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Clinical Cancer Research : An Official... Dec 2022Gallbladder carcinoma (GBC) is an uncommon and aggressive disease, which remains poorly defined at a molecular level. Here, we aimed to characterize the molecular...
PURPOSE
Gallbladder carcinoma (GBC) is an uncommon and aggressive disease, which remains poorly defined at a molecular level. Here, we aimed to characterize the molecular landscape of GBC and identify markers with potential prognostic and therapeutic implications.
EXPERIMENTAL DESIGN
GBC samples were analyzed using the MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) platform (targeted NGS assay that analyzes 505 cancer-associated genes). Variants with therapeutic implications were identified using OncoKB database. The associations between recurrent genetic alterations and clinicopathologic characteristics (Fisher exact tests) or overall survival (univariate Cox regression) were evaluated. P values were adjusted for multiple testing.
RESULTS
Overall, 244 samples (57% primary tumors and 43% metastases) from 233 patients were studied (85% adenocarcinomas, 10% carcinomas with squamous differentiation, and 5% neuroendocrine carcinomas). The most common oncogenic molecular alterations appeared in the cell cycle (TP53 63% and CDKN2A 21%) and RTK_RAS pathways (ERBB2 15% and KRAS 11%). No recurrent structural variants were identified. There were no differences in the molecular landscape of primary and metastasis samples. Variants in SMAD4 and STK11 independently associated with reduced survival in patients with metastatic disease. Alterations considered clinically actionable in GBC or other solid tumor types (e.g., NTRK1 fusions or oncogenic variants in ERBB2, PIK3CA, or BRCA1/2) were identified in 35% of patients; 18% of patients with metastatic disease were treated off-label or enrolled in a clinical trial based on molecular findings.
CONCLUSIONS
GBC is a genetically diverse malignancy. This large-scale genomic analysis revealed alterations with potential prognostic and therapeutic implications and provides guidance for the development of targeted therapies.
Topics: Humans; Gallbladder Neoplasms; Mutation; Adenocarcinoma; Prognosis; Carcinoma, Neuroendocrine; Biomarkers, Tumor
PubMed: 36228155
DOI: 10.1158/1078-0432.CCR-22-1954 -
World Journal of Gastroenterology Nov 2015The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be... (Review)
Review
The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.
Topics: Carcinoma; Cholecystectomy; Gallbladder Neoplasms; Humans; Neoplasm Staging; Risk Factors; Treatment Outcome
PubMed: 26604631
DOI: 10.3748/wjg.v21.i43.12211 -
European Journal of Medical Research Feb 2019Neuroendocrine carcinoma (NEC) of gallbladder is a rare tumor. The clinical manifestation, treatment, and prognosis of gallbladder NEC are rarely reported. (Review)
Review
BACKGROUND
Neuroendocrine carcinoma (NEC) of gallbladder is a rare tumor. The clinical manifestation, treatment, and prognosis of gallbladder NEC are rarely reported.
CASE PRESENTATION
Eight gallbladder NEC patients were admitted into our hospital. The major complaint was right upper quadrant pain. Two patients underwent a radical resection of gallbladder and liver quadrate lobe. One of them underwent chemotherapies and had no recurrence of NEC during a 25-month followed-up period. The other patient did not undergo chemotherapies, and the NEC recurred in the patient 15 months afterwards. Two patients underwent a radical resection of gallbladder. One of them underwent chemotherapies and had an NEC recurrence 12 months afterwards. The other patient did not undergo chemotherapies and died due to the NEC recurrence 5 months after surgery. Three patients underwent a laparoscopic cholecystectomy and pathologic result showed gallbladder NEC. They did not undergo further treatment and no NEC recurrence was found. One patient underwent tumor biopsy and died due to obstructive jaundice 3 months afterwards. Pathologic results showed that all cases had positive chromogranin A and synaptophysin staining.
CONCLUSIONS
Gallbladder NEC showed no noticeably specific features, and the diagnosis relied on the pathological and immunohistochemistrical results. For T1N0M0 gallbladder NEC, cholecystectomy might be enough. For patients in a late stage, the management of combined therapies might be optimal.
Topics: Aged; Antineoplastic Agents; Carcinoma, Neuroendocrine; Cholecystectomy; Combined Modality Therapy; Female; Gallbladder Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local
PubMed: 30717775
DOI: 10.1186/s40001-019-0363-z -
Revista Medica de Chile Dec 2018Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age.
BACKGROUND
Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age.
AIM
To report the features of 15 patients with gallbladder epidermoid carcinoma.
MATERIAL AND METHODS
Review of medical records of patients with gallbladder cancer in an oncology service.
RESULTS
Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months.
CONCLUSIONS
Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.
