HNF6 and HNF4α expression in adenocarcinomas of the liver, pancreaticobiliary tract, and gastrointestinal tract: an immunohistochemical study of 480 adenocarcinomas of the digestive system.

Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.

Survival benefit of adjuvant chemotherapy in patients with resected gallbladder adenocarcinoma: An updated retrospective cohort analysis.

BACKGROUND: The rarity yet high malignancy of gallbladder adenocarcinoma (GBA) endows it with a distinctive nature. Radical resection remains the foremost therapeutic approach for GBA, while the impact of early recurrence and metastasis on patient prognosis necessitates the utilization of adjuvant chemotherapy (AC). Despite numerous previous studies on this topic, a consensus regarding the authentic efficacy of AC has yet to be reached. METHODS: We conducted an updated retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2020 to explore the association between AC and survival outcomes in patients with resected GBA. RESULTS: Our study included 2782 patients from the SEER database, with further evaluation of 843 patients in each cohort following meticulous execution of a 1:1 propensity score matching. Remarkably, the AC cohort exhibited a significant survival advantage when juxtaposed against the non-AC cohort. Multivariable Cox regression analysis identified age at diagnosis, year at diagnosis, grade, AJCC T stage, AJCC N stage as well as AC as independent prognostic factors. Furthermore, our findings unveiled that poor/undifferentiated tumor histology, pathological T2 or higher category and pathological N1 category were significantly associated with improved survival when treated with AC while simultaneously observing improved survival across all age categories. CONCLUSION: These results provide additional evidence supporting the survival benefits of AC and offer guidance for personalized therapy in patients with resected GBA.

Metabolic parameters of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography for prognosis in patients with gallbladder adenocarcinoma: a cohort study.

Background: The incidence of gallbladder adenocarcinoma (GBA) is relatively low, yet it exhibits a high degree of malignancy and a significantly low 5-year survival rate. The aim of this study was to investigate the prognostic value of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography {2-[18F]FDG PET} parameters in predicting outcomes for patients with GBA. Methods: In total, 67 patients with GBA who underwent 2-[18F]FDG PET/computed tomography (CT) before treatment were retrospectively analyzed at Chinese PLA General Hospital from January 2012 to June 2022. All patients were diagnosed by pathology, and their baseline characteristics and clinical data were collected. The metabolic PET parameters of the primary and metastatic lesions were measured, including the maximum and average standardized uptake values (SUVs), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The prognostic significance of metabolic parameters and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to metabolic parameters were examined using the Kaplan-Meier method. Results: During a median follow-up period of 14.2 months, 43 patients (64.2%) experienced tumor recurrence or progression, and 38 patients (56.7%) died of cancer. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.007), distant metastases (P=0.049), tumor differentiation (P=0.028), surgery (P=0.014), carcinoembryonic antigen (CEA) level (P=0.030), carbohydrate antigen 19-9 (CA19-9) level (P=0.003), TLG (P=0.005), MTV (P<0.001), sum of the TLGs of the primary and metastatic lesions (total TLG, tTLG) (P=0.001), and sum of the MTVs of the primary and metastatic lesions (total MTV, tMTV) (P<0.001) were significant predictors of PFS. In multivariate analysis, MTV was an independent predictor of PFS [hazard ratio (HR) =2.785; 95% confidence interval (CI): 1.204-6.441; P=0.017]. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.027), distant metastases (P=0.036), tumor differentiation (P=0.047), surgery (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P=0.011), CEA level (P=0.036), CA19-9 level (P<0.001), TLG (P=0.007), MTV (P<0.001), tTLG (P=0.003), and tMTV (P<0.001) were significant predictors of OS. In the multivariate analysis, higher CA19-9 levels >37 U/mL and a greater tMTV (HR =2.961; 95% CI: 1.092-8.024; P=0.033) were predictive of OS. Conclusions: Our study results suggest that pretreatment 2-[18F]FDG PET parameters can not only assist in the diagnosis of patients with GBA but may also serve as predictive factors for the prognosis of these patients and should thus be applied in their treatment.

