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Introduction: Gallbladder cancer (GBC) is a rare and aggressive hepatobiliary malignancy with poor prognosis. The symptoms of GBC are insidious and non-specific in its early stages, and most patients are diagnosed at advanced or late stages. Surgical resection is the only potentially curative treatment for GBC for select patients. There is a lack of robust data for patients with GBC, leading to heterogenous practices in management strategies and outcomes. In this study, we aimed to identify patient characteristics and cumulative overall survival (OS) in patients with GBC who underwent surgical resection with curative intent. Methods: All adult patients (age ≥18 years) with localized or locoregionally advanced GBC who underwent definitive surgery with curative intent at our tertiary institution between 1/2013 and 12/2023 were retrospectively identified. Clinical, laboratory, radiology, histopathology, treatment, and survival data were collected from electronic medical records. Postoperative data included the use of adjuvant chemotherapy or radiotherapy, and patient survival mortality at a cut-off date of 1 February, 2024, calculated from the date of curative surgery. Continuous variables are reported as median and quartile 1 (Q1) and quartile 3 (Q3), while categorical variables are reported as counts and percentages. Results: A total of 94 patients with GBC were included in the study. Median age was 71 (62–77) years and 58 (61.7%) patients were female. Median tumor size was 3.3 (1.9–5.0) cm. Perineural invasion was seen in 48.9% and vascular invasion in 38.3% of patients. A positive surgical margin was present in 50% of the patients, and incidental GBC (IGBC) was seen in 48.9% of patients. Tumor grade was well differentiated in 7.6%, moderately differentiated in 53.3%, and poorly differentiated in 39.1% of the patients. Patients with stage T1a (2.1%) and T1b (11.7%) tumors comprised the minority, and the majority of the tumors were stage T2 (55.3%), followed by T3 (31.9%). A total of 60.6% of patients with GBC underwent adjuvant chemotherapy, and 17% underwent adjuvant radiotherapy after surgical resection. Overall, 62 (66.0%) patients died, and the median OS was 1.88 years. The 1-year OS was 68.7%, 3-year OS was 37.4%, and 5-year OS was 32.2%. A higher absolute median OS was seen in patients who had adjuvant chemotherapy (2.1 years) compared to no chemotherapy (1.9 years); however, this finding was not statistically significant (p = 0.36). The median survival was 2.3 years in IGBC compared to 1.6 years in non-IGBC (p = 0.63). Conclusions: GBC is an aggressive hepatobiliary malignancy that is often diagnosed at advanced stages. Our study showed high rates of local and systemic involvement and high mortality, and the need for prospective and randomized studies on adjuvant therapies to assess their survival benefit. Real-world patient data remain important to identify patients at risk of worse outcomes and to stratify risks prior to surgery. [ABSTRACT FROM AUTHOR]

The skin is one of the largest organs of the human body; however, cutaneous metastases are occasional.1 The overall incidence of cutaneous metastasis due to malignancies is 5.3%.1,2 The most common cutaneous metastases are associated with breast cancer, followed by lung, colorectal, renal, ovarian, and bladder malignancies.2,3 Gall bladder carcinoma (GBC) accounts for 80-95% of biliary tract malignancies and carries a poor prognosis.2,3 Most patients remain asymptomatic until the tumor reaches an advanced stage or is incidentally diagnosed. Primary gallbladder carcinoma spread by direct extension and metastasis. By direct extension, the liver is the most usually affected organ, with an incidence of 60 to 90%, while regional lymph nodes are involved in approximately 60% of cases. Extra-abdominal metastasis is rare and is disseminated through vascular dispersion and tumor cell homing. Cutaneous metastasis of primary gallbladder cancer is sporadic and has an incidence of 0.7 to 0.9%.4 GBC prevalence varies geographically and racially. The indigenous Mapuche people of Chile have the greatest incidence, with 27.3 per 100,000 person-years documented among females. High rates have also been discovered in regions of India, eastern Asia, and various central and eastern Europe countries. GBC is more common in females with gallstones in Chile and India. It is virtually equally common in men in Eastern Asia, although the link to gallstones is significantly weaker, implying regional etiological differences.2-4 Gallbladder carcinomas diagnosed at an advanced age carry a poor prognosis.1,2 The bile ducts, stomach, duodenum, colon, omentum, abdominal wall, pancreas, and portal vein are involved by direct extension.2 Extra abdominal metastases, vascular dissemination, and tumor cell homing are rare. The lung is the most common extra-abdominal site of metastases. Other rare sites of metastases include the heart, orbit, central nervous system, skin, and bone.3,4 Nevertheless, metastases to the scalp have not been fully clarified. According to Paget's “soil-seed” hypothesis, the scalp provided a favorable environment for colonizing and surviving gallbladder cancer cells. In addition, the interaction between tumor cells and certain factors secreted from the dermis or epidermis might be extensively involved in the skin (including the scalp) homing mechanism of metastatic cells.2,3 The five-year survival rate among patients diagnosed with gallbladder cancer is

