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Background: Gallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients. Methods: Patients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit. Results: Eight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75% for 1-, 3-, and 5-year survival. The calibration curves, Kaplan-Meier curves and decision curves also indicated good prognostic performance and clinical benefit, surpassing traditional indicators TNM staging and CA199 levels. The reliability of results was further proved in the independent external testing set. Conclusions: The novel nomogram exhibited good prognostic efficacy and robust generalizability in GBC patients, which might be a promising tool for aiding clinical decision-making. Highlights: • A representative surgical cohort of GBC was retrospectively established. • Clinical variables related to surgical management were comprehensively collected and analyzed. • The study introduced the independent prognostic significance of aCCI and CA125 in GBC. • A novel multi-factor nomogram was developed with satisfactory prognostic performance, as confirmed by internal and external validations. [ABSTRACT FROM AUTHOR]

Abstract Background Cross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases. Methods Transcriptomic data obtained from patients with gallbladder cancer (GBC) was assessed for the differential expression of antisense RNAs (asRNAs). The Basic Local Alignment Search Tool (BLAST) was used for cross-species analysis with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better. Results A total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue compared to that of normal gallbladder. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these 15 asRNAs, (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including (Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and, Klebsiella pneumoniae sp.), indicating potential HGT during evolution. Conclusion The results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development.

Objective: This study aimed to evaluate the clinical efficacy and safety of anlotinib as maintenance therapy in patients with advanced cholangiocarcinoma following first-line chemotherapy. Methods: This retrospective study enrolled 154 patients with advanced biliary tract cancer admitted to the hospital between January 2020 and December 2022. All patients received first-line intravenous chemotherapy with gemcitabine combined with cisplatin, oxaliplatin, or tegafur. Among the 106 patients who achieved disease control, 47 received oral anlotinib hydrochloride (12 mg daily, 2 weeks on/1 week off) as maintenance therapy. Clinical efficacy, including ORR, DCR, DOR, PFS, and OS, was compared between the anlotinib maintenance and non-maintenance groups. Subgroup analysis based on NLR levels was also performed. Results: Among the 47 anlotinib maintenance patients, the ORR was 21.28% and the DCR was 51.06%. The median DOR was 36 weeks, and the median PFS was 43 weeks in the anlotinib group, versus 28 weeks and 38 weeks in the non-maintenance group, respectively. The median OS was not reached in the anlotinib group but was 48 weeks in the non-maintenance group. Patients receiving anlotinib maintenance had significantly longer DOR, PFS, and OS (all p < 0.05). Patients with low NLR levels had better survival benefits from anlotinib. Conclusion: Maintenance therapy with anlotinib demonstrates potential efficacy and a reliable safety profile in patients with advanced cholangiocarcinoma following first-line treatment. The efficacy of anlotinib therapy appears to be influenced by NLR levels. Further validation with larger sample sizes is warranted to strengthen the robustness and reliability of the results. [ABSTRACT FROM AUTHOR]

Background: Cross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases. Methods: Transcriptomic data obtained from patients with gallbladder cancer (GBC) was assessed for the differential expression of antisense RNAs (asRNAs). The Basic Local Alignment Search Tool (BLAST) was used for cross-species analysis with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better. Results: A total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue compared to that of normal gallbladder. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these 15 asRNAs, (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including (Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and, Klebsiella pneumoniae sp.), indicating potential HGT during evolution. Conclusion: The results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). Methods: Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. Results: Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89–30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61–7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67–43.33 months) for Group 3 (n = 4), and 19 months (range 7.89–30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). Conclusion: Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging. [ABSTRACT FROM AUTHOR]

Background: Biliary intraepithelial neoplasia (BilIN), a noninvasive precursor of cholangiocarcinoma, can manifest malignant transformation. Since cholangiocarcinoma (CCA) may progress due to chronic inflammation in the bile ducts and gallbladder, choledochal cysts are considered a precursor to CCA. However, BilIN has rarely been reported in children, to date. Methods: We reviewed medical records of patients (< 18 years of age, n = 329) who underwent choledochal cyst excision at Asan Medical Center from 2008 to 2022. BilIN was diagnosed in 15 patients. Subsequent analyses were performed of the demographics, surgical procedures, clinical course, and outcomes in these patients. Subgroup analysis and multivariate logistic regression test were performed to identify factors influencing BilIN occurrence. Results: The mean age of the patients included in our study was 40.1 ± 47.6 months. In 15 patients, BilIN of various grades was diagnosed. Todani type I was prevalent in 80% of the patients. The median age at surgery was 17 months. During a mean follow-up of 63.3 ± 94.0 months, no adverse events such as stone formation in the remnant intrapancreatic common bile duct and intrahepatic duct or cholangiocarcinoma were observed, indicating a favorable outcome until now. Conclusions: The potential progression of choledochal cysts to BilIN in children was demonstrated. These results could underscore the importance of early and comprehensive excision of choledochal cysts, including resection margins for associated lesions and more thorough postoperative surveillance in patients with or at risk of BilIN. [ABSTRACT FROM AUTHOR]

Background: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia–dysplasia–carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. Case presentation: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia–dysplasia–carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. Conclusions: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia–dysplasia–carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca. [ABSTRACT FROM AUTHOR]

Abstract Purpose The Naples prognostic score (NPS) is a comprehensive prognostic model that includes inflammatory and nutrition-related indicators and is increasingly used as a prognostic score for various malignant tumors. Given its predictive effect on prognosis in patients with gallbladder cancer, it is currently unclear. This study aimed to investigate the role of preoperative NPS in predicting prognosis in gallbladder cancer surgery patients. Patients and methods A retrospective analysis was performed for 135 patients who underwent radical surgery for gallbladder cancer without preoperative treatment between March 2011 and January 2020. NPS was calculated by measuring the preoperative total cholesterol value, serum albumin value, neutrophil–lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). They were then divided into 3 groups (groups 0, 1, and 2) based on NPS scores. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Plot time-dependent receiver operating characteristic (ROC) curves to compare the prognostic value of scoring systems. Finally, a nomogram model was developed with independent prognostic factors. Results Multivariate analysis showed that NPS was an independent risk factor affecting OS (HR = 3.417, p

Abstract Background For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3–15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA. Methods Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009–May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan–Meier method. Results Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15–25 months) for patients with pCCA and 17 months (95% CI 11–23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3–17 months) compared 17 months (95% CI 15–19 months) for patients with pCCA (p = 0.010). Conclusions At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies.