Distinguishing characteristics of xanthogranulomatous cholecystitis and gallbladder adenocarcinoma: a persistent diagnostic dilemma.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis which can resemble gallbladder adenocarcinoma (GAC) on preoperative imaging and present technical challenges in the performance of cholecystectomy. We examined our experience with each pathology to identify distinguishing characteristics that may guide patient counseling and surgical management. METHODS: A retrospective review of all pathologically confirmed cases of XGC and GAC following cholecystectomy between 2015 and 2021 at a single institution was performed. Clinical, biochemical, radiographic, and intraoperative features were compared. RESULTS: There were 37 cases of XGC and 20 cases of GAC. Patients with GAC were older (mean 70.3 years vs 58.0, p = 0.01) and exclusively female (100% vs 45.9%, p < 0.0001). There were no significant differences in accompanying symptoms between groups (nausea/vomiting, fevers, or jaundice). The mean maximum white blood cell count was elevated for XGC compared to GAC (16.4 vs 8.6 respectively, p = 0.044); however, there were no differences in the remainder of the biochemical profile, including bilirubin, liver transaminases, CEA, and CA 19-9. The presence of an intraluminal mass (61.1% vs 9.1%, p = 0.0001) and lymphadenopathy (18.8%. vs 0.0%, p = 0.045) were associated with malignancy, whereas gallbladder wall thickening as reported on imaging (87.9% vs 38.9%, p = 0.0008) and gallstones (76.5% vs. 50.0%, p = 0.053) were more often present with XGC. Cases of XGC more often had significant adhesions/inflammation (83.8% vs 55.0%, p = 0.03). CONCLUSION: Clinical features that may favor benign chronic cholecystitis over gallbladder adenocarcinoma include younger age, male gender, current or prior leukocytosis, and the absence of an intraluminal mass or lymphadenopathy. Laparoscopic cholecystectomy is a safe surgical option for equivocal presentations. Intraoperative frozen section or intentional staging of more extensive procedures based upon final histopathology are valuable surgical strategies.

Percutaneous cholecystostomy: an unusual route of dissemination of gallbladder carcinoma

A 78-year-old male with high-risk surgical presented severe acute cholecystitis and required cholecystostomy. The patient was referred later for assessment of the surgical treatment. A cholangio-MRI revealed a lesion on the gallbladder fundus with hepatic lesions suggestive of metastatic gallbladder carcinoma, which was confirmed in the histological analysis. The tumor progressed despite the chemotherapy through the cholecystostomy tract and developed peritoneal carcinomatosis. The patient did not respond to chemotherapy and he died 12 months later. (AU)

A Rare Case of Primary Adenocarcinoma of the Gallbladder With Lymphoid Stroma.

Adenocarcinoma of the gallbladder is the most common gallbladder carcinoma. But lymphoid stroma in gallbladder carcinoma is one of the rarest presentations. A unique case of gallbladder adenocarcinoma with lymphoid stroma in a 47-year-old female is presented in this report. The surgically resected gallbladder demonstrated invasive adenocarcinoma with lymphoid stroma, though it was radiologically diagnosed as xanthogranulomatous cholecystitis. Adenocarcinoma was immunohistochemically positive for pancytokeratin (AE1/AE3), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and carcinoembryonic antigen (CEA). Lymphoid stroma was positive for CD45, where B-cell zones were CD20 and CD79a positive, and T-cell zones were CD3 positive, with a larger T-cell subset being positive for CD4 than CD8. This is the fourth reported case of gallbladder adenocarcinoma with lymphoid stroma, which needs to be studied for pathogenesis, prognosis, and future therapy, if any.

Development and validation of an online dynamic prognostic nomogram for incidental gallbladder adenocarcinoma patients without distant metastasis after surgery: a population-based study.

