A deep learning model based on contrast-enhanced computed tomography for differential diagnosis of gallbladder carcinoma

Background:Gallbladder carcinoma(GBC)is highly malignant,and its early diagnosis remains difficult.This study aimed to develop a deep learning model based on contrast-enhanced computed tomography(CT)images to assist radiologists in identifying GBC.Methods:We retrospectively enrolled 278 patients with gallbladder lesions(>10 mm)who underwent contrast-enhanced CT and cholecystectomy and divided them into the training(n=194)and validation(n=84)datasets.The deep learning model was developed based on ResNet50 network.Radiomics and clinical models were built based on support vector machine(SVM)method.We comprehensively compared the performance of deep learning,radiomics,clinical models,and three radiologists.Results:Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance,HHL firstorder kurtosis,and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC,and were selected for developing radiomics model.Multivariate regression analysis revealed that age≥65 years[odds ratios(OR)=4.4,95%confidence interval(CI):2.1-9.1,P<0.001],lesion size(OR=2.6,95%CI:1.6-4.1,P<0.001),and CA-19-9>37 U/mL(OR=4.0,95%CI:1.6-10.0,P=0.003)were significant clinical risk factors of GBC.The deep learning model achieved the area under the receiver operating characteristic curve(AUC)values of 0.864(95%CI:0.814-0.915)and 0.857(95%CI:0.773-0.942)in the training and validation datasets,which were comparable with radiomics,clinical models and three radiologists.The sensitivity of deep learning model was the highest both in the training[90%(95%CI:82%-96%)]and validation[85%(95%CI:68%-95%)]datasets.Conclusions:The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

New trends in diagnosis and management of gallbladder carcinoma

Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.

Application of laparoscopic surgery in gallbladder carcinoma

Gallbladder carcinoma(GC)is a rare type of cancer of the digestive system,with an incidence that varies by region.Surgery plays a primary role in the comprehensive treatment of GC and is the only known cure.Compared with traditional open surgery,laparoscopic surgery has the advantages of convenient operation and magnified field of view.Laparoscopic surgery has been successful in many fields,including gastrointestinal medicine and gynecology.The gallbladder was one of the first organs to be treated by laparoscopic surgery,and laparoscopic cholecystectomy has become the gold standard surgical treatment for benign gallbladder diseases.However,the safety and feasibility of laparoscopic surgery for patients with GC remain controversial.Over the past several decades,research has focused on laparoscopic surgery for GC.The disadvantages of laparoscopic surgery include a high incidence of gallbladder perforation,possible port site metastasis,and potential tumor seeding.The advantages of laparoscopic surgery include less intraoperative blood loss,shorter postoperative hospital stay,and fewer complications.Nevertheless,studies have provided contrasting conclusions over time.In general,recent research has tended to support laparoscopic surgery.However,the application of laparoscopic surgery in GC is still in the exploratory stage.Here,we provide an overview of previous studies,with the aim of introducing the application of laparoscopy in GC.

Laparoscopic vs open radical resection in management of gallbladder carcinoma:A systematic review and meta-analysis

BACKGROUND Radical resection offers the only hope for the long-term survival of patients with gallbladder carcinoma(GBC)above the T1b stage.However,whether it should be performed under laparoscopy for GBC is still controversial.AIM To compare laparoscopic radical resection(LRR)with traditional open radical resection(ORR)in managing GBC.METHODS A comprehensive search of online databases,including Medline(PubMed),Cochrane Library,and Web of Science,was conducted to identify comparative studies involving LRR and ORR in GBCs till March 2023.A meta-analysis was subsequently performed.RESULTS A total of 18 retrospective studies were identified.In the long-term prognosis,the LRR group was comparable with the ORR group in terms of overall survival and tumor-free survival(TFS).LRR showed superiority in terms of TFS in the T2/tumor-node-metastasis(TNM)Ⅱstage subgroup vs the ORR group(P=0.04).In the short-term prognosis,the LRR group had superiority over the ORR group in the postoperative length of stay(POLS)(P<0.001).The sensitivity analysis showed that all pooled results were robust.CONCLUSION The meta-analysis results show that LRR is not inferior to ORR in all measured outcomes and is even superior in the TFS of patients with stage T2/TNMⅡdisease and POLS.Surgeons with sufficient laparoscopic experience can perform LRR as an alternative surgical strategy to ORR.

Gallbladder Carcinoma of the Thyroid Revealed by an Acute Festered Thyroiditis: A Literature Study about a Case

The cutaneous extension of gallbladder thyroid carcinoma is uncommon and is among the aggressive forms of the disease. We are reporting the case of a woman of 54 that shows acute festered thyroiditis worsened by a necrotic ulcer wound on the skin lasting 3 weeks amid a big neglected hetero-multinodular goitre, evolving since 20 years. The anatomopathological test showed a gallbladder thyroid carcinoma of the thyroid with severe inflammation. The treatment consisted of a complete thyroidectomy with recurrent bilateral dredging. There was a favourable evolution. Gallbladder carcinoma, in its aggressive aspect, may be linked to the occurrence of acute festered thyroiditis. Therefore, the prognosis of our patient was favourable.