Schmincke described lymphoepithelioma as an undifferentiated carcinoma with abundant lymphoid stroma in the nasopharynx. Tumors with a similar histomorphology in extrapharyngeal areas have been referred to as lymphoepithelioma-like carcinoma (LELC). The association of an Ebstein-Barr virus (EBV) infection with lymphoepithelioma is well established in the nasopharynx but not so well at the extrapharyngeal sites. Only four cases of LELC have been reported in the gall bladder, of which all were negative for the EBV. This paper reports the first case of an EBV-associated mixed gall bladder carcinoma exhibiting a distinct phenotype of LELC and adenocarcinoma with mucinous differentiation. The EBV was confirmed by the strong granular membranous and cytoplasmic expression of LMP-1 (latent membrane protein-1) on immunohistochemistry and nuclear EBER RNA on chromogen in-situ hybridization in the tumor. This is the first case of LELC positive for EBV in the gall bladder. LELC has a more favorable prognosis than conventional adenocarcinoma or squamous cell carcinoma, irrespective of the site. Although a higher T stage and nodal metastasis were exceptional in the present case in contrast to the previous cases, the EBV-associated lymphocytic response might limit the disease spread and confer better overall survival and prognosis in these patients. Nevertheless, more prospective studies with a larger cohort will be needed to understand the pathogenesis, biological behavior, and prognosis of this rare entity.

Sarcomatoid carcinoma is rarely diagnosed as gallbladder cancer. Its aggressive nature, due to the characteristics of both sarcoma and carcinoma, results in a poor prognosis. We report a case of gallbladder sarcomatoid carcinoma in an 82-year-old male who was referred to our hospital for evaluation of gallbladder cancer observed on abdominopelvic computed tomography. The characteristics of the cancer were not confirmed after several imaging modalities. The surgically resected tumor was positive for both cytokeratin and vimentin as revealed via immunohistochemical staining, and a sarcomatoid carcinoma was finally diagnosed. The role of chemotherapy has not yet been identified. Therefore, radiation therapy is planned to reduce the risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of Twist1 on invasion and metastasis of gallbladder carcinoma cells and the regulation of Bmi1, E-Cadherine andN-Cadherine. Methods Twist1 shRNA lentivirus vector was constructed to infect GBC-SD cells as the experimental group. The empty lentivirus-infected GBC-SD cells were the negative group, and the untreated GBC -SD cells were the blank group. Cell migration and invasion ability were detected by cell scratch and Transwell chamber invasion assay. Western blot and RT-PCR were used to detect the relative expression levels of Twist1, Bmi1, E-Cadherine and N-Cadherine. Results Compared with the negative and blank groups, the experimental group had a lower cell scratch healing degree and fewer invasion numbers (P < 0.000 1). There was no significant difference in cell migration rate and invasion number between the two control groups (P > 0.05). The relative expression levels of Twist1, Bmi1 and N-Cadherine in the negative group and blank group were obviously higher than those in the experimental group (P < 0.001). The relative expression levels of E-Cadherine protein and mRNA were obviously lower than those of the experimental group (P < 0.000 1). There was no significant difference in the relative expression levels of protein and mRNA between the negative group and the blank group (P > 0.05). Conclusion Targeted silencing of Twist1 can inhibit the migration and invasion of gallbladder carcinoma cells, and the mechanism may be related to inhibiting the expression of Bmi1 and the process of epithelial-mesenchymal transformation. [ABSTRACT FROM AUTHOR]

