• factors
• gallbladder cancer
• hospitalization
• national inpatient sample
• palliative care
• prevalence

• Humans
• Palliative Care/statistics & numerical data
• Female
• Male
• Aged
• Middle Aged
• Retrospective Studies
• Gallbladder Neoplasms/therapy
• Gallbladder Neoplasms/epidemiology
• United States/epidemiology
• Hospitalization/statistics & numerical data
• Prevalence
• Patient Acceptance of Health Care/statistics & numerical data
• Aged, 80 and over
• Inpatients/statistics & numerical data
• Adult
• Medicare/statistics & numerical data

• CanPatrol® technique
• Chemotherapy
• Circulating tumor cells (CTCs)
• Gallbladder adenocarcinoma
• Immunotherapy
• Tumor treatment response

• Humans
• Neoplastic Cells, Circulating/pathology
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/blood
• Gallbladder Neoplasms/mortality
• Gallbladder Neoplasms/therapy
• Female
• Male
• Adenocarcinoma/pathology
• Adenocarcinoma/blood
• Adenocarcinoma/mortality
• Adenocarcinoma/therapy
• Middle Aged
• Aged
• Prognosis
• Adult
• Biomarkers, Tumor/blood
• Neoplasm Staging
• Aged, 80 and over

• 81703767 National Natural Science Foundation of China
• 2019JJ50891 Hunan Natural Science Foundation of China

• Best supportive care
• Palliation in biliary malignancy
• Palliative care

• Humans
• Palliative Care/methods
• Biliary Tract Neoplasms/therapy
• Biliary Tract Neoplasms/diagnosis

• Carcinoma
• Gallbladder neoplasms
• Magnetic resonance imaging
• Prognosis
• Survival

• Humans
• Gallbladder Neoplasms/diagnostic imaging
• Gallbladder Neoplasms/surgery
• Gallbladder Neoplasms/mortality
• Gallbladder Neoplasms/pathology
• Nomograms
• Female
• Male
• Retrospective Studies
• Aged
• Magnetic Resonance Imaging/methods
• Middle Aged
• Preoperative Care/methods
• Prognosis
• Survival Rate

• 3D bioprinting
• gallbladder carcinoma
• in vitro model
• intratumoral heterogeneity
• tumor microenvironment

• Humans
• Tumor Microenvironment
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/metabolism
• Bioprinting
• Printing, Three-Dimensional
• Cell Line, Tumor
• Macrophages/metabolism
• Macrophages/pathology
• Macrophages/cytology
• Cell Proliferation

• CanPatrol® technique
• Circulating tumor cells (CTCs)
• Gallbladder adenocarcinoma
• Prognosis
• Surgical resection

• Humans
• Neoplastic Cells, Circulating/pathology
• Gallbladder/pathology
• Prognosis
• Adenocarcinoma/surgery
• Risk Factors

• 81703767 National Natural Science Foundation of China
• 2019JJ50891 Hunan Natural Science Foundation of China

• Gallbladder carcinoma
• Gallbladder neoplasms
• Staging laparoscopy

• Curative-intent resection
• Gallbladder adenocarcinoma
• Gallbladder mucinous adenocarcinoma
• Prognosis

• Humans
• Lymphatic Metastasis
• Retrospective Studies
• Adenocarcinoma, Mucinous/surgery
• Adenocarcinoma, Mucinous/pathology
• Adenocarcinoma/surgery
• Adenocarcinoma/pathology
• Gallbladder Neoplasms/surgery
• Gallbladder Neoplasms/pathology
• Carcinoma, Signet Ring Cell/pathology
• Prognosis
• Neoplasm Staging

• West China Hospital, Sichuan University
• Sichuan University
• Sichuan Province Science and Technology Support Program
• China Postdoctoral Science Foundation
• Fundamental Research Funds for the Central Universities

Introduction

Incidental discovery of gallbladder cancer (GBC) on postoperative histopathology or intra-operative suspicion is becoming increasingly frequent since laparoscopic cholecystectomy became the standard of care for gallstone disease. Incidental GBC (IGBC) portends a better survival than primarily detected GBC. Various factors affect the outcome of re-resection with the timing of re-intervention an important determinant of survival.

