Gallbladder Cancer: The Recent Progress

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 3693

Special Issue Editors


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Guest Editor
Department of Gastroenterology, Gifu Municipal Hospital, Gifu 500-8513, Japan
Interests: imaging diagnosis and endoscopy of pancreatobiliary diseases; chronic pancreatitis; pancreatic fluid collection following acute pancreatitis
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Guest Editor
Department of Diagnostic Pathology and Research Center of Diagnostic Pathology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513, Japan
Interests: colorectal carcinogenesis; cancer chemiprevention; inflammatory bowel disease; ulcerative colitis; Crohn’s disease; animal model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Gallbladder cancer (GBC) is an aggressive malignancy of the biliary tract and is associated with a poor prognosis (~10% overall 5-year survival). Therefore, early detecting GBC in its initial stage offers patients their best chance of cure, but identification of high-risk patients and appropriate surveillance methods are still controversial.

Worldwide occurrence of GBC is <2/100,000 and rates of incidental diagnosis of laparoscopic cholecystectomy range from 0.28 to 2.10%. GBC predominantly affects elderly patients, mean age being 65 years, and females were more often affected, GBC shows a marked geographical variation in its incidence, with the highest incidences being observed in Chile, India, Pakistan, and Ecuador, while relatively low incidence is noted in many Western countries, except for Latin American and Native American individuals. Low, but still increased risk is seen in Eastern Europe, Israel, and Japan.

Most important risk factor for GBC is chronic cholecystitis, with cholelithiasis: >80% of GBC are associated with gallstone and porcelain gallbladder increases risk. Other risk factors include infections with liver flukes and Salmonella spp., primary sclerosing cholangitis, anatomic anomalies of biliary tree, and gastrointestinal polyposis syndrome.

Multiple histopathologic subtypes of GBC are recognized by the WHO: biliary type is most the common morphology with variants, including mucinous adenocarcinoma, clear cell carcinoma, poorly cohesive carcinoma with or without signet-ring cells, adenosquamous and squamous cell carcinoma, and intestinal-type adenocarcinoma. Common molecular alterations of GBC are mutations (CDKN2A, CDKN2B, ARID1A, PIK3CA, TP53, K-RAS), amplification (ERBB2), microsatellite instability, and promoter methylation of CDKN2A.

GBC can arise from either a pathway involving metaplasia or dysplasia or one in which there is a pre-existing adenoma. In addition, number of genetic alterations have been identified in the pre-invasive and invasive stages of GBC. However, exact carcinogenesis/pathogenesis of GBC remains unknown.

Surgical treatment is the most certain method for the radical cure of GBC, and accurate staging of invasive GBC is essential to determine prognosis and treatment. In addition, chemotherapy, molecular targeted therapy, and radiotherapy are also important for the patients who are difficult to cure with surgery. Moreover, pathological diagnosis using EUS-guided tissue acquisition (EUS-TA) is sometimes needed, and specimens surgically resected or obtained by EUS-TA are also used for genome profiling. Gene therapies are currently spreading, as well as conventional chemotherapy and radiotherapy in the patients with unresectable and recurrence cases, and therefore molecular/genetic diagnosis of entire specimens of GBC is important.

This Special Issue, entitled "Gallbladder Cancer: The Recent Progress", welcomes the latest articles about GBC pathogenesis, gene genetics, diagnosis, surgical treatment, chemotherapy, radiotherapy, and endotherapy, including comprehensive review articles regarding update of GBC. We also welcome the contribution of the challenging works on the subjects listed in the Keywords.

Dr. Keisuke Iwata
Prof. Dr. Takuji Tanaka
Guest Editors

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Keywords

  • gallbladder cancer
  • epidemiology
  • geographic distribution
  • pathogenesis
  • molecular pathology
  • precursor lesion
  • risk factor
  • early detection
  • incidental gallbladder cancer
  • surveillance for high-risk group
  • imaging diagnosis
  • EUS-TA
  • chemotherapy
  • radiotherapy
  • surgical treatment
  • robotic surgery
  • neoadjuvant therapy
  • genome profiling
  • liquid biopsy
  • therapy
  • biomarkers
  • targeting molecular therapy
  • biliary drainage