Summary: Previous studies have explored the role of laparoscopic surgery (LS) in the surgical management of gallbladder carcinoma (GBC) and obtained satisfactory outcomes versus conventional open surgery. However, most of them either included a small number of patients or mainly focused on the early-staged lesions. Therefore, their results were less statistical powerful and a more comprehensive evaluation on the role of LS in GBC is warranted. A thorough database searching was performed in PubMed, EMBASE and Cochrane Library for comparative studies between the laparoscopic and open approach in the surgical management of GBC and 18 comparative studies were finally identified. RevMan 5.3 and Stata 13.0 software were used for statistical analyses. Pooled results revealed that patients in the laparoscopic group recovered faster with less intraoperative hemorrhage and less postoperative morbidity. Comparable operative time, overall recurrence rate, R0 resection rate, lymph node yield, intraoperative gallbladder violation rate and postoperative survival outcomes were also acquired. Regarding the debating issue of port-site recurrence, a significantly higher incidence of port-site recurrence was observed in laparoscopic group. However, having excluded studies on incidental gallbladder carcinoma, the subsequent pooled result showed no significant difference. Considering the inherent inconsistency of the surgical indication between laparoscopic and open surgeries and the deficiency of advanced lesions, we drew a conclusion that laparoscopic surgery seems to be only safe and feasible for early- or middle-staged lesions. Upcoming random controlled trials or comparative studies with equivalent surgical indication focused on advanced lesions are warranted for further evaluation.

A 75‑year‑old male with head‑and‑neck squamous cell cancer received a staging f‑18‑fluorodeoxyglucose (18F‑FDG) positron emission tomography‑computed tomography (PET/ CT) scan which showed additional focal abnormal uptake in the right hepatic lobe. The patient was treated for probable metastatic disease. Restaging FDG PET/CT scan revealed resolution of uptake in the head‑and‑neck and persistent focal uptake in the presumed liver metastasis. An abdominal CT with intravenous contrast revealed an enhancing mass in the gallbladder, without extension into the liver. Cholecystectomy revealed an intracholecystic papillary neoplasm of the gallbladder. The initial appearance of hepatic metastasis was due to a misregistration artifact. [ABSTRACT FROM AUTHOR]

Background: Sequential extended cholecystectomy (SEC) is currently recommended for T2 and higher gallbladder cancer (GBC) diagnosed after simple cholecystectomy (SC), but the value and timing of re-resection has not been fully studied. We evaluated the long-term oncologic outcomes of T2 GBC according to the type of surgery performed and investigated the optimal timing for SEC.Methods: Patients diagnosed with T2 GBC who underwent SC, extended cholecystectomy (EC), or SEC between 2002 and 2017 were retrospectively reviewed. Those who underwent other surgical procedures or those with incomplete medical records were excluded. Overall survival (OS) and disease-free survival (DFS) according to the types of surgeries and prognostic factors for OS and DFS were analyzed. Survival analysis was done between groups that were divided according to the optimal cutoff time interval between SC and SEC based on DFS data.Results: Of the 226 T2 GBC patients, 53, 173, and 44 underwent SC, EC, and SEC, respectively. The 5-year OS rate was 50.1%, 73.2%, and 78.7%, and the DFS rate was 46.8%, 66.3%, and 65.2% in the SC, EC, and SEC groups, respectively. EC (p = 0.001 and p = 0.001) and SEC (p = 0.007 and p = 0.065) groups had better 5-year OS and DFS rates than the SC group. Preoperative CA 19-9 level > 37 U/mL (HR 1.56; 95% CI 1.87-2.79; p < 0.001) and N1 stage (HR 2.88; 95% CI 1.76-4.71; p < 0.001) were associated with poorer prognosis. The optimal cutoff interval between SC and SEC was 28 days. Patients who underwent SEC ≤ 28 days after the initial cholecystectomy had better 5-year DFS rates than patients who underwent SEC after > 28 days (75.0% vs. 52.8%, p = 0.023).Conclusions: SEC is recommended for T2 GBC diagnosed after SC, because SEC provides better survival outcomes than SC alone. A time interval of less than 28 days to SEC is associated with an improved DFS. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic cholecystectomy (LC) is one of the most performed general surgeries. Incidental gallbladder carcinoma (IGBC) is diagnosed in 0.3-2.9% of all cholecystectomies and accounts for most detected gallbladder cancers (GBCs). This study aims to evaluate the incidence, clinical, and prognostic features of IGBC diagnosed after LC for benign gallbladder disease. Materials and Methods: We performed a retrospective analysis of patients who underwent cholecystectomy between January 2016 and October 2021 at the Istanbul Sultanbeyli State Hospital General Surgery Clinic. Data regarding the demographics, pathological features of the tumors, and survival times of patients were examined. Results: A total of 745 patients were analyzed. The patients' median age was 43 (18-78), and the male-to-female ratio was 137:608. Four patients were diagnosed with gallbladder carcinoma after LC; however, one patient had pre-operative suspicious GBC. Three patients were diagnosed with IGBC. The cancer stages and survival times of the IGBC patients were pT2, pT2, and pT1a and 8, 34, and 40 months, respectively. Conclusion: Most GBCs are detected incidentally. The most signifcant factor determining the progno- sis is an early stage detection. To detect IGBC, cholecystectomy specimens must be carefully examined histopathologically. [ABSTRACT FROM AUTHOR]