Methods

All patients of IGBC who underwent curative resection from January 2009 to December 2018 were considered for analysis. Details of demographic profile, index surgery, and operative findings on re-resection, histopathology and follow-up were retrieved from the prospectively maintained database. Patients were evaluated in three groups based on the interval between index cholecystectomy and re-resection: Early (<4 weeks), Intermediate (4-12 weeks) and Late (>12 weeks), using appropriate statistical tests.

Results

Ninety-one patients were admitted with IGBC during the study period of which 48 underwent re-resection with curative intent. The median age of presentation was 55 years (31-77 years). The median duration of follow-up was 40.6 months (Range: 1.2-130.6 months). Overall and disease-free survival among the above-mentioned three groups was the best in the early group (104 and 102 months) as compared to the intermediate (84 and 83 months) and late groups (75 and 73 months), though the difference failed to achieve statistical significance (p=0.588 and 0.581). On univariate analysis, factors associated with poor outcome were node metastasis, need for common bile duct (CBD) excision and high-grade tumor. However, on multivariate analysis, poor differentiation was the only independent factor affecting survival.

Conclusion

Early surgery, preferably within four weeks, possibly entails better survival in incidentally detected GBC. The grade of a tumor, however, is the most important determinant of survival in IGBC.

• Cholangiocarcinoma
• Gall bladder cancer
• Hepatocellular cancer
• Pancreatic cancer

• Fluorodeoxyglucose F18
• Humans
• Neoplasm Staging
• Pancreatic Neoplasms/diagnostic imaging
• Positron Emission Tomography Computed Tomography
• Positron-Emission Tomography/methods
• Radiopharmaceuticals
• Pancreatic Neoplasms

Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circβ-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circβ-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circβ-catenin overexpression had the opposite effects. In vivo, silencing of circβ-catenin inhibited tumor growth. Furthermore, we also found that circβ-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circβ-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circβ-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circβ-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circβ-catenin might be a potential therapeutic strategy for GBC.

• Carcinoma
• Gallbladder
• Neoplasm
• Survival
• Tomography

• Aged
• Female
• Gallbladder Neoplasms/diagnostic imaging
• Gallbladder Neoplasms/surgery
• Humans
• Male
• Nomograms
• Prognosis
• Retrospective Studies
• Tomography, X-Ray Computed

• 1 CSRD VA
• 1 CSRD VA

The p53-upregulated modulator of apoptosis (PUMA) has been reported to be involved in various types of cancer. However, its potential biological role in gallbladder carcinoma (GBC) has not been fully elucidated. The present study aimed to determine the expression levels of PUMA and its biological effects on GBC. The mRNA and protein expression levels of PUMA in GBC tissues and cell lines were measured using reverse transcription-quantitative PCR and western blotting, respectively. The effects of PUMA overexpression on cell viability, proliferation and invasive ability were determined in vitro using the MTT, colony formation and Transwell invasion assays, respectively. The apoptotic rates were detected using the Annexin V-FITC apoptosis detection kit. Furthermore, follow-up of patients with GBC was performed to identify the association between PUMA expression levels and GBC prognosis. The results of the present study demonstrated that the expression levels of PUMA were significantly lower in the GBC tissues and cell lines compared with those in adjacent normal gallbladder tissues and normal gallbladder cells, respectively. Further experiments indicated that overexpression of PUMA inhibited the viability, proliferation and invasive ability of GBC cells compared with those in the control-transfected GBC cells. In addition, overexpression of PUMA significantly promoted apoptosis in GBC cells. Furthermore, overexpression of PUMA inhibited epithelial-mesenchymal transition, and promoted Bax upregulation and Bcl-2 downregulation compared with those in the control group. Low PUMA expression levels were associated with a short overall survival time in patients with GBC. In conclusions, PUMA may act as a tumor suppressor in GBC and may serve as a potential novel treatment target for human GBC.

• Bax/Bcl-2
• epithelial-mesenchymal transition
• gallbladder carcinoma
• molecular mechanism
• p53-upregulated modulator of apoptosis

Laparoscopic cholecystectomy (LC) has been widely used in the treatment of gallbladder diseases. Since the indications for operation are constantly expanding, the intraoperative or postoperative incidence of unexpected gallbladder carcinoma (UGC) is gradually increasing. The incidence of UGC in LC and open cholecystectomy is 2.09% and 0.91%, respectively. Because gallbladder carcinoma is often accompanied by gallstones or inflammation and lacks specific clinical manifestations, imaging features, and specific serum tumor markers, the preoperative diagnostic rate of gallbladder carcinoma is only 30%, and 30% of cases of gallbladder carcinoma are diagnosed intraoperatively or postoperatively. Pathological T stage, lymph node metastasis, and gallbladder rupture are independent risk factors for the prognosis of patients with UGC. Preoperative imaging combined with serological tumor markers, intraoperative careful exploration, and rapid pathological examination are important measures to reduce the misdiagnosis and missed diagnosis of UGC. For patients with benign gallbladder diseases with a high potential of canceration, performing cholecystectomy in time and strictly grasping the indications for preserving gallbladder for benign gallbladder diseases are important preventive measures to reduce the incidence of UGC.