Topics: Carcinoma, Squamous Cell; Female; Gallbladder Neoplasms; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Analysis
PubMed: 30848747
DOI: 10.4067/s0034-98872018001201438 -
Frontiers in Immunology 2023Programmed cell death (PCD) refers to cell death in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy... (Review)
Review
Programmed cell death (PCD) refers to cell death in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy and necrosis (programmed necrosis). Among these mechanisms, pyroptosis is mediated by the gasdermin family and is accompanied by inflammatory and immune responses. When pathogens or other danger signals are detected, cytokine action and inflammasomes (cytoplasmic multiprotein complexes) lead to pyroptosis. The relationship between pyroptosis and cancer is complex and the effect of pyroptosis on cancer varies in different tissue and genetic backgrounds. On the one hand, pyroptosis can inhibit tumorigenesis and progression; on the other hand, pyroptosis, as a pro-inflammatory death, can promote tumor growth by creating a microenvironment suitable for tumor cell growth. Indeed, the NLRP3 inflammasome is known to mediate pyroptosis in digestive system tumors, such as gastric cancer, pancreatic ductal adenocarcinoma, gallbladder cancer, oral squamous cell carcinoma, esophageal squamous cell carcinoma, in which a pyroptosis-induced cellular inflammatory response inhibits tumor development. The same process occurs in hepatocellular carcinoma and some colorectal cancers. The current review summarizes mechanisms and pathways of pyroptosis, outlining the involvement of NLRP3 inflammasome-mediated pyroptosis in digestive system tumors.
Topics: Humans; Carcinoma, Pancreatic Ductal; Digestive System; Esophageal Squamous Cell Carcinoma; Gallbladder Neoplasms; Inflammasomes; Neoplasms; Pyroptosis; Squamous Cell Carcinoma of Head and Neck; Stomach Neoplasms; Carcinoma, Hepatocellular; Colorectal Neoplasms
PubMed: 37081882
DOI: 10.3389/fimmu.2023.1074606 -
BMC Microbiology May 2022The microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports...
BACKGROUND
The microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports characterizing the bile microbiota are rare. This study aims to investigate the microbiota composition in patients with pancreaticobiliary cancers and benign diseases by 16S rRNA gene amplicon sequencing and to evaluate its potential value as a biomarker for the cancer of the bile duct, pancreas, and gallbladder.
RESULTS
We enrolled patients who were diagnosed with cancer, cystic lesions, and inflammation of the pancreaticobiliary tract. The study cohort comprised 244 patients. We extracted microbiome-derived DNA from the bile juice in surgically resected gallbladders. The microbiome composition was not significantly different according to lesion position and cancer type in terms of alpha and beta diversity. We found a significant difference in the relative abundance of Campylobacter, Citrobacter, Leptotrichia, Enterobacter, Hungatella, Mycolicibacterium, Phyllobacterium and Sphingomonas between patients without and with lymph node metastasis.
CONCLUSIONS
There was a significant association between the relative abundance of certain microbes and overall survival prognosis. These microbes showed association with good prognosis in cholangiocarcinoma, but with poor prognosis in pancreatic adenocarcinoma, and vice versa. Our findings suggest that pancreaticobiliary tract cancer patients have an altered microbiome composition, which might be a biomarker for distinguishing malignancy.
Topics: Adenocarcinoma; Gallbladder Neoplasms; Humans; Microbiota; Pancreatic Neoplasms; Prognosis; RNA, Ribosomal, 16S
PubMed: 35624429
DOI: 10.1186/s12866-022-02557-3 -
Journal of Medical Ultrasonics (2001) Apr 2021Endoscopic ultrasonography (EUS) has excellent spatial resolution and allows more detailed examination than abdominal ultrasonography (US) in terms of qualitative... (Review)
Review
Endoscopic ultrasonography (EUS) has excellent spatial resolution and allows more detailed examination than abdominal ultrasonography (US) in terms of qualitative diagnosis of tumors and evaluation of tumor invasion depth. To understand the role of EUS in gallbladder disease, we need to understand the normal gallbladder wall structure and how to visualize it on EUS. In addition, gallbladder lesions can be classified into two broad categories: protuberant and wall-thickening lesions. Here, the features on EUS were outlined. We also outlined the current status of EUS-FNA for gallbladder lesions as there have been scattered reports of EUS-FNA in recent years.
Topics: Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; Gallbladder; Gallbladder Diseases; Humans; Male; Middle Aged
PubMed: 32661803
DOI: 10.1007/s10396-020-01030-w -
Virchows Archiv : An International... Jun 2022Metastases to the gallbladder (GBm) are rare and pose a unique diagnostic challenge because they can mimic a second primary tumor. This study aimed to gain insight into... (Review)
Review
BACKGROUND
Metastases to the gallbladder (GBm) are rare and pose a unique diagnostic challenge because they can mimic a second primary tumor. This study aimed to gain insight into the clinicopathological and epidemiological characteristics of GBm.
METHODS
A comprehensive literature review was performed (literature cohort) and compared with a nationwide cohort of GBm patients diagnosed between 1999 and 2015 in the Netherlands, collected via two linked registries (population cohort). Overall survival (OS) was estimated by Kaplan-Meier. Hazard ratios were determined by a Cox proportional hazard model.