Background and purpose: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. Methods: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). Results: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. Conclusion: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. Protocol registration: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/). [ABSTRACT FROM AUTHOR]

Traumatic neuroma mostly results from nerve injury caused by surgery or trauma. Traumatic neuroma of the gallbladder without prior abdominal surgery is extremely rare, and we termed it “idiopathic traumatic neuroma of the gallbladder.” Due to its rarity and a lack of specific clinical and radiological features, it is most commonly misdiagnosed. In our case, the patient was admitted to our hospital for cholangiocarcinoma. Repeated abdominal contrast-enhanced computed tomography scans preoperatively indicated hilar cholangiocarcinoma. Due to insufficient future liver remnant, we planned preoperative percutaneous transhepatic cholangiodrainage and percutaneous transhepatic portal vein embolization based on multidisciplinary team consultation. The patient was then admitted 1 month later for surgery. We performed a laparoscopic cholecystectomy and an extensive laparoscopic right hepatectomy as gallbladder carcinoma was strongly suspected intraoperatively. However, the final diagnosis was traumatic neuroma of the gallbladder confirmed by pathological examination. Traumatic neuroma of the gallbladder is very rare, and we hope to provide some references for diagnosis by reporting our case and reviewing the literature on this topic so that extensive treatment can be avoided, thus improving patients’ quality of life. To the best of our knowledge, this is the first reported case of traumatic neuroma without prior surgery in the English literature since 1996.

Previous studies have explored the role of laparoscopic surgery (LS) in the surgical management of gallbladder carcinoma (GBC) and obtained satisfactory outcomes versus conventional open surgery. However, most of them either included a small number of patients or mainly focused on the early-staged lesions. Therefore, their results were less statistical powerful and a more comprehensive evaluation on the role of LS in GBC is warranted. A thorough database searching was performed in PubMed, EMBASE and Cochrane Library for comparative studies between the laparoscopic and open approach in the surgical management of GBC and 18 comparative studies were finally identified. RevMan 5.3 and Stata 13.0 software were used for statistical analyses. Pooled results revealed that patients in the laparoscopic group recovered faster with less intraoperative hemorrhage and less postoperative morbidity. Comparable operative time, overall recurrence rate, R0 resection rate, lymph node yield, intraoperative gallbladder violation rate and postoperative survival outcomes were also acquired. Regarding the debating issue of port-site recurrence, a significantly higher incidence of port-site recurrence was observed in laparoscopic group. However, having excluded studies on incidental gallbladder carcinoma, the subsequent pooled result showed no significant difference. Considering the inherent inconsistency of the surgical indication between laparoscopic and open surgeries and the deficiency of advanced lesions, we drew a conclusion that laparoscopic surgery seems to be only safe and feasible for early- or middle-staged lesions. Upcoming random controlled trials or comparative studies with equivalent surgical indication focused on advanced lesions are warranted for further evaluation. [ABSTRACT FROM AUTHOR]