• Unexpected gallbladder carcinoma
• Misdiagnosis and missed diagnosis
• Causes
• Treatment
• Strategy
• Prevention

• Dotatate
• FDG
• HCC
• Hepatobiliary
• PET/MRI

• Gallbladder cancer
• Gallbladder neoplasms
• Lymph node excision
• Lymphadenectomy
• Survival

• Gallbladder neoplasms
• Lymph node excision
• Surgery
• Surveillance, epidemiology, and end results
• Survival

• Gallbladder
• Multidetector computed tomography
• Neoplasm
• Residual tumor
• Survival

• Aged
• Aged, 80 and over
• Female
• Gallbladder/diagnostic imaging
• Gallbladder/surgery
• Gallbladder Neoplasms/diagnostic imaging
• Gallbladder Neoplasms/surgery
• Humans
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm, Residual
• Preoperative Care/methods
• Prognosis
• Reproducibility of Results
• Retrospective Studies
• Sensitivity and Specificity
• Survival Analysis
• Tomography, X-Ray Computed/methods

• Gallbladder cancer
• Gallbladder inflammatory diseases
• Prognosis
• Real-Time PCR
• miRNA 335-5p

• Gallbladder cancer
• Multi-organ resection
• Palliative chemotherapy
• Resectability rate

• carbohydrate antigen 19-9
• gallbladder carcinoma
• resectability

• Bayesian network model
• TNM stage
• gallbladder adenocarcinoma
• predictive model
• surgery

Radical resection is an effective therapeutic method to increase the survival rate of patients with gallbladder cancer (GBC). In addition to the surgical approach, the relationships between various clinicopathologic factors and the outcome of patients with GBC remain controversial.

Clinical and laboratory examination characteristics, pathological and surgical data, and post-operative survival time of 338 patients with advanced GBC who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University, China from January 2008 to December 2012 were analyzed retrospectively. Factors influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analysis.

The overall survival rates for curative resection patients were significantly greater than those for non-curative resection patients (1-,3-,5-year survival rate and mean-survival time: 59.0%, 47.3%, 44.3% and 22.0 months vs. 12.7%, 8.3%, 7.7% and 3.0 months) (P < 0.001). For the curative resection patients, positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites were all independent risk factors for poor prognosis. For patients with T3 stage, neither segmentectomy of IVb and V nor common bile duct resection improved the prognosis (P = 0.867 and P = 0.948). For patients with T4 stage, aggressive curative resection improved the prognosis (P = 0.007).

An advanced T stage does not preclude curative resection. Positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites are all independent risk factors for poor prognosis in the curative intent resection patients. The range of liver resection and whether common bile duct resection is performed do not influence the prognosis as long as R0 resection is achieved.

• Gallbladder
• Metachronous neoplasms
• Neoplasm metastases
• Renal cell carcinoma
• Therapeutics

• Aged
• Carcinoma, Renal Cell/diagnosis
• Carcinoma, Renal Cell/secondary
• Carcinoma, Renal Cell/surgery
• Gallbladder Neoplasms/diagnosis
• Gallbladder Neoplasms/secondary
• Gallbladder Neoplasms/surgery
• Humans
• Kidney Neoplasms/diagnosis
• Kidney Neoplasms/surgery
• Male
• Neoplasms, Second Primary/diagnosis
• Neoplasms, Second Primary/surgery
• Rare Diseases/diagnosis
• Rare Diseases/surgery
• Treatment Outcome

Gallbladder carcinoma with peritoneal metastasis has a poor prognosis, with a median survival time of 4.8 months. We report the survival of a patient with gallbladder carcinoma with peritoneal metastasis for 7.6 months owing to treatment with tumor resection after chemoradiotherapy.