Background: Gallbladder cancer is the most common malignant tumor of the biliary system, most of which is adenocarcinoma. Our study explored developing and validating a nomogram to predict overall and cancer-specific survival probabilities internally and externally for incidental gallbladder adenocarcinoma patients without distant metastasis after surgery. Methods: Patients screened and filtered in the Surveillance, Epidemiology, and End Results (SEER) database, whose years of diagnosis between 2010 and 2015 were collected as a derivation cohort, while those between 2016 and 2019 were a temporal validation cohort. Overall survival (OS) and cancer-specific survival (CSS) were chosen as the primary and secondary endpoints of the retrospective study cohort. Potential clinical variables were selected for a Cox regression model analysis by performing both-direction stepwise selection to confirm the final variables. The performance of final nomograms was evaluated by Harrell's C statistic and Brier score, with a graphical receptor operating characteristic (ROC) curve and calibration curve. Results: Seven variables of age, race, tumor size, histologic grade, T stage, regional lymph nodes removed, and positive regional lymph nodes were finally determined for the OS nomogram; sex had also been added to the CSS nomogram. Novel dynamic nomograms were established to predict the prognosis of incidental gallbladder adenocarcinoma patients without distant metastasis after surgery. The ROC curve demonstrated good accuracy in predicting 1-, 3-, and 5-year OS and CSS in both derivation and validation cohorts. Correspondingly, the calibration curve presented perfect reliability between the death or cancer-specific death probability and observed death or cancer-specific death proportion in both derivation and validation cohorts. Conclusion: Our study established novel dynamic nomograms based on seven and eight clinical variables separately to predict OS and CSS of incidental gallbladder adenocarcinoma patients without distant metastasis after surgery, which might assist doctors in advising and guiding therapeutic strategies for postoperative gallbladder adenocarcinoma patients in the future.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma: A propensity score-matched study.

BACKGROUND: Gallbladder mucinous adenocarcinoma (GBMAC) is a rare subtype of gallbladder adenocarcinoma (GBAC), with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis. AIM: To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field. METHODS: This study was conducted using data from the Surveillance, Epidemiology, and End Results database, including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017. The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts. In addition, propensity score matching (PSM) analysis was performed to balance the selection biases. Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). The Kaplan-Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients. RESULTS: The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC. They included a larger proportion of patients with unmarried status, advanced American Joint Committee on Cancer (AJCC) stage, higher T stage, higher N1 stage rate and lower N0 and N2 stage rates (P < 0.05). Multivariate analyses demonstrated that surgery [OS: Hazard ratio (HR) = 2.27, P = 0.0037; CSS: HR = 2.05, P = 0.0151], chemotherapy (OS: HR = 6.41, P < 0.001; CSS: HR = 5.24, P < 0.001) and advanced AJCC stage (OS: Stage IV: HR = 28.99, P = 0.0046; CSS: Stage III: HR = 12.31, P = 0.015; stage IV: HR = 32.69, P = 0.0015) were independent prognostic indicators for OS and CSS of GBMAC patients. Furthermore, after PSM analysis, there was no significant difference between GBMAC and matched typical GBAC patients regarding OS (P = 0.82) and CSS (P = 0.69). CONCLUSION: The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC. However, they show similar survival prognoses. Surgery, chemotherapy, and lower AJCC stage were associated with better survival outcomes. Further research is needed in the future to verify these results.

Circulating Tumor Cells are an Independent Risk Factor for Poor Prognosis in Patients with Gallbladder Adenocarcinoma.