Abstract Background Cancer-associated fibroblasts (CAFs) and vasculogenic mimicry (VM) play important roles in the occurrence and development of tumors. However, the relationship between CAFs and VM formation, especially in gallbladder cancer (GBC) has not been clarified. In this study, we investigated whether gallbladder CAFs (GCAFs) can promote VM formation and tumor growth and explored the underlying molecular mechanism. Methods A co-culture system of human GBC cells and fibroblasts or HUVECs was established. VM formation, proliferation, invasion, migration, tube formation assays, CD31-PAS double staining, optic/electron microscopy and tumor xenograft assay were used to detect VM formation and malignant phenotypes of 3-D co-culture matrices in vitro, as well as the VM formation and tumor growth of xenografts in vivo, respectively. Microarray analysis was used to analyze gene expression profile in GCAFs/NFs and VM (+)/VM (−) in vitro. QRT-PCR, western blotting, IHC and CIF were used to detected NOX4 expression in GCAFs/NFs, 3-D culture/co-culture matrices in vitro, the xenografts in vivo and human gallbladder tissue/stroma samples. The correlation between NOX4 expression and clinicopathological and prognostic factors of GBC patients was analyzed. And, the underlying molecular mechanism of GCAFs promoting VM formation and tumor growth in GBC was explored. Results GCAFs promote VM formation and tumor growth in GBC; and the finding was confirmed by facts that GCAFs induced proliferation, invasion, migration and tube formation of GBC cells in vitro, and promoted VM formation and tumor growth of xenografts in vivo. NOX4 is highly expressed in GBC and its stroma, which is the key gene for VM formation, and is correlated with tumor aggression and survival of GBC patients. The GBC patients with high NOX4 expression in tumor cells and stroma have a poor prognosis. The underlying molecular mechanism may be related to the upregulation of NOX4 expression through paracrine IL-6 mediated IL-6/JAK/STAT3 signaling pathway. Conclusions GCAFs promote VM formation and tumor growth in GBC via upregulating NOX4 expression through the activation of IL-6-JAK-STAT3 signal pathway. NOX4, as a VM-related gene in GBC, is overexpressed in GBC cells and GCAFs, which is related to aggression and unfavorable prognosis of GBC patients.

Background Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC). Methods We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed. Results PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05). Conclusions The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.

Background/Aims There have been no nationwide studies to investigate the trends in incidence and 5-year survival rates of intra- and extrahepatic bile duct cancers and gall-bladder cancer. Therefore, our study aimed to describe the incidence and 5-year survival rates of biliary tract cancers by subsites in South Korea. Methods : A total of 86,134 patients with biliary tract cancers were selected from the National Health Information Database. Age-standardized incidence rates and annual percentage changes were calculated. Life-table methods and log-rank tests were used to determine the differences in survival rates. Cox-proportional hazard models were used to estimate the hazard ratio of the patients with biliary tract cancers. Results : The incidence rate of intra-hepatic bile duct cancer decreased by 1.3% annually from 8.8 per 100,000 in 2006 to 7.8 per 100,000 in 2015. Extrahepatic bile duct cancer also showed a decreasing trend by 2.2% per year from 8.7 per 100,000 in 2006 to 6.7 per 100,000 in 2015. Gallbladder cancer showed the greatest decline, with an annual percentage change of 2.8% from 6.3 per 100,000 to 5.2 per 100,000 during the same period. The 5-year survival rates were 30.0% in gallbladder cancer, 27.8% in extrahepatic bile duct cancer, and 15.9% in intra-hepatic bile duct cancer. Conclusion : s The overall incidence rates of intrahepatic and extrahepatic bile duct cancer and gallbladder cancer decreased from 2006 to 2015. Among biliary tract cancers, intrahepatic bile duct cancers exhibited the highest incidence rate and the worst survival rate.

Biliary sludge (or very thick bile) is mainly comprised of calcium bilirubinate granules and lesser amounts of cholesterol crystals, and it can produce a layer of low amplitude of echoes in the most dependent part of the gallbladder (GB). In tumefactive biliary sludge, low-amplitude echoes do not form a fluid–fluid level but instead tend to give the appearance of a polypoid mass that is bounded by a smooth margin, round, and lobulated. Differential diagnoses for an echogenic mass in the GB lumen include GB carcinoma, tumefactive sludge, and gangrenous cholecystitis. In this case report, we describe a rare case in which biliary sludge did not form a fluid–fluid level but tended to accumulate and appear as a polypoid mass within the lumen of the GB. The lesion was finally identified as being tumefactive sludge mimicking neoplasm of the GB.