Purpose: The Naples prognostic score (NPS) is a comprehensive prognostic model that includes inflammatory and nutrition-related indicators and is increasingly used as a prognostic score for various malignant tumors. Given its predictive effect on prognosis in patients with gallbladder cancer, it is currently unclear. This study aimed to investigate the role of preoperative NPS in predicting prognosis in gallbladder cancer surgery patients. Patients and methods: A retrospective analysis was performed for 135 patients who underwent radical surgery for gallbladder cancer without preoperative treatment between March 2011 and January 2020. NPS was calculated by measuring the preoperative total cholesterol value, serum albumin value, neutrophil–lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). They were then divided into 3 groups (groups 0, 1, and 2) based on NPS scores. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Plot time-dependent receiver operating characteristic (ROC) curves to compare the prognostic value of scoring systems. Finally, a nomogram model was developed with independent prognostic factors. Results: Multivariate analysis showed that NPS was an independent risk factor affecting OS (HR = 3.417, p < 0.05). The time-dependent ROC curve results showed that NPS had a better predictive value on survival prognosis than other indicators. The nomogram constructed according to independent factors such as NPS has a good predictive ability for OS. Conclusion: As a simple and reliable tool, the NPS has important predictive value in the survival prognosis of gallbladder cancer patients. The nomogram model constructed by NPS will help determine prognosis and make individualized treatment decisions. [ABSTRACT FROM AUTHOR]

Background: For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3–15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA. Methods: Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009–May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan–Meier method. Results: Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15–25 months) for patients with pCCA and 17 months (95% CI 11–23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3–17 months) compared 17 months (95% CI 15–19 months) for patients with pCCA (p = 0.010). Conclusions: At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Cholecystitis can represent a comorbidity during gallbladder cancer surgery; nonetheless, the prognostic impact of acute cholecystitis comorbidity remains unclear. This study aimed to evaluate the impact of acute cholecystitis comorbidity on prognosis after gallbladder cancer surgery, with adjustment for background factors using propensity score analysis. Methods A total of 218 patients who underwent gallbladder cancer surgery at our institute between 1986 and 2022 were retrospectively included in the analysis. Patients were divided into two groups according to the presence or absence of acute cholecystitis at the time of surgery. Background factors were adjusted by including intraoperative bile leakage as a covariate in propensity score calculation. Overall survival and recurrence-free survival were compared between the two groups using one-to-one propensity score matching and inverse probability weighting. Results Of the 218 patients, 37 had coexisting acute cholecystitis. In one-to-one propensity score matching, the overall survival time in the acute cholecystitis group tended to be shorter than that in the non-acute cholecystitis group, although not significantly (hazard ratio, 2.41; 95% confidence interval, 0.96–6.06). Other analyses using inverse probability weighting showed significantly poor overall survival in the acute cholecystitis group. Regarding recurrence-free survival in propensity score matching, the acute cholecystitis group showed a significantly shorter duration than the non-acute cholecystitis group (hazard ratio, 6.69; 95% confidence interval, 1.46–30.6). The inverse probability weighting-adjusted analysis also indicated a significantly higher risk of recurrence in the acute cholecystitis group. Conclusions Acute cholecystitis comorbidity at the time of gallbladder cancer surgery may have a negative impact on gallbladder cancer prognosis.

Background: Cholecystitis can represent a comorbidity during gallbladder cancer surgery; nonetheless, the prognostic impact of acute cholecystitis comorbidity remains unclear. This study aimed to evaluate the impact of acute cholecystitis comorbidity on prognosis after gallbladder cancer surgery, with adjustment for background factors using propensity score analysis. Methods: A total of 218 patients who underwent gallbladder cancer surgery at our institute between 1986 and 2022 were retrospectively included in the analysis. Patients were divided into two groups according to the presence or absence of acute cholecystitis at the time of surgery. Background factors were adjusted by including intraoperative bile leakage as a covariate in propensity score calculation. Overall survival and recurrence-free survival were compared between the two groups using one-to-one propensity score matching and inverse probability weighting. Results: Of the 218 patients, 37 had coexisting acute cholecystitis. In one-to-one propensity score matching, the overall survival time in the acute cholecystitis group tended to be shorter than that in the non-acute cholecystitis group, although not significantly (hazard ratio, 2.41; 95% confidence interval, 0.96–6.06). Other analyses using inverse probability weighting showed significantly poor overall survival in the acute cholecystitis group. Regarding recurrence-free survival in propensity score matching, the acute cholecystitis group showed a significantly shorter duration than the non-acute cholecystitis group (hazard ratio, 6.69; 95% confidence interval, 1.46–30.6). The inverse probability weighting-adjusted analysis also indicated a significantly higher risk of recurrence in the acute cholecystitis group. Conclusions: Acute cholecystitis comorbidity at the time of gallbladder cancer surgery may have a negative impact on gallbladder cancer prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Fluorescent imaging may aid with the precise diagnosis and treatment of patients with gallbladder cancer. In this study, we sought to demonstrate whether the da Vinci® surgical system and Firefly™ camera could detect EGFR-targeted fluorescent images in orthotopic mouse models of gallbladder cancer. Methods An orthotopic mouse model of gallbladder cancer was created by injecting NOZ gallbladder cancer cells mixed with Matrigel into the gallbladder. In vivo imaging of subcutaneous and orthotopic gallbladder tumors was performed after the injection of DyLight 650- or 800-conjugated EGFR antibody. Results Western blotting, flow cytometry, and confocal microscopy showed the presence of EGFR in NOZ cells, but not in HEK293 cells. Subcutaneous NOZ cell tumors fluoresced after injection with fluorescent EGFR antibody, but subcutaneous HEK293 tumors did not. Fluorescent EGFR antibody made orthotopic NOZ tumors fluoresce, with an intensity stronger than that in the surrounding normal tissues. Histochemical examination confirmed the location of the tumors inside the gallbladder and adjacent liver parenchyma. Fluorescent signal was also detected in orthotopic gallbladder tumors with Firefly™ camera. Conclusion Our study showed that fluorescent EGFR antibodies and the Firefly camera in the da Vinci system can detect fluorescing gallbladder tumors, which demonstrates their potential use for molecular imaging-based prevision surgery in the near future.