BACKGROUND: The study aimed to evaluate the prognostic impact of circulating tumor cells (CTCs) in patients with gallbladder adenocarcinoma after resection. MATERIALS AND METHODS: Between January 2018 and January 2021, 101 consecutive patients with gallbladder adenocarcinoma were included. CTCs were detected and enumerated using the CanPatrol® technique. The follow-up period ended in January 2023. The cancer-specific survival (CSS) and disease-free survival (DFS) were calculated using log-rank and Cox regression analyses. RESULTS: CTCs were detected positively in 61.54% (8/13) of the patients in the non-operation group and 13.64% (12/88) in the operation group. In the operation group, the median CSS for CTCs-positive and CTCs-negative patients was 5.0 and 9.5 months (P < 0.001), respectively, and DFS was 2.8 and 5.0 months at stage III (P < 0.001), respectively. In the non-operation group, the median CSS for CTCs-positive and CTCs-negative patients was 3.5 and 6.5 months (P = 0.0031), respectively. The median CSS for CTCs-positive patients in the operation group was similar to that in the non-operation group (P = 0.67). Multivariate analyses showed that positive CTCs was an independent risk factor for poor CSS (HR 0.066, 95% CI 0.021-0.206, P < 0.001) as well as lymph infiltration (HR 0.320, 95% CI 0.110-0.930, P = 0.036), without R0 curative resection (HR 7.520, 95% CI 2.100-26.931, P = 0.002), and without adjuvant chemotherapy (HR 7.730, 95% CI 2.416-24.731, P < 0.001). CONCLUSION: Positive CTCs was an independent predictor of poor prognosis after resection in patients with gallbladder adenocarcinoma. Preoperative detection of CTCs may play an important guiding role in formulating treatment strategies for these patients.

Comparison of carcinosarcoma and adenocarcinoma of the gallbladder: a study based on SEER population for propensity matching and nomogram analysis.

BACKGROUND: Carcinosarcoma of the gallbladder (CSGB) is an uncommon malignancy, and limited literature is available on its clinicopathological features, prognosis, and treatment options. METHODS: Using the SEER database, we selected 7634 gallbladder adenocarcinoma patients (diagnosed from 2004 to 2015) and 58 carcinosarcoma of the gallbladder patients (diagnosed from 1988 to 2019) based on predetermined criteria. We compared the overall survival (OS) and cancer-specific survival (CSS) before and after propensity score matching in two groups. Cox univariate and multivariate analyses were performed, and a nomogram was further generated to investigate the impact of clinical and pathological variables on the survival of patients with CSGB. Finally, we evaluated the effect of different treatment modalities on the overall survival of CSGB patients. RESULTS: Notably, CSGB patients had larger tumors and underwent surgery more frequently than gallbladder adenocarcinoma patients, with lower rates of deeper tumor infiltrates, and lymph node infiltrates. Conversely, gallbladder adenocarcinoma patients had a higher proportion of AJCC staging (III-IV). Despite these differences, no significant differences were found in OS and CSS between the two groups before and after propensity score matching. For CSGB patients, AJCC staging, surgery and tumor size were significant prognostic factors, while treatment modalities such as surgery combined with chemotherapy, or combined radiochemotherapy, as well as radical resection, did not significantly prolong patient survival. CONCLUSION: No significant difference was found in survival rates between CSGB and gallbladder adenocarcinoma patients, while radical surgery and different combined treatment modalities did not provide significant survival benefits.

Immunotherapy in Biliary Tract Cancers: Current Standard-of-Care and Emerging Strategies.