Gemcitabine (GEM), as an anti-metabolic nucleoside analog, has been shown to have anticancer effects in various tumors, but its chemotherapy resistance is still an important factor leading to poor prognosis of cancer patient. A large number of studies in recent years have shown that autophagy plays an important role in the chemotherapy sensitivity of many tumors, including pancreatic, non-small cell lung, and bladder cancer. However, whether GEM causes autophagy in gallbladder cancer (GBC) and whether it is related to chemotherapy resistance is unknown. In the present study, we demonstrated that GEM induced apoptosis and protective autophagy in GBC cells, which may be related to the AKT/mTOR signaling pathway, and GEM in combination with autophagy inhibitor chloroquine can strengthen the cytotoxic effect of GEM on GBC in vitro and in vivo. These findings showed that both autophagy and AKT/mTOR signals were engaged in GBC cell death evoked by GEM, GBC patients might benefit from this new treatment strategy, and molecular targeted treatment in combination with autophagy inhibitors shows promise as a treatment improvement. [ABSTRACT FROM AUTHOR]

Background: Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens.Methods: Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer-associated genes. Fisher exact and Kruskal-Wallis tests assessed differences in clinicopathologic and genetic factors. Kaplan-Meier methods evaluated differences in overall survival from the time of surgery between mutations.Results: A total of 81 patients were included. Japanese patients (11 patients) were older (median age, 72 years [range, 54-81 years]) compared with patients from Chile (21 patients; median age, 59 years [range, 32-73 years]) and the United States (49 patients; median age, 66 years [range, 46-87 years]) (P = .002) and had more well-differentiated tumors (46% vs 0% for Chile/United States; P < .001) and fewer gallstone-associated cancers (36% vs 67% for Chile and 69% for the United States; P = .13). Japanese patients had a median mutation burden of 6 (range, 1-23) compared with Chile (median mutation burden, 7 [range, 3-20]) and the United States (median mutation burden, 4 [range, 0-27]) (P = .006). Tumors from Japanese patients lacked AT-rich interaction domain 1A (ARID1A) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations, whereas Chilean tumors lacked Erb-B2 receptor tyrosine kinase 3 (ERBB3) and AT-rich interaction domain 2 (ARID2) mutations. SMAD family member 4 (SMAD4) was found to be mutated similarly across centers (38% in Chile, 36% in Japan, and 27% in the United States; P = .68) and was univariately associated with worse overall survival (median, 10 months vs 25 months; P = .039). At least one potentially actionable gene was found to be altered in 80% of tumors.Conclusions: Differences in clinicopathologic variables suggest the possibility of distinct GBCA pathogenesis in Japanese patients, which may be supported by differences in mutation pattern. Among all centers, SMAD4 mutations were detected in approximately one-third of patients and may represent a converging factor associated with worse survival. The majority of patients carried mutations in actionable gene targets, which may inform the design of future trials. [ABSTRACT FROM AUTHOR]

Resumen INTRODUCCIÓN El cáncer de vesícula biliar es una neoplasia poco común, y su frecuencia es variable en las regiones de Perú. OBJETIVO Determinar la frecuencia y describir las características clínicas del cáncer de vesícula biliar en un hospital de referencia al sur de Perú. MÉTODOS Estudiamos los informes de todas las muestras de colecistectomías realizadas entre los años 2009 y 2014, en el servicio de anatomía patológica del Hospital Regional Honorio Delgado. Además, revisamos las historias clínicas de los pacientes que tuvieran algún resultado compatible con cáncer de vesícula biliar. RESULTADOS De 2991 colecistectomías, 75 (2,5%) tuvieron cáncer de vesícula biliar. El síntoma más frecuente en ambos grupos fue el dolor (96,7%), seguido de náusea (87,5%) y vómitos (65,0%). La mayoría de pacientes fueron mujeres (83,3%) mayores de 60 años (65,0%). El tipo histológico más frecuente fue el adenocarcinoma (80,0%). CONCLUSIÓN La frecuencia de cáncer de vesícula biliar en un hospital de referencia del sur de Perú, es de 2,5% mayor a la reportada en otros estudios en las regiones centro y norte del país.