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Published Papers (2 papers)

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11 pages, 2563 KiB  
Article
Chemo-Free Treatment Using Anti-PD-1 Antibodies with Lenvatinib in Unresectable Gallbladder Cancer: PD-L1 May Be a Potential Biomarker for a Better Outcome
by Tiantian Wu, Changsheng Pu, Xianjia Wu, Qiang Wang and Keming Zhang
Diagnostics 2023, 13(11), 1833; https://doi.org/10.3390/diagnostics13111833 - 23 May 2023
Cited by 4 | Viewed by 1570
Abstract
Background: Recently, anti-PD-1 antibodies plus lenvatinib has been administered in a series of solid tumors. Yet, the efficacy of chemo-free treatment of this combined therapy has seldom been reported in gallbladder cancer (GBC). The aim of our study was to initially evaluate the [...] Read more.
Background: Recently, anti-PD-1 antibodies plus lenvatinib has been administered in a series of solid tumors. Yet, the efficacy of chemo-free treatment of this combined therapy has seldom been reported in gallbladder cancer (GBC). The aim of our study was to initially evaluate the efficacy of the chemo-free treatment in unresectable GBCs. Methods: We retrospectively collected the clinical data of unresectable GBCs treated using chemo-free anti-PD-1 antibodies plus lenvatinib in our hospital from March 2019 to August 2022. The clinical responses were assessed, and PD-1 expression was evaluated. Results: Our study enrolled 52 patients, with the median progression-free survival being 7.0 months and the median overall survival being 12.0 months. The objective response rate was 46.2% and the disease control rate was 65.4%. The expression of PD-L1 in patients with objective response was significantly higher than those with progression of disease. Conclusions: For patients with unresectable GBC, when not eligible for systemic chemotherapy, chemo-free treatment using anti-PD-1 antibodies with lenvatinib may become a safe and rational choice. The expression of PD-L1 in tumor tissues may be correlated to the objective response, and thus is expected to be a predictor of efficacy, and further clinical studies are certainly needed. Full article
(This article belongs to the Special Issue Gallbladder Cancer: The Recent Progress)
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12 pages, 2643 KiB  
Article
Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients
by Ae Ri Ahn, Maryam Karamikheirabad, Min Su Park, Junyue Zhang, Hyun Sun Kim, Ji Su Jeong, Kyoung Min Kim, Ho Sung Park and Kyu Yun Jang
Diagnostics 2023, 13(6), 1149; https://doi.org/10.3390/diagnostics13061149 - 17 Mar 2023
Cited by 2 | Viewed by 1328
Abstract
Background: PAK4 and PHF8 are involved in cancer progression and are under evaluation as targets for cancer therapy. However, despite extensive studies in human cancers, there are limited reports on the roles of PAK4 and PHF8 in gallbladder cancers. Methods: Immunohistochemical expression of [...] Read more.
Background: PAK4 and PHF8 are involved in cancer progression and are under evaluation as targets for cancer therapy. However, despite extensive studies in human cancers, there are limited reports on the roles of PAK4 and PHF8 in gallbladder cancers. Methods: Immunohistochemical expression of PAK4 and PHF8 and their prognostic significance were evaluated in 148 human gallbladder carcinomas. Results: PAK4 expression was significantly associated with PHF8 expression in gallbladder carcinomas. Positive expression of nuclear PAK4, cytoplasmic PAK4, nuclear PHF8, and cytoplasmic PHF8 were significantly associated with shorter overall survival and relapse-free survival in univariate analysis. Multivariate analysis showed that nuclear PAK4 expression and nuclear PHF8 expression were independent predictors of overall survival and relapse-free survival in gallbladder carcinomas. Furthermore, coexpression of nuclear PAK4 and nuclear PHF8 predicted shorter overall survival (p < 0.001) and relapse-free survival (p < 0.001) of gallbladder carcinoma in multivariate analysis. Conclusions: This study suggests that the individual and coexpression patterns of PAK4 and PHF8 as the prognostic indicators for gallbladder carcinoma patients. Full article
(This article belongs to the Special Issue Gallbladder Cancer: The Recent Progress)
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