Biliary tract cancers (BTCs), comprising intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder adenocarcinoma, continue to be challenging to manage. Conventional chemotherapy regimens for advanced disease are limited in both options and benefits, and more effective perioperative regimens are also needed. Over the last decade, immunotherapy has had a profound impact on the management of many solid tumor types, particularly in using immune checkpoint inhibition to enable a tumor-directed T cell response. Immunotherapy administered on its own has had limited utility in BTCs, in part due to a hostile immune microenvironment and the relative infrequency of biomarker-based tumor-agnostic indications for immunotherapy. However, immunotherapy in conjunction with chemotherapy, molecularly targeted therapies, and/or anti-angiogenic therapies has gained traction, supported by evidence that these agents can impart favorable immunomodulatory effects on the tumor microenvironment. The TOPAZ-1 trial led to the first BTC-specific immunotherapy approval, establishing the combination of durvalumab with gemcitabine and cisplatin as the preferred first-line treatment for advanced or metastatic disease. Recently, the KEYNOTE-966 trial showed positive results for the combination of pembrolizumab with gemcitabine and cisplatin in the same setting, adding further evidence for the addition of immune checkpoint inhibition to the standard chemotherapy backbone. Meanwhile, advances in the molecular profiling of BTCs has contributed to the recent proliferation of molecularly targeted therapeutics for the subset of BTCs harboring alterations in IDH1, FGFR2, MAP kinase signaling, HER2, and beyond, and there has been great interest in investigating combinations of these agents with immunotherapy. Emerging immunotherapy strategies beyond immune checkpoint inhibition are also being studied in BTCs, and these include immunostimulatory receptor agonists, Wnt signaling modulators, adoptive cell therapy, and cancer vaccines. A large number of trials are underway to explore promising new combinations and immune-targeted strategies, offering opportunities to expand the role of immunotherapy in BTC management in the near future.

Lymph node metastatic status could predict the prognosis of intracholecystic papillary neoplasm of gallbladder.

Intracholecystic papillary neoplasm (ICPN) is a non-invasive epithelial tumor that presents as a grossly identifiable mass arising in the mucosa and protruding into the lumen. ICPN is associated with invasive carcinoma. There are few studies on the clinicopathological features of ICPN, including that with invasive carcinoma. We evaluated the clinicopathological characteristics of 42 ICPNs and 41 conventional gallbladder adenocarcinomas (cGBAs). Subserosa or deeper (≥ss) invasion was significantly lower in ICPN (61.9%) than that in cGBA (90.2%) (P = 0.004). Cox regression analysis revealed that lymph node metastasis (hazard ratio [HR] [95% confidence interval (CI)]: 2.610 [1.131, 6.024], P = 0.025) and positive margin (HR [95% CI]: 5.143 [2.113, 12.516], P < 0.001), but not ≥ss invasion (HR [95% CI]: 1.541 [0.479, 4.959], P = 0.469), were independent prognostic factors. In addition, there was a significant interaction between histological type and lymph node metastasis (HR [95% CI]: 0.191 [0.042, 0.983], P = 0.033). In cGBA, the presence or absence of lymph node metastasis did not affect prognosis; however, ICPN without lymph node metastasis had better prognosis. Therefore, the histological classification of ICPN and cGBA and the pathological evaluation of lymph node metastasis in ICPN are crucial for determining prognosis.

Synchronous Liver Abscess With Cholecystitis: A Rare Case of Initial Presentation of Gallbladder Cancer Posing a Diagnosis Challenge.

Gallbladder carcinoma (GBC) is the most common of all biliary tract cancers. GBC is a multifactorial disease. Gallbladder dysplasia from any gallbladder inflammatory condition is one of the main risk factors for GBC. The late diagnosis of GBC is a major problem in its treatment. It is treated by radical resection and the prognosis is improved by adjuvant chemoradiation. We present a rare case of gall bladder cancer presenting as hepatic abscesses with severe sepsis. An 83-year-old male presented with progressive symptoms of shakiness, general weakness, vomiting, and profuse diarrhea. Lab work revealed deranged liver enzymes. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) abdomen revealed intrahepatic abscesses contiguous with the gallbladder lumen through a gallbladder wall defect and cholecystitis of unknown chronicity. Subsequently, he underwent central hepatectomy and the pathology report of the sample as well as endoscopic retrograde cholangiopancreatography (ERCP) brushings revealed gallbladder adenocarcinoma. The case was complicated by biloma, acute renal failure, and the development of malignant ascites, and the patient died almost four months after the diagnosis of gallbladder cancer.

Comparison of clinicopathological characteristics of mucinous adenocarcinoma and conventional adenocarcinoma of gallbladder.