Competing Interests: Conflict of interest: None

Abstract: Background: The optimal surgical extent for T1 gallbladder cancer (GBC) remains controversial. Simple cholecystectomy is routinely performed for T1 GBC while several guidelines recommend extended cholecystectomy for T1b GBC. However, evidence regarding the optimal surgical extent for T1 GBC is lacking. This study aims to systematically evaluate the optimal surgical extent for early GBC with regard to long‐term survival. Methods: A comprehensive literature search in MEDLINE was performed to identify studies with histologically proven GBC and survival data. A total of 22 articles with a total of 2,578 patients were included in the final analysis. Dichotomous data regarding cancer‐related death in all T1, T1a, and T1b GBC cases were extracted. Risk ratios, risk differences, and 95% confidence intervals (CIs) were pooled. Results: The risk ratio between simple and extended cholecystectomy in T1 GBC patients was 1.06 (95% CI 0.97–1.16); T1a, 0.82 (95% CI 0.70–0.96); and T1b, 1.06 (95% CI 0.93–1.22). No significant difference was found according to the extent of surgery in all T1 or T1b GBC cases (P = 0.17 and P = 0.36, respectively). Simple cholecystectomy had significantly lower cancer‐related death in T1a GBC patients (P = 0.01). Conclusion: Simple and extended cholecystectomy showed comparable survival outcomes in T1 GBC patients. [ABSTRACT FROM AUTHOR]

Background: We examined whether the incidental cystic duct nodal status predicts the status of the hepatoduodenal ligament (D1) or common hepatic artery, the pancreaticoduodenal and paraaortic lymph nodes (D2), and the overall prognosis and thus indicates whether an oncologic extended resection (OER) is required.Methods: The study included patients who underwent OER for incidental gallbladder cancer (IGBC) during 1999-2015. Associations between a positive cystic duct node and D2 nodal status and disease-specific survival (DSS) were analyzed.Results: One-hundred-eight-seven patients were included. Seventy-three patients (39%) had the incidental cystic duct node retrieved. Cystic duct node positivity was associated with positive D1 (odds ratio 5.2, p = 0.012) but not with D2. Among all patients, a positive cystic duct node was associated with worse DSS (hazard ratio [HR] 2.09). Patients without residual cancer at OER and positive incidental cystic duct node had similar DSS to patients with negative nodes 70 vs 60% (p = 0.337). Positive D1 (HR 6.07) or positive D2 (HR 13.8) was predictive of worse DSS.Conclusions: Patients with no residual cancer at OER and regional disease limited to their incidental cystic duct node have similar DSS to pN0 patients. The status of the cystic duct node only predicts the status of hepatic pedicle nodes. [ABSTRACT FROM AUTHOR]

Background: Human gallbladder cancer (GBC) is an aggressive malignant neoplasm with a poor prognosis. The development of ideal tools for example tumor cell lines for investigating biological behavior, metastatic mechanism and potential treatment in GBCs is essential. In present study, we established and characterized a GBC cell line derived from primary tumor. Methods: Primary culture method was used to establish this cell line from a primary GBC. Light and electron microscopes, flow cytometry, chromosome analysis, heterotransplantation and immunohistochemistry were used to characterize the epidemic tumor characteristics and phenotypes of this cell line. Results: A novel GBC cell line, named TJ-GBC2, was successfully established from primary GBC. This cell line had characteristic epithelial tumor morphology and phenotypes in consistent with primary GBC, such as polygon and irregular cell shape, increased CA19-9 and AFP levels, and positive expression of CK7, CK8, CK19 and E-cadherin with negative vimentin. Moreover, about 25% of the cells were in the S-G2/M phase; abnormity in structure and number of chromosome with a peak number of 90-105 and 80% hypertetraploid were observed. Furthermore, this cell line had higher invasion and highest migration abilities compared to other GBC cell lines; and metastatic-related marker MMP9 and nm23 were positively expressed. Conclusions: A novel highly aggressive GBC cell line TJ-GBC2 was successfully established from primary GBC. TJ-GBC2 cell line may be efficient tool for further investigating the biological behaviors, metastatic mechanism and potential targeted therapy of human GBC. [ABSTRACT FROM AUTHOR]