Abstract Background Hepatopancreaticoduodenectomy (HPD) is one of the most complex procedures, and it is very rarely reported. Laparoscopic HPD (LHPD) is even rarer. To date, there are only 3 reports of LHPD for locally advanced gallbladder cancer (GBC) or extrahepatic cholangiocarcinoma (ECC). This is the first report of LHPD for synchronous GBC and ECC. Case presentation A 75-year-old female patient complained of jaundice for 2 weeks without fever or abdominal pain. She was diagnosed with synchronous GBC and ECC. After a comprehensive preparation, she underwent a laparoscopic pancreaticoduodenectomy and resection of hepatic segments of IVb and V, and her digestive tract reconstruction followed Child’s methods. She was discharged on the 12th day postoperatively without pancreatic leakage, biliary leakage, or liver failure. Conclusions LHPD is safe and feasible for selected cases of GBCs or ECCs.

Background: Disseminated disease (DD) is often found at (re-)exploration in gallbladder cancer (GBC) patients. We aimed to assess the yield of staging laparoscopy (SL) and identify predictors for DD. Methods: This retrospective study included patients from all Dutch academic centres with primary GBC (pGBC) and incidentally diagnosed GBC (iGBC) planned for (re-)resection. The yield of SL was determined. In iGBC, predictive factors for DD were assessed. Results: In total, 290 patients were included. Of 183 included pGBC patients, 143 underwent laparotomy without SL, and 42 (29%) showed DD perioperatively. SL, conducted in 40 patients, identified DD in eight. DD was found in nine of 32 patients who underwent laparotomy after SL. Of 107 included iGBC patients, 100 underwent laparotomy without SL, and 19 showed DD perioperatively. SL, conducted in seven patients, identified DD in one. Cholecystitis (OR = 4.25; 95% CI 1.51–11.91) and primary R1/R2 resection (OR = 3.94; 95% CI 1.39–11.19) were independent predictive factors for DD. Conclusions: In pGBC patients, SL may identify DD in up to 20% of patients and should be part of standard management. In iGBC patients, SL is indicated after primary resection for cholecystitis and after initial R1/R2 resection due to the association of these factors with DD. [ABSTRACT FROM AUTHOR]

Background: The present study aims to evaluate the survival status of patients with gallbladder cancer (GBC) and explore the prognostic factors for the improvement and preventions. Methods: The study consists of 176 patients with clinically diagnosed gallbladder cancer; the study was conducted between 2019 and 2021 registered at Kamala Nehru Memorial Cancer Hospital, Prayagraj, India. The survival rates were analyzed by the Kaplan-Meier method; survival rate difference was analyzed by log-rank test, prognosis factors; and hazard ratio for mortality outcomes was estimated using Cox regression method. Results: The overall median survival time of patients was 5 months with the 1-year, 2-year, and 3-year survival rates of 24.4%, 8.5%, and 4.5%, respectively. The 3-year survival for patients with jaundice was 2.9%, liver infiltration (4.2%), gallstones (0.8%), and with advanced tumor grade (1.4%). Elderly GBC patients had lower survival rates (3.8%), while the 3-year overall survival for patients residing in urban areas dropped to zero. No patients in the tumor stage (T3/T4) and with distance metastasis stage survived in 3 years, while only 1.1% of patients with advanced nodal stage survived. On receiving surgery and radiation therapy, the 3-year survival rate increased to 19.5% and 35%, respectively. The results of multivariate analysis showed that urban region (HR = 1.568, p = 0.040), gallstone or not (1.571, p = 0.049), N stage (HR = 1.468, p = 0.029), and M stage (HR = 2.289, p < 0.0001) were independent risk factors for prognosis, while surgery or not (HR = 0.573, p = 0.030) was the protective factor for the prognosis of GBC. Conclusion: The overall survival of GBC in the Gangetic belt is poor. The geographical region of patients, gallstones, and N and M stage was the risk factors for prognosis, while surgery or not was the protective factor for the prognosis of GBC. [ABSTRACT FROM AUTHOR]

Background: SMAD4 is a key mediator of TGFβ signaling and one of the mutated genes in extrahepatic bile duct cancer (eBDC). It has been also reported that SMAD4 has dual functions, in carcinogenesis via silencing and in tumor invasion/metastasis via signaling, depending on tumor stage. We previously visualized more nuclear transitioning functional SMAD4 at the tumor invasion front than the central lesion. So, we investigated the localization of functional SMAD4 (e.g., invasion area or metastasis lesion) and its association with chemotherapy and chemo-radiation therapy. Methods: We performed SMAD4 immunostaining on 98 resected eBDC specimens and evaluated the presence of the functional form of nuclear SMAD4 at the central lesion, invasion front, and metastatic lymph node. We also examined the influence on chemotherapy after recurrence (n = 33) and neoadjuvant chemo-radiation therapy (NAC-RT, n = 21) and the prognostic value of using retrospective data. Results: In 73 patients without NAC-RT, 8.2% had loss of SMAD4 expression and 23.3% had heterogeneous expression. Patients without SMAD4 expression at any site had significantly poorer overall survival (OS) than other patients (P = 0.014). Expression of SMAD4 at the invasion front was related to better survival (recurrence-free survival [RFS] P = 0.033; OS P = 0.047), and no SMAD4 expression at the metastatic lymph node was related to poorer OS (P = 0.011). The patients who had high SMAD4 expression had poorer prognosis after recurrence (RFS P = 0.011; OS P = 0.056). At the residual cancer in the resected specimen, SMAD4 was highly expressed after NAC-RT (P = 0.039). Conclusions: Loss of SMAD4 protein expression was a poor prognostic factor in eBDC at resectable stage. However, the intensity of functional SMAD4 in eBDC is a marker of resistance to chemo-radiotherapy and malignant potential at advanced stages. [ABSTRACT FROM AUTHOR]

