallbladder malignancy. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)
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16 pages, 1447 KiB  
Review
Treatment of Resectable Gallbladder Cancer
by Eduardo A. Vega, Sebastian Mellado, Omid Salehi, Richard Freeman and Claudius Conrad
Cancers 2022, 14(6), 1413; https://doi.org/10.3390/cancers14061413 - 10 Mar 2022
Cited by 13 | Viewed by 4174
Abstract
Gallbladder cancer (GBC) is the most common biliary tract cancer worldwide and its incidence has significant geographic variation. A unique combination of predisposing factors includes genetic predisposition, geographic distribution, female gender, chronic inflammation, and congenital developmental abnormalities. Today, incidental GBC is the most [...] Read more.
Gallbladder cancer (GBC) is the most common biliary tract cancer worldwide and its incidence has significant geographic variation. A unique combination of predisposing factors includes genetic predisposition, geographic distribution, female gender, chronic inflammation, and congenital developmental abnormalities. Today, incidental GBC is the most common presentation of resectable gallbladder cancer, and surgery (minimally invasive or open) remains the only curative treatment available. Encouragingly, there is an important emerging role for systemic treatment for patients who have R1 resection or present with stage III–IV. In this article, we describe the pathogenesis, surgical and systemic treatment, and prognosis. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)
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16 pages, 558 KiB  
Review
Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022
by Zishuo Ian Hu and Kian-Huat Lim
Cancers 2022, 14(5), 1249; https://doi.org/10.3390/cancers14051249 - 28 Feb 2022
Cited by 11 | Viewed by 4301
Abstract
Gallbladder cancer (GBC) is a biological, anatomical, and clinically distinct subset of biliary tract cancers (BTC), which also include extra- and intra-hepatic cholangiocarcinoma. The advent of next-generation sequencing (NGS) clearly shows that GBC is genetically different from cholangiocarcinoma. Although GBC is a relatively [...] Read more.
Gallbladder cancer (GBC) is a biological, anatomical, and clinically distinct subset of biliary tract cancers (BTC), which also include extra- and intra-hepatic cholangiocarcinoma. The advent of next-generation sequencing (NGS) clearly shows that GBC is genetically different from cholangiocarcinoma. Although GBC is a relatively rare cancer, it is highly aggressive and carries a grave prognosis. To date, complete surgical resection remains the only path for cure but is limited to patients with early-stage disease. The majority of the patients are diagnosed at an advanced, inoperable stage when systemic treatment is administered as an attempt to enable surgery or for palliation. Gemcitabine and platinum-based chemotherapies have been the main treatment modality for unresectable, locally advanced, and metastatic gallbladder cancer. However, over the past decade, the treatment paradigm has evolved. These include the introduction of newer chemotherapeutic strategies after progression on frontline chemotherapy, incorporation of targeted therapeutics towards driver mutations of genes including HER2, FGFR, BRAF, as well as approaches to unleash host anti-tumor immunity using immune checkpoint inhibitors. Notably, due to the rarity of BTC in general, most clinical trials included both GBC and cholangiocarcinomas. Here, we provide a review on the pathogenesis of GBC, past and current systemic treatment options focusing specifically on GBC, clinical trials tailored towards its genetic mutations, and emerging treatment strategies based on promising recent clinical studies. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)
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Other

20 pages, 1334 KiB  
Systematic Review
Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
by Hendrien Kuipers, Tessa J. J. de Bitter, Marieke T. de Boer, Rachel S. van der Post, Maarten W. Nijkamp, Philip R. de Reuver, Rudolf S. N. Fehrmann and Frederik J. H. Hoogwater
Cancers 2021, 13(21), 5257; https://doi.org/10.3390/cancers13215257 - 20 Oct 2021
Cited by 27 | Viewed by 4500
Abstract
Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search [...] Read more.
Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search was performed utilizing PubMed, EMBASE, Cochrane Library, and Web of Science. Only studies reporting genetic alterations in human GBC were included. In total, data were extracted from 62 articles, describing a total of 3893 GBC samples. Frequently detected genetic alterations (>5% in >5 samples across all studies) in GBC for which targeted therapies are available in other cancer types included mutations in ATM, ERBB2, and PIK3CA, and ERBB2 amplifications. High tumor mutational burden (TMB-H) and microsatellite instability (MSI-H) were infrequently observed in GBC (1.7% and 3.5%, respectively). For solid cancers with TMB-H or MSI-H pembrolizumab is FDA-approved and shows an objective response rates of 50% for TMB-H GBC and 41% for MSI-H biliary tract cancer. Only nine clinical trials evaluated targeted therapies in GBC directed at frequently altered genes (ERBB2, ARID1A, ATM, and KRAS). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Gallbladder Cancer)
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