A 69-year-old man was referred to our hospital for gallbladder carcinoma with hepatic invasion. Cholecystectomy was performed along with S4a and S5 hepatectomy and extrahepatic bile duct resection with lymph node dissection. The postoperative pathological diagnosis was moderately differentiated adenocarcinoma, T3, N0, M0, stage IIIA by the International Union Against Cancer TNM classification. Despite treatment with gemcitabine, the common hepatic artery and para-aortic lymph nodes showed metastases after 3 months from surgery. Although a combination of cisplatin, gemcitabine, and radiotherapy reduced the size of the lymph node metastasis, the peritoneal metastasis persisted. The peritoneal metastasis responded to chemoradiotherapy using tegafur-uracil and leucovorin, but it recurred. The metastasis was resected after 3 years and 9 months from the first surgery, and chemotherapy was discontinued. Seven years and 6 months after the initial surgery, the patient exhibited no signs of tumor recurrence or metastasis.

Multidisciplinary treatment including resection without residual tumors could achieve complete remission of gallbladder carcinoma with lymph node and peritoneal metastases in the selected patient.

• Chemoradiotherapy
• Gallbladder carcinoma
• Long-term survival
• Multidisciplinary treatment
• Peritoneal metastasis
• Resection

The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma’’ (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.

• Gallbladder carcinoma
• Stage-adjusted therapy
• Radical cholecystectomy
• Gallbladder polyps
• Cholecystitis
• Gallstones
• Laparoscopic cholecystectomy

• Carcinoma/mortality
• Carcinoma/pathology
• Carcinoma/surgery
• Cholecystectomy/adverse effects
• Cholecystectomy/mortality
• Gallbladder Neoplasms/mortality
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/surgery
• Humans
• Neoplasm Staging
• Risk Factors
• Treatment Outcome

• Best supportive care
• Gallbladder cancer
• Overall survival
• Palliative chemotherapy

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemoradiotherapy
• Combined Modality Therapy
• Female
• Gallbladder Neoplasms/drug therapy
• Gallbladder Neoplasms/epidemiology
• Gallbladder Neoplasms/surgery
• Humans
• Male
• Middle Aged
• Poland/epidemiology
• Survival Rate
• Treatment Outcome

• Adenocarcinoma
• Cholelithiasis
• Gallbladder cancer
• Imaging
• Loco-regional and distant spread

AIM: To clarify whether the performance of liver resections (LR) for incidental gallbladder carcinoma (IGBC)’s depends more on the experience of the hospitals in liver surgery than on complying with the guidelines in Germany.

METHODS: For data analysis, we used the Surgical Association of Endoscopy and Ultrasound and Minimally Invasive Surgery Central Registry of “IGBC” of the German Society of Surgery (the German Registry). In 2010, we started a second form by requesting the frequency of LR at the various hospitals in Germany. The indication for LR was irrelevant. The aim was to determine the overall frequency of liver resections at the hospitals. We divided the hospitals according to their experience in liver surgery into high- (HV), mid- (MV), and low-volume (LV) LR hospitals.

RESULTS: This study includes 487 IGBC’s from 167 centers. There were 36 high-volume, 32 mid-volume, and 99 low-volume centers. In the high-volume centers, the mean (range) number of liver resections was 101 (40-300). In the mid-volume centers, the mean (range) number of liver resections was 26 (20-39). In the low-volume centers, the mean (range) number of liver resections was 6.5 (0-19) (P < 0.001). LV’s perform LR for T2-3 gallbladder carcinomas significantly less often than high-volume or mid-volume centers (χ² = 13.78, P = 0.001). In HV’s and MV’s, 61% of the patients with an indication for liver resection underwent LR, but in LV centers, only 41% with an indication for LR underwent LR (P < 0.001). In cases of T1b carcinomas, LR was performed significantly more often in HV’s (P = 0.009).

CONCLUSION: The central problem is that the performance of the required liver resection in IGBC in Germany depends on the hospital experience in liver surgery and not on the recommendations of the German guidelines.