Background: Fluorescent imaging may aid with the precise diagnosis and treatment of patients with gallbladder cancer. In this study, we sought to demonstrate whether the da Vinci® surgical system and Firefly™ camera could detect EGFR-targeted fluorescent images in orthotopic mouse models of gallbladder cancer. Methods: An orthotopic mouse model of gallbladder cancer was created by injecting NOZ gallbladder cancer cells mixed with Matrigel into the gallbladder. In vivo imaging of subcutaneous and orthotopic gallbladder tumors was performed after the injection of DyLight 650- or 800-conjugated EGFR antibody. Results: Western blotting, flow cytometry, and confocal microscopy showed the presence of EGFR in NOZ cells, but not in HEK293 cells. Subcutaneous NOZ cell tumors fluoresced after injection with fluorescent EGFR antibody, but subcutaneous HEK293 tumors did not. Fluorescent EGFR antibody made orthotopic NOZ tumors fluoresce, with an intensity stronger than that in the surrounding normal tissues. Histochemical examination confirmed the location of the tumors inside the gallbladder and adjacent liver parenchyma. Fluorescent signal was also detected in orthotopic gallbladder tumors with Firefly™ camera. Conclusion: Our study showed that fluorescent EGFR antibodies and the Firefly camera in the da Vinci system can detect fluorescing gallbladder tumors, which demonstrates their potential use for molecular imaging-based prevision surgery in the near future. [ABSTRACT FROM AUTHOR]

Background: Hepatopancreaticoduodenectomy (HPD) is one of the most complex procedures, and it is very rarely reported. Laparoscopic HPD (LHPD) is even rarer. To date, there are only 3 reports of LHPD for locally advanced gallbladder cancer (GBC) or extrahepatic cholangiocarcinoma (ECC). This is the first report of LHPD for synchronous GBC and ECC. Case presentation: A 75-year-old female patient complained of jaundice for 2 weeks without fever or abdominal pain. She was diagnosed with synchronous GBC and ECC. After a comprehensive preparation, she underwent a laparoscopic pancreaticoduodenectomy and resection of hepatic segments of IVb and V, and her digestive tract reconstruction followed Child's methods. She was discharged on the 12th day postoperatively without pancreatic leakage, biliary leakage, or liver failure. Conclusions: LHPD is safe and feasible for selected cases of GBCs or ECCs. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreaticobiliary maljunction (PBM) is a congenital abnormality in which the pancreatic and biliary ducts join anatomically outside the duodenal wall resulting in the regurgitation of pancreatic juice into the biliary tract (pancreatobiliary reflux). Persistent pancreatobiliary reflux causes injury to the epithelium of the biliary tract and promotes the risk of biliary cancer. Intracholecyctic papillary neoplasm (ICPN) has been highlighted in the context of a cholecystic counterpart of intraductal papillary mucinous neoplasm of the pancreas and the bile duct, but the tumorigenesis of ICPNs remains unclear. Case presentation A 52-year-old Japanese woman was referred for the assessment of dilation of the bile duct. Computed tomography which revealed an enhanced mass in the gallbladder and endoscopic retrograde cholangiopancreatography confirmed that the confluence of the main pancreatic duct and extrahepatic bile duct (EHBD) was located outside the duodenal wall. Under the diagnosis of gallbladder cancer with PBM, cholecystectomy with full thickness dissection, EHBD resection, lymph node dissection, and hepaticojejunostomy were performed. Macroscopic examination of the resected specimen showed that the cystic duct was dilated and joined into the EHBD just above its confluence with the pancreatic duct, and the inflamed change of non-tumorous mucosa of gallbladder indicating that there was considerable mucosal injury due to pancreatobiliary reflux to the gallbladder. Histopathological examination revealed that the gallbladder tumor was a gastric-type ICPN with non-invasive component. Either KRAS gene mutation or p53 protein expression that were known to be associated with the carcinogenesis of biliary cancer under the condition of pancreatobiliary reflux was not detected in the tumor cells of ICPN. Conclusion The present case might suggest that there was no association between PBM and ICPN. To reveal the tumorigenesis of ICPN and its attribution to pancreatobiliary reflux, however, further study is warranted.

Abstract Background Gallbladder cancer (GBC) is the most common and aggressive extra hepatic biliary tree cancer (BTC) with dismal outcome. Complete surgical resection is the treatment of choice. Chemotherapy is used for palliation in advanced GBC where surgery is not possible, and the most commonly used agent is gemcitabine in combination with cisplatin or oxaliplatin or with capecitabine regimens. Complete remissions are hardly encountered in these cases; therefore, it is important to combine standard therapies with molecular targeting. Case presentation A 60-year-old woman presented with pain in abdomen and loss of appetite for 1 month, and imaging showed locally advanced gallbladder carcinoma with liver metastasis. After biopsy confirmation, patient was initially started on gemcitabine and oxaliplatin combination followed by gene sequencing, which showed Tp53 (exon 7—c.713 G > A and exon 5—c.376-2A > G) and EGFR (exon 20—T790M) mutation, and erlotinib was added to chemotherapy, after 6 cycles of chemotherapy patient showed a 90% partial radiological response as per RECIST criteria. Conclusion This case reports the possible efficacy of erlotinib in combination with gemcitabine and oxaliplatin in treating an EGFR-mutated GBC with liver metastasis. To our knowledge, this is the first article reporting the response to erlotinib combination therapy with this particular solitary mutation.