RESULTS
The literature cohort and population cohort consisted of 225 and 291 patients, respectively. In the literature cohort, melanoma was the most frequent origin (33.8%), while colorectal cancer was the most frequent origin in the population cohort (23.7%). Prognosis was poor with median OS ranging from 6.0 to 22.5 months in the literature and population cohorts, respectively. Age, timing of GBm (synchronous/metachronous) and primary tumor origin were independent prognostic factors for OS.
DISCUSSION
Metastases to the gallbladder are rare and carry a poor prognosis. Differences between both cohorts can be attributable to the biased reporting of tumor types that are more easily recognized as GBm because of distinct histological features.
Topics: Gallbladder; Humans; Melanoma; Neoplasms, Second Primary; Proportional Hazards Models; Retrospective Studies
PubMed: 35357569
DOI: 10.1007/s00428-022-03314-7 -
Archives of Pathology & Laboratory... Jun 2020The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated.
CONTEXT.—
The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated.
OBJECTIVE.—
To define the characteristics and prognostic significance of gallbladder or CD invasions in patients with DBDC.
DESIGN.—
Organ invasion patterns with clinicopathologic features were assessed in 258 resected DBDCs.
RESULTS.—
CD invasions (N = 31) were associated with frequent concomitant pancreatic and/or duodenal invasions (23 of 31, 74%) and showed stromal infiltration (16 of 31, 52%) and intraductal cancerization (15 of 31, 48%) patterns. In only 2 cases, invasions with intraductal cancerization were observed in the gallbladder neck. Conversely, all pancreatic (N = 175) and duodenal (83) invasions developed through stromal infiltration. CD invasions were associated with larger tumor size ( = .001), bile duct margin positivity ( = .001), perineural invasions ( = .04), and higher N categories ( = .007). Patients with pancreatic or duodenal invasions had significantly lower survival rates than those without pancreatic (median, 31.0 versus 93.9 months) or duodenal (27.5 versus 56.8 months, .001, both) invasions. However, those with gallbladder or CD invasions did not have different survival times ( = .13). Patients with concomitant gallbladder/CD and pancreatic/duodenal invasions demonstrated significantly lower survival rates than those without organ invasions ( .001).
CONCLUSIONS.—
Gallbladder invasions were rare in DBDCs as neck invasions with intraductal cancerization. CD invasions occurred by stromal infiltrations and intraductal cancerization, whereas all pancreatic and duodenal invasions had stromal infiltration patterns. Gallbladder and/or CD invasions did not affect survival rates of patients with DBDC, while pancreatic and duodenal invasions affected survival rates. Therefore, these differences in survival rates may originate from the different invasive patterns of DBDCs.
Topics: Aged; Bile Duct Neoplasms; Cholangiocarcinoma; Cystic Duct; Female; Gallbladder; Humans; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Survival Rate
PubMed: 31755778
DOI: 10.5858/arpa.2019-0218-OA -
Cancer Medicine Jan 2022Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative...
BACKGROUND
Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative frozen section during cholecystectomy is often performed to exclude the diagnosis of GBC. Our study is aiming to find a noninvasive indicator of XGC. To our knowledge, this is the largest XGC cohort ever studied.
METHODS
This study retrospectively collected clinical characteristics, serological tests, and imaging features of 150 GBC patients and 90 XGC patients. The diagnosis of these 150 GBC patients and 90 XGC patients was based on intraoperative frozen section histopathology. T-test was utilized to compare differences between XGC and GBC. Receiver operating characteristic (ROC) curve was conducted and the area under the curve (AUC) was managed to evaluate the validity.
RESULTS
The carcinoembryonic antigen (CEA) level in blood tests was significantly elevated in GBC patients than in XGC patients (p = 0.007). The presence of submucosal hypo-attenuated nodules (80% in XGC, 16% in GBC, p < 0.001), low density border (60% in XGC, 21% in GBC, p = 0.001), and nodular thickening in the bottom of the gallbladder with calcification (70% in XGC, 37% in GBC, p = 0.004) is significantly associated with XGC patients, whereas massive hilar infiltration (0% in XGC, 21% in GBC, p < 0.001), multiple lymph nodes in the hilar area (10% in XGC, 72% in GBC, p = 0.001), and gallbladder mucosal line continuity (50% in XGC, 95% in GBC, p = 0.002) are highly associated with GBC patients. The ROC curve was performed and the gallbladder mucosal line continuity (AUC = 0.708) and the AUC of low density border around the occupation (AUC = 0.654) showed a good prediction of XGC.
CONCLUSIONS
Gallbladder mucosal line continuity and low density border around the occupation presented good indication value for the diagnosis of XGC. Our study proposed a noninvasive differential diagnosis method for XGC and GBC.
Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers; Cholecystectomy; Cholecystitis; Diagnosis, Differential; Female; Gallbladder; Gallbladder Neoplasms; Humans; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Ultrasonography; Xanthomatosis
PubMed: 34837350
DOI: 10.1002/cam4.4442