BACKGROUND: Gallbladder mucinous adenocarcinoma (GBMAC) is a rare type of gallbladder malignant tumor, whereas little is known regarding the clinicopathological features and surgical outcomes of GBMAC. METHODS: From January 2000 till December 2015, 54 GBMAC patients who underwent curative-intent surgical resection at our institution were retrospectively reviewed. We compared the clinicopathological features and surgical outcomes of these GBMAC patients with a relatively large cohort of surgically resected conventional gallbladder adenocarcinoma (GBAC) patients without existence of mucinous components. RESULTS: The clinicopathological features of GBMAC were significantly different from conventional GBAC, including poorer tumor differentiation (P < 0.001), higher CA19-9 levels (P < 0.001), larger tumor sizes (P = 0.020), advanced AJCC tumor stage (P = 0.002), higher frequency of liver parenchyma invasion (P = 0.020), portal vein invasion (P = 0.003), lymph node metastasis (P = 0.016), lympho-vascular invasion (P < 0.001) and perineural invasion (P = 0.025). Relative to conventional GBAC patients, GBMAC patients showed significantly worse overall survival (OS) (29.0 vs 15.0 months; P < 0.001). Multivariate analysis confirmed the surgical margin (P = 0.046), tumor differentiation grade (P = 0.018), lymph node metastasis (P = 0.024), and presence of signet-ring cell component (P = 0.005) as independent prognostic factors influencing OS of patients with GBMAC. CONCLUSION: GBMAC always had more aggressive biological behaviors and poor survival outcomes even after curative surgery. GBMAC patients with the presence of signet-ring cell component showed even worse survival outcome.

Adenocarcinoma de vesícula biliar: una entidad poco frecuente y mortal. A propósito de un caso / Gallbladder adenocarcinoma: a rare and fatal entity. A case report

Introducción: El adenocarcinoma de vesícula biliar es de las neoplasias digestivas con peor pronóstico; es poco común, y está asociado a una alta mortalidad. La mayoría de los diagnósticos son incidentales cuando se realiza exploración quirúrgica por sospecha de colelitiasis; encontrando malignidad en el 1 a 2% de estos casos. Produce síntomas inespecíficos, llevando a diagnósticos tardíos, empeorando así el pronóstico. Las características de esta neoplasia y el diagnóstico tardío hacen que muchas veces la resección curativa no sea posible. Caso Clínico : Paciente femenino de 45 años, quien refiere inicio de enfermedad actual (IEA) en diciembre de 2021 cuando posterior a ingesta de comida presenta dolor de aparición súbita, opresivo, de fuerte intensidad en epigastrio, intermitente. Ultrasonido abdominal (USA) reporta LOE vesicular. Se decide resolución mediante colecistectomía abierta extendida, donde se encuentra vesícula biliar (VB), con tumor en su interior que ocupa 30% de la luz, se realiza biopsia intraoperatoria, diagnosticándose ADC de vesícula. La paciente evolucionó satisfactoriamente y es egresada. En controles periódicos no hay evidencia de recidiva de la enfermedad. Conclusión : El cáncer de vesícula biliar (CVB) es una patología poco común, de difícil diagnóstico y asociado a una alta tasa de mortalidad, que produce síntomas inespecíficos por lo que es necesario un alto índice de sospecha para su diagnóstico. El manejo y conducta terapéutica depende de la extensión y el estadiaje del tumor. Es necesaria la realización de más estudios para determinar y estandarizar el manejo de esta infrecuente neoplasia(AU)