Abstract Objective The aim of the study is to evaluate the impact of application of surgical strategies at different cancer stages on the survival of gallbladder cancer (GBC) patients. Methods The patients with GBC were divided into 3 groups according to their received surgical strategies: simple resection (full-thickness cholecystectomy for removal of primary tumor site), radical resection (gallbladder bed removal combined with partial hepatectomy), and palliative surgery (treatment at advanced stages). The overall survival (OS) of GBC patients who were received different surgical strategies was compared. Results Survival analysis showed that radical resection had a best OS at clinical stage II, and simple resection had a best OS at tumor clinical stage IV. Cox hazard proportional regression analysis showed that more advanced tumor stages, tumor location of gallbladder body or neck, and CA199 ≥ 27 U/mL were the major risk factors for the OS of GBC. Conclusions At tumor stage II, radical resection should be the most effective surgical therapy for GBC. However, the effect of radical resection at advanced stages could be restricted. The utilization of radical resection should be increased at tumor stage II for a better long-term survival outcome.

Background: The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. Methods: The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. Results: Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. Conclusion: LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1. [ABSTRACT FROM AUTHOR]

Abstract Background The indications for extrahepatic bile duct (EHBD) resection remain a major controversy in the surgical management of patients with gallbladder cancer. On the other hand, perineural invasion (PNI) was reported as an important factor in patients with gallbladder cancer because gallbladder cancer cells frequently spread to the tissues surrounding the EHBD via perineural routes. We assessed the correlation of PNI with clinicopathological factors in patients with gallbladder cancer to elucidate EHBD resection indications specifically in patients with PNI. Methods This retrospective study assessed the PNI status of 50 patients with gallbladder cancer who underwent curative resection and examined the correlation between the presence of PNI and clinicopathological factors. Results Thirteen patients (26%) were PNI positive. PNI was significantly correlated with male sex, proximal-type tumor, lymphatic and vascular invasion, and advanced T stage. Multivariate analysis found that PNI positivity (p < 0.001), lymphatic invasion (p = 0.007), and nodal stage (p < 0.001) were independent prognostic factors. PNI was never observed in patients with stage T1 cancer. Conversely, PNI was detected rarely in distal-type tumors, all of whom developed various types of recurrences. Conclusions These results clearly demonstrated the prognostic impact of PNI in patients with gallbladder cancer. We suggest that EHBD resection in combination with cholecystectomy may not be useful for distal-type tumors from a perspective of PNI.

Abstract Background The pure large cell type is a rare variant of primary neuroendocrine carcinoma of the gallbladder. Few reports have mentioned extended survival. Although a multimodal treatment has been described in the treatment of such rare disease, redo liver resection has not yet been mentioned. Case report A 67-year-old lady was found to have poorly differentiated, high grade, pure large cell neuroendocrine tumor of the gallbladder after cholecystectomy for gallstones. After the diagnosis, staging workup showed a lesion in segment IVB/V of the liver, and chromogranin was elevated (982 mcg/L). The patient underwent central inferior hepatectomy and wedge excision of a lesion in segment III (discovered intra-operatively), with hilar lymphadenectomy. Three months after the first liver resection, she developed a new liver lesion II/III and underwent left lateral liver resection. The patient remained disease-free for 4 months following the second liver resection but then developed recurrent liver disease and was started on chemotherapy. Further progression led to multi-organ failure and death at 26 months from initial diagnosis. Conclusion This is the first reported repeat liver resection in such a rare disease that has led to extended overall survival. We suggest that a group of selected patients with this rare malignancy, and liver-limited disease, may benefit from repeated liver resection.

Abstract Background Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the gallbladder are extremely rare; indeed, the English expert literature reports a mere handful of case reports and case series on this topic. According to the WHO classification of 2010, MINEN are considered to be tumors consisting of two major components, neuroendocrine and non-neuroendocrine, each of which hosts at least 30% of the total cellular population. To date, the etiology and pathogenesis of MINEN have not been precisely determined and the non-specific symptoms generally result in late diagnosis (mainly in the terminal stages of the condition) and contribute to the generally poor prognosis. As far as the management of the disease is concerned, radical surgery plays a crucial role; however, the significance of surgical debulking and biological therapy applying somatostatin analogues has not yet been determined. Case presentation A 56-year-old female was referred to our department for a rapidly progressing tumor in the subhepatic area along with the infiltration of S5 and S6 liver segments. With regard to preoperative findings, the tumor appeared as operable, although, during the surgery, an extensive involvement of the hepatoduodenal ligament by the tumor through the lymph nodes was revealed. Due to acute perioperative bleeding from the necrotic tumor, we decided to perform modified resection. Histologically, the tumor was confirmed as MINEN of gallbladder, where the neuroendocrine component was dominant over the non-neuroendocrine component. Six weeks after the discharge, the patient underwent a follow-up CT revealing large recurrence of the disease. Thereafter, the patient was started on systemic therapy with etoposide and carboplatin in combination with somatostatin analogues. Thirteen months after the surgery, the patient is in good clinical condition, and while a recently performed PET/MRI scan revealed a hepatic lesion and hilar lymphadenopathy in full regression, there was a spread of small peritoneal and pleural metastases. The patient remains in the follow-up care. Conclusions The occurrence of mixed neuroendocrine-non-neuroendocrine neoplasms is extremely rare. Radical surgery remains the only potentially effective approach to the cure of this disease. The role of biological therapy and debulking in the management of the disease has not yet been precisely defined. In our experience, both of these methods have the potential to positively influence overall survival rates and the postoperational quality of life of patients.