• Gallbladder carcinoma
• Radical cholecystectomy
• High-volume center
• German-registry
• Volume cut-off
• Hepatobiliary surgery

• Carcinoma/surgery
• Gallbladder Neoplasms/surgery
• Germany
• Guideline Adherence/trends
• Hepatectomy/standards
• Hepatectomy/trends
• Hospitals, High-Volume/standards
• Hospitals, High-Volume/trends
• Hospitals, Low-Volume/standards
• Hospitals, Low-Volume/trends
• Humans
• Practice Guidelines as Topic
• Practice Patterns, Physicians'/standards
• Practice Patterns, Physicians'/trends
• Retrospective Studies

Gallbladder cancer (GBC) shows a marked geographical variation in its incidence. Middle-aged and elderly women are more commonly affected. Risk factors for its development include the presence of gallstones, chronic infection and pancreaticobiliary maljunction. Controversy remains in regard to the theory of carcinogenesis from adenomyomatosis, porcelain gallbladder and adenoma of the gallbladder. The surgical strategy and prognosis after surgery for GBC differ strikingly according to T-stage. Discrimination of favorable cases, particularly T2 or T3 lesions, is useful for the selection of surgical strategies for individual patients. Although many candidate factors predicting disease progression, such as depth of subserosal invasion, horizontal tumor spread, tumor budding, dedifferentiation, Ki-67 labeling index, p53 nuclear expression, CD8+ tumor-infiltrating lymphocytes, mitotic counts, Laminin-5-gamma-2 chain, hypoxia-inducible factor-1a, cyclooxygenase-2 and the Hedgehog signaling pathway have been investigated, useful prognostic makers or factors have not been established. As GBC is often discovered incidentally after routine cholecystectomy and accurate preoperative diagnosis is difficult, close mutual cooperation between surgeons and pathologists is essential for developing a rational surgical strategy for GBC.

• Gallbladder cancer
• Surgical strategy
• Pathology
• Prognostic factors

• P-glycoprotein
• gallbladder cancer
• glutathione S-transferase
• metastasis
• prognosis

• Adenocarcinoma/diagnosis
• Adult
• Aged
• Aged, 80 and over
• Cholecystectomy, Laparoscopic
• Cholelithiasis/surgery
• Female
• Gallbladder Neoplasms/diagnosis
• Humans
• Incidental Findings
• Male
• Middle Aged
• Young Adult

• Aetiology
• Chronic inflammation
• Gallbladder cancer
• Pathogenesis

• Adult
• Aged
• Aged, 80 and over
• Cholecystectomy
• Female
• Gallbladder Neoplasms/diagnosis
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/surgery
• Humans
• Laparoscopy/instrumentation
• Laparotomy
• Male
• Middle Aged
• Neoplasm Staging
• Prospective Studies

The surgical strategy for gallbladder cancer (GBC) depends on the extent of the disease. Thus, the identification of useful prognostic markers exerting strong prognostic impact for each T stage would be beneficial in the development of rational therapeutic strategies. The purpose of this study was to identify useful prognostic markers of GBC for each T stage. CD8⁺ tumor-infiltrating lymphocytes (TIL), Ki-67 labeling index (LI), p53 nuclear expression and mitotic count (MC) were investigated as candidate prognostic markers. In total, 86 patients with invasive GBC were included. Of the prognostic markers examined, only MC showed a correlation with reduced survival (P=0.0383) in the univariate analysis of overall T stage. In the univariate analysis of T2 stage (n=31), only high p53 expression correlated with survival showing a positive correlation (P=0.0154). In the univariate analysis of T3 stage (n=40), the only factor showing a significant correlation with survival was MC (P=0.0113). Multivariate analysis, including N and M as factors, identified only MC as an independent prognostic factor in T3 stage GBC (P=0.0419). In conclusion, this study demonstrated the strong prognostic impact of MC in GBC, particularly in patients with T3 tumor.

• Ki-67 labeling index
• gallbladder cancer
• mitotic counts
• p53
• tumor infiltrative lymphocyte

• Aged
• Aged, 80 and over
• Biopsy, Needle
• Carcinoma/epidemiology
• Carcinoma/pathology
• Carcinoma/surgery
• Cholecystectomy/methods
• Cohort Studies
• Disease-Free Survival
• Female
• Gallbladder Neoplasms/epidemiology
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/surgery
• Germany/epidemiology
• Humans
• Immunohistochemistry
• Incidence
• Kaplan-Meier Estimate
• Lymph Nodes/pathology
• Male
• Middle Aged
• Neoplasm Invasiveness/pathology
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Risk Assessment
• Statistics, Nonparametric
• Survival Analysis
• Tomography, X-Ray Computed/methods
• Treatment Outcome