Introduction: Gallbladder adenocarcinoma is one of the digestive neoplasms with the worst prognosis; it is uncommon and is associated with high mortality. Most diagnoses are incidental when surgical exploration is performed due to suspected cholelithiasis, with malignancy found in 1 to 2% of these cases. It produces nonspecific symptoms, leading to late diagnoses, thereby worsening the prognosis. The characteristics of this neoplasm and the late diagnosis often make curative resection impossible.Clinical Case : A 45-year-old female patient who reported the onset of the current illness in December 2021. After a meal, she experienced sudden, intense, and intermittent epigastric pain. Abdominal ultrasound (US) reported gallbladder wall thickening. It was decided to perform an extended open cholecystectomy, and a tumor was found inside the gallbladder, occupying 30% of its lumen. An intraoperative biopsy was performed, diagnosing gallbladder adenocarcinoma. The patient recovered satisfactorily and was discharged. Subsequent follow-up visits have shown no evidence of disease recurrence.Conclusion : Gallbladder cancer (GBC) is a rare condition with a challenging diagnosis and a high mortality rate. It produces nonspecific symptoms, so a high index of suspicion is necessary for its diagnosis. The management and therapeutic approach depend on the tumor's extent and staging. Further studies are needed to determine and standardize the management of this uncommon neoplasm(AU)

Gallbladder adenocarcinomas undergo subclonal diversification and selection from precancerous lesions to metastatic tumors.

We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was ERBB2 and TP53 (54.5%), followed by FBXW7 (27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia [BilIN]), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as SMAD4, ROBO1, and DICER1. In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.

A Case of Gallbladder Adenocarcinoma Presenting as Mirizzi Syndrome in a Non-Jaundiced Patient With Recent Weight Loss.

There are many different types of gallbladder diseases, mainly resulting from inflammation. The long-term presence of an insult to the gallbladder leads to chronic inflammation, which is a nidus for complications such as Mirizzi syndrome and gallbladder cancer, both of which can become mimics of one another. Preoperative diagnosis of either gallbladder cancer or Mirizzi syndrome is often difficult, leading to late diagnosis and complicating the patient's treatment course. We report a case of a 65-year-old male who presented with abdominal pain and significant weight loss, with no physical evidence of jaundice and normal liver function. This was initially diagnosed as acute cholecystitis and Mirizzi syndrome before being diagnosed as gallbladder adenocarcinoma on final histology.

Low expression of DUSP4 expression predicts unfavorable prognosis in gallbladder adenocarcinoma.

Background: Dual specificity phosphatase 4 (DUSP4), which regulates the mitogen activated protein kinases, has emerged as a tumor suppressor gene in several human malignancies. Aims and Objectives: In this study, we investigated the clinicopathologic significance and the prognostic role of DUSP4 in gallbladder adenocarcinoma. Materials and methods: DUSP4 expression was evaluated immunohistochemically in tissue microarray from 110 gallbladder adenocarcinoma samples and scored by H score system. The cut off (H score <170) was determined by ROC curve analysis. Results: Low expression of DUSP4 expression was observed in 57 (51.8%) out of 110 gallbladder adenocarcinoma samples. Low expression of DUSP4 expression was significantly associated with high histologic grade (P = 0.017), high pT stage (P = 0.002) and high AJCC stage (P = 0.007). Kaplan Meier survival curves revealed that patients with low expression of DUSP4 expression had significantly worse cancer specific survival (P = 0.024, log rank test). However, there was no significant association between DUSP4 expression and recurrence free survival. Conclusions: In conclusion, gallbladder adenocarcinoma with low expression of DUSP4 expression was associated with adverse clinicopathologic characteristics and poor patient outcome.patient outcome.

FDG PET-MRI evaluation of synchronous gallbladder adenocarcinoma and POEMS syndrome.

POEMS syndrome is a rare paraneoplastic syndrome associated with a plasma cell proliferative disorder. Gallbladder adenocarcinoma is a rare malignancy, with no association with POEMS syndrome. The plasma cell dyscrasia is routinely evaluated with advanced hybrid imaging to assess both anatomic and functional components. We present a case of a 59-year-old female with a known diagnosis of POEMS syndrome who underwent a whole-body restaging evaluation with hybrid positron emission tomography (PET) and magnetic resonance imaging (MR) to restage her plasma cell dyscrasia. She also had a prior diagnosis of gallbladder adenocarcinoma. Our case focuses on the value of PET/MR in this scenario as well as a rare case of osseous metastasis from gallbladder carcinoma.