Background: The associating liver partitioning and portal vein occlusion for staged hepatectomy (ALPPS) procedure is gaining interest because it brings hope to patients who cannot undergo radical surgical resection due to insufficient remnant liver volume. However, the indications and technical aspects of this procedure are still under debate. This report demonstrates the technical aspects of the first two-stage robotic ALPPS for HCC. Case presentation: A 55-year-old man with type II portal vein variation was diagnosed with hepatocellular carcinoma. Preoperative 3D reconstruction of the liver based on CT showed a future liver remnant/standard liver volume (FLR/SLV) of 24.45%. The ALPPS procedure was performed using the da Vinci Si system. At the first stage of the operation, we removed the gallbladder and ligated the right anterior branch of the portal vein and the right posterior branch. Following blocking of the hepatic hilum, the liver parenchyma was removed 1 cm away from the right side of the falciform ligament in an incision manner from the top to the bottom and from shallow to deep. The second-stage operation was performed on the 12th postoperative day with a FLR/SLV of 45.13%. During this step, the right hemiliver plus left medial section was separated and removed. Postoperative pathology showed a negative margin. The operative times were 195 and 217 min, respectively. Estimated blood loss was 250 and 500 ml, respectively. There was no need for transfusion or hospitalization in intensive care. The patient was discharged on the 6th postoperative day. Recovery was uneventful after both stages, and the patient did not present any sign of liver failure. Elevation of liver enzymes was minimal. The patient had no evidence of the disease 14 months after the procedure. Conclusions: The two-stage robotic ALPPS procedure is a safe and feasible technique for select patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Gallbladder neuroendocrine neoplasm is a rare disease that is divided into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Clear cell NETs of the gallbladder are extremely rare. We report the case of a patient with polypoid clear cell NET G1 of the gallbladder who underwent laparoscopic cholecystectomy. Case presentation: A 10-mm pedunculated polyp in the gallbladder neck was detected on a follow-up abdominal ultrasound in a 60-year-old man with chronic hepatitis and hepatitis B without medication. Six months later, an abdominal ultrasound revealed that the tumor had enlarged to 12 mm in size. He was asymptomatic and had no abnormalities in other laboratory examinations, including the tumor markers, carcinoembryonic antigen and CA19-9. Abdominal ultrasound showed a 12-mm polyp in the neck of the gallbladder with perfusion and focal thickening of the gallbladder wall. A gallbladder stone was also seen in the fundus. An enhanced computed tomography scan and magnetic resonance imaging revealed a polypoid lesion and gallbladder stone located at the neck of the gallbladder and the fundus, respectively. Malignancy could not be excluded, and hence, a laparoscopic cholecystectomy was performed. Pathologically, a pedunculated polyp (14 × 11 × 15 mm) was observed in the neck of the gallbladder, and the polypoid lesion comprised nests or trabecular growths of clear NET cells in the lamina propria (ENETS: T1N0M0; AJCC: T1aN0M0). Immunohistochemical staining with synaptophysin, chromogranin A, and CD56 was confined to the tumor. The pathological diagnosis was clear cell NET G1 of the gallbladder. Although clear cell NET is often described as a distinct manifestation of von Hippel-Lindau disease (VHL), the patient had no past medical or family history of VHL. Until his one-and-a-half-year follow-up, the patient was doing well and without any signs of recurrence. Conclusion: We report an extremely rare case of gallbladder clear cell NET G1. When NET G1 is incidentally identified in a gallbladder surgical specimen, clinical information and pathological findings should be considered as references. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer (GBC) is the most common and aggressive extra hepatic biliary tree cancer (BTC) with dismal outcome. Complete surgical resection is the treatment of choice. Chemotherapy is used for palliation in advanced GBC where surgery is not possible, and the most commonly used agent is gemcitabine in combination with cisplatin or oxaliplatin or with capecitabine regimens. Complete remissions are hardly encountered in these cases; therefore, it is important to combine standard therapies with molecular targeting. Case presentation: A 60-year-old woman presented with pain in abdomen and loss of appetite for 1 month, and imaging showed locally advanced gallbladder carcinoma with liver metastasis. After biopsy confirmation, patient was initially started on gemcitabine and oxaliplatin combination followed by gene sequencing, which showed Tp53 (exon 7—c.713 G > A and exon 5—c.376-2A > G) and EGFR (exon 20—T790M) mutation, and erlotinib was added to chemotherapy, after 6 cycles of chemotherapy patient showed a 90% partial radiological response as per RECIST criteria. Conclusion: This case reports the possible efficacy of erlotinib in combination with gemcitabine and oxaliplatin in treating an EGFR-mutated GBC with liver metastasis. To our knowledge, this is the first article reporting the response to erlotinib combination therapy with this particular solitary mutation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to evaluate the impact of application of surgical strategies at different cancer stages on the survival of gallbladder cancer (GBC) patients. Methods: The patients with GBC were divided into 3 groups according to their received surgical strategies: simple resection (full-thickness cholecystectomy for removal of primary tumor site), radical resection (gallbladder bed removal combined with partial hepatectomy), and palliative surgery (treatment at advanced stages). The overall survival (OS) of GBC patients who were received different surgical strategies was compared. Results: Survival analysis showed that radical resection had a best OS at clinical stage II, and simple resection had a best OS at tumor clinical stage IV. Cox hazard proportional regression analysis showed that more advanced tumor stages, tumor location of gallbladder body or neck, and CA199 ≥ 27 U/mL were the major risk factors for the OS of GBC. Conclusions: At tumor stage II, radical resection should be the most effective surgical therapy for GBC. However, the effect of radical resection at advanced stages could be restricted. The utilization of radical resection should be increased at tumor stage II for a better long-term survival outcome. [ABSTRACT FROM AUTHOR]

Backgrounds: The number of appendectomies and cholecystectomies performed is gradually increasing worldwide. An increasing incidence of colorectal cancer (CRC) after appendectomy and cholecystectomy has been reported, but the location of tumors in certain segments of the colon and rectum after appendectomy and cholecystectomy is still uncertain. We aimed to evaluate the distribution of the locations of colorectal cancer after appendectomy and/or cholecystectomy in patients who underwent CRC surgery. Methods: We reviewed the medical records of patients who had undergone CRC surgery between 2015 and 2017 for the presence of previous appendectomy/cholecystectomy. Data were collected from the Colorectal Data Base of the University of Szeged, Department of Surgery. Results: Surgery for CRC was performed in 640 patients during the study period. Data of 604 patients were analyzed. Appendectomy was performed in 100 patients (16.6%), cholecystectomy in 65 (10.8%), and both interventions in 18 (3%) before the CRC surgery. Out of those patients who underwent appendectomy alone, 92 (92%) had undergone appendectomy more than 10 years before the CRC surgery. Also in these 100 patients, the prevalence of right-sided colon cancer (CC) was 35% (n = 35), in comparison with the prevalence among the 504 other patients (20.4%, n = 103). The prevalence of right-sided CC among patients who underwent cholecystectomy alone was 36.9% (n = 24), in comparison with 21.2% (n = 114) of the 539 other patients. Conclusions: A significant left to right side shift in CRC was noted among patients who had previously undergone appendectomy/cholecystectomy. Because right-sided CC has a worse prognosis, the role of incidental appendectomy and routine cholecystectomy seems that need re-evaluation. [ABSTRACT FROM AUTHOR]

Background: Incidental gallbladder carcinoma is often discovered after elective laparoscopic cholecystectomy for cholecystitis or cholecystolithiasis. Port site recurrences may occur. Patients with port site metastases of gallbladder carcinoma have a poor prognosis. Case presentation: A 61-year-old man underwent an elective laparoscopic cholecystectomy because of cholecystitis and gallstones. Pathology revealed a gallbladder carcinoma. After referral to a tertiary center, radical re-resection followed. Three years later, an epigastric port site recurrence emerged, partially fixed to the xiphoid process. A wide abdominal wall resection was performed, including part of the xiphoid process. Follow-up was continued with periodical imaging and standard blood work. Three years after resection of this port site metastasis, the patient presented with an occasionally painful mass in the left axilla. Pathology revealed the presence of an adenocarcinoma, most likely arising from the prior gallbladder carcinoma. Given the extensive dissemination and limited symptoms in the axillary node, we decided against a surgical intervention, instead of adopting a wait-and-see policy. Disease progression occurred within 1 year, and the patient was treated with palliative radiotherapy, followed by palliative chemotherapy. The patient died of metastatic disease approximately 6.5 years after the initial cholecystectomy. Conclusions: Port site recurrences of (incidental) gallbladder carcinoma occur after laparoscopic cholecystectomy, despite preventive perioperative measures. Patients with port site recurrences can develop axillary lymph node metastases, similar to other truncal malignancies. Surgical interventions should be limited. [ABSTRACT FROM AUTHOR]

Background and aim: Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. Material and methods: A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. Results: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). Conclusion: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD. [ABSTRACT FROM AUTHOR]

Background: The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. Case presentation: Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. Conclusion: We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine tumors (NETs) are rare especially in the gallbladder. They have not been elucidated in the pathogenesis, clinicopathological characteristics, and treatment options. Case presentation: We present a 76-year-old woman with a gallbladder tumor and hepatic hilar lymph node swelling. The lymph node biopsy demonstrated neuroendocrine carcinoma (NEC). We performed cholecystectomy, hepatic hilar lymphadenectomy, extrahepatic biliary duct resection, and hepaticojejunostomy prior to chemotherapy. Pathological examination revealed the gallbladder mass was an adenocarcinoma invading to the muscular layer without any NEC components, whereas the hepatic hilar lymph nodes were filled with high-grade NEC cells with negligible area of adenocarcinoma. The patient received general chemotherapy consisting of carboplatin and etoposide, but a recurrence in the para-aortic lymph nodes occurred 4 months after surgery. Conclusions: We report a rare case of NEC of the hepatic hilar lymph nodes that were concomitant with an adenocarcinoma of the gallbladder. High-grade NEC generally has an aggressive behavior and an optimal treatment strategy should be chosen for each patient. [ABSTRACT FROM AUTHOR]

Background: Intracholecystic papillary-tubular neoplasms are rare precursor lesions of gallbladder cancer. They were proposed as a separate pathologic entity in 2012 by Adsay et al. for the unification of a variety of massforming precursor lesions including papillary adenomas, tubulopapillary adenomas, intestinal adenomas, and others. They are considered homologous to intrapapillary mucinous neoplasms of the pancreas and intrabiliary papillary neoplasms of the common bile duct. In contrast with the commoner flat-type precursor gallbladder cancer lesions, they follow a more indolent clinical course and probably different genetic pathways to carcinogenesis. They are largely uninvestigated with only a handful of studies providing biological and clinical information. Choledochal cysts are dilation of the common bile duct. Diagnosis is usually established during childhood, and only a minority of patients are diagnosed at adulthood. They are of major clinical importance as they are known predisposing factors for biliary carcinogenesis. Case presentation: The current report describes a patient with a simultaneous diagnosis of choledochal cyst and intracholecystic papillary-tubular neoplasm. The patient underwent excision of the extrahepatic biliary tree for a Todani I choledochal cyst, and histological examination of the specimen revealed an intracholecystic papillarytubular neoplasm of the gallbladder. Authors describe diagnostic and clinical course of the patient alongside clinical and biological characteristics of these rare lesions. Conclusions: To the best of our knowledge, this is the first report of a patient with a simultaneous diagnosis of choledochal cyst and intracholecystic papillary-tubular neoplasm. Those rare lesions shed light on different forms of gallbladder cancer carcinogenesis and its relationship with choledochal cysts and cholestasis. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma accounts for 90% of renal neoplasms and metastatic disease is common. One third of newly diagnosed cases will have synchronous metastases at diagnosis and further 25-50% will develop metachronous disease. Case Presentation: This study presents two new cases of gallbladder metastasis from renal cell carcinoma (RCC) from our institution and reviews the published literature. The final cohort included 52 evaluable patients. M/F ratio was 2:1 and median age was 62.5 years. Most patients were diagnosed incidentally after follow-up or staging imaging for RCC. Of the patients with available histology, all except one were clear cell type (n = 39) and 92% were polypoid. Thirty-six patients demonstrated metachronous gallbladder metastasis with median disease-free interval (DFI) from nephrectomy of 4 years. The most frequent site of metastasis was the contralateral kidney (46.7%) followed by the pancreas and lung. The median disease-free interval (DFS) after cholecystectomy was 37 months. Three- and five-year OS rates were 74 and 62%, respectively. Age younger than 45 years (p = 0.008) and DFI <24 months (p = 0.049) were associated with decreased OS. Conclusions: RCC metastasis to the gallbladder is associated with an unusual pattern of concomitant metastasis. Symptoms are not common. Simple cholecystectomy is associated with increased OS and nil local or port site recurrence. Young age and short DFI are associated with decreased OS. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is characterized by pathognomic cutaneous manifestations (heliotrope rash, periorbital edema, Gottron's papules) and proximal muscle weakness. In this paper, I will present the case of a 48-year-old female patient whose dermatomyositis was initially diagnosed as vasculitis. Following the patient's inadequate response to corticosteroid treatment, clinical and radiologic examinations were performed, showing inoperable gallbladder adenocarcinoma. Although initial chemotherapy led to regression, the dermatomyositis developed an independent course with new pathological changes leading to the progression of the disease. I will also present an overview of case reports in English published so far. Gallbladder carcinoma should be added to the list of malignancies with dermatomyositis and has to be excluded by relevant investigation in women. [ABSTRACT FROM AUTHOR]

A complete R0 resection is the standard treatment in patients with gallbladder cancer and the only potentially definitive curative therapy. Major hepatectomy, including right or extended right hepatectomy with extrahepatic bile duct resection, would be an option in patients with locally advanced gallbladder cancer, while morbidity and mortality rate are still high. Herein, we report a case of a locally advanced gallbladder cancer invading the right hepatic artery (RHA), common hepatic duct, and transverse colon. This patient was successfully treated with parenchymal sparing surgery without major hepatectomy and achieved R0 resection by means of extended cholecystectomy combined with resection of the transverse colon, extrahepatic bile duct, and RHA. Intrahepatic arterial flow was preserved without reconstruction of the RHA, and the postoperative course was favorable. Liver parenchymal sparing surgery might be an alternative procedure in patients with gallbladder cancer, to minimize the risk of severe morbidity, if R0 resection is possible. [ABSTRACT FROM AUTHOR]

Background: Gallbladder diseases present with cholelithiasis in a wide spectrum of adenomas and cancers. Two or three specimens are sampled in cholecystectomies in routine pathology practice. The aim of this study was to investigate the increase in frequency of histologic alterations in cholecystectomies, particularly precancerous lesions, by increasing the sample size to understand the carcinoma pathway. Methods: Cholecystectomies of 432 patients with pathology records and materials from two medical centers were collected, and two groups were created. Initial data with two or three samples were allocated to Group 1 and the new six samples with the initial ones were allocated to Group 2. Hematoxylin and eosin (H&E) sections were examined for histopathologic alterations, and periodic acid-Schiff (PAS) Alcian blue (pH 2.5) and high iron diamine (pH 2.5) stains were used to signify the mucin profile in case of metaplasias. For the comparison of findings, non-parametric tests, McNemar's tests, chi-squared tests and Fisher's exact test were performed. Results: Of the 432 patients, 308 (71.3%) patients were female and 124 (28.7%) patients were male. The mean age of patients was 47.9 ± 14.6 years. Cholesterolosis was observed in 95 (22%) patients in Group 1 and 108 (25%) patients in Group 2. Gallstones were detected in 255 (59%) of the cholecystectomies. There was a significant difference between Group 1 and Group 2 by increasing the sample size when we compared cholesterolosis, metaplasia and polyps (P <0.05). Cholecystitis and dysplasia rates were the same in both of the groups. There was no cancer determined. Conclusion: Increasing the sample size in cholecystectomies increased the diagnosis of some histologic alterations, but further studies with a larger number of samples over a longer period time might increase the ability to determine precancerous lesions and concomitants [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. Methods: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. Results: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. Conclusions: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC. [ABSTRACT FROM AUTHOR]

Background: Assessment of lymph node status is a critical issue in the surgical management of gallbladder cancer. The aim of this study was to compare the anatomical location of positive nodes, number of positive nodes, and lymph node ratio (LNR) as prognostic predictors in gallbladder cancer. Methods: We conducted a retrospective analysis of 135 patients with gallbladder cancer who underwent a radical resection with regional lymphadenectomy. A total of 2,245 regional lymph nodes were retrieved (median, 14 per patient). The location of positive nodes was classified according to the AJCC staging manual (7th edition). ‘Optimal’ cutoff values were determined for the number of positive nodes and LNR based on maximal χ2 scores calculated with the Cox proportional hazards regression model. Results: Lymph node metastasis was found histologically in 59 (44%) patients. The ‘optimal’ cutoff values for the number of positive nodes and LNR were determined to be three nodes and 10%, respectively. Univariate analysis identified location of positive nodes (pN0, pN1, pN2; P<0.001), number of positive nodes (0, 1 to 3, ≥4; P<0.001), and LNR (0%, 0 to 10%, >10%; P<0.001) as significant prognostic factors. Multivariate analysis identified number of positive nodes as an independent prognostic factor (P = 0.004); however, location of positive nodes and LNR failed to remain as an independent variable. Conclusions: The number of positive lymph nodes better predicts patient outcome after resection than either the location of positive lymph nodes or LNR in gallbladder cancer. Dividing the number of positive lymph nodes into three categories (0, 1 to 3, or ≥4) is valid for stratifying patients based on the prognosis after resection. [ABSTRACT FROM AUTHOR]