Rational therapeutic strategy for T2 gallbladder carcinoma based on tumor spread

AIM:To evaluate the adequacy of surgical treatment of T2 gallbladder carcinoma(GBCa)according to tumor spread in the subserosal layer. METHODS:A series of 84 patients with GBCa were treated at Saga University Hospital,Japan between April 1989 and October 2008.The tumor stage was graded according to the TNM staging for GBCa from the American Joint Committee on Cancer Manual 6th edition. Tumor staging revealed 30 patients with T2 tumors.T2 GBCa was divided into three groups histologically by the extent of tumor spread in the subserosal layer,using a score of ss minimum(ss min),ss medium(ss med)or ss massive(ss mas). RESULTS:For ss min GBCa,there was no positive pathological factor and patient survival was satisfactory with simple cholecystectomy,with or without extra-he- patic bile duct resection.For ss med GBCa,some pathological factors,h-inf(hepatic infiltration),ly(lymphatic invasion)and n(lymph node metastasis),were positive. For ss mas GBCa,there was a high incidence of positive pathological factors.The patient group with extra-hepatic bile duct resection with D2 lymph node dissection (BDR with D2)and those with S4a5 hepatectomy had significantly better survival rates.CONCLUSION:We suggest that radical surgery is not necessary for ss min GBCa,and partial hepatectomy and BDR are necessary for both ss med and ss mas GBCa.

Relationship between pancreaticobiliary maljunction and gallbladder carcinoma: a meta-analysis

BACKGROUND: Reports on the relationship between pancreaticobiliary maljunction (PBM) and gallbladder carcinoma (GBC) are conflicting. The frequency of PBM in GBC patients and the clinical features of GBC patients with PBM vary in different studies. DATA SOURCES: English-language articles describing the association between PBM and GBC were searched in the PubMed and Web of Science databases. Nine case-control studies fulfilled the inclusion criteria and addressed the relevant clinical questions of this analysis. Data were extracted independently by two reviewers using a predefined spreadsheet. RESULTS: The incidence of PBM was higher in GBC patients than in controls (10.60% vs 1.76%, OR: 7.41, 95% CI: 5.03 to 10.87, P<0.00001). The proportion of female patients with PBM was 1.96-fold higher than in GBC patients without PBM (80.5% vs 62.9%, OR: 1.96, 95% CI: 1.09 to 3.52, P=0.12). GBC patients with PBM were 10 years younger than those without PBM (SMD: -9.90, 95% CI: -11.70 to -8.10, P<0.00001). And a difference in the incidence of associated gallstone was found between GBC patients with and without PBM (10.8% vs 54.3% OR: 0.09, 95% CI: 0.05 to 0.17, P<0.00001). Among the GBC patients with PBM, associated congenital dilatation of the common bile duct was present with a higher incidence ranging from 52.2% to 85.7%, and 70.0%-85.7% of them belonged to the P-C type of PBM (the main pancreatic duct enters the common bile duct). No substantial heterogeneity was found and no evidence of publication bias was observed.CONCLUSIONS: PBM is a high-risk factor for developing GBC, especially the P-C type of PBM without congenital dilatation of the common bile duct. To prevent GBC, laparoscopic cholecystectomy is highly recommended for PBM patients without congenital dilatation of the common bile duct, especially relatively young female patients without gallstones.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

BACKGROUND Gallbladder carcinoma(GBC)carries a poor prognosis and requires a prediction method.Gamma-glutamyl transferase–to–platelet ratio(GPR)is a recently reported cancer prognostic factor.Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear,studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases.AIM To assess the prognostic value of GPR and to design a prognostic nomogram for GBC.METHODS The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017.The patients were stratified into a high-or low-GPR group.The predictive ability of GPR was evaluated by Kaplan–Meier analysis and a Cox regression model.We developed a nomogram based on GPR,which we verified using calibration curves.The nomogram and other prognosis prediction models were compared using timedependent receiver operating characteristic curves and the concordance index.RESULTS Patients in the high-GPR group had a higher risk of jaundice,were older,and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes.Univariate analysis revealed that GPR,age,body mass index,tumor–node–metastasis(TNM)stage,jaundice,cancer cell differentiation degree,and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival(OS).Multivariate analysis confirmed that GPR,body mass index,age,and TNM stage were independent predictors of poor OS.Calibration curves were highly consistent with actual observations.Comparisons of timedependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging.CONCLUSION GPR is an independent predictor of GBC prognosis,and nomogram-integrated GPR is a promising predictive model for OS in GBC.

Surgical treatment for Nevin stage IV and V gallbladder carcinoma: report of 70 cases

BACKGROUND: The role of aggressive surgery for end-stage gallbladder carcinoma is controversial. This retrospective study was designed to evaluate the outcome of surgical treatment for Nevin stage Ⅳ and Ⅴ gallbladder carcinoma at a single institution. METHODS: A retrospective analysis was made on 70 patients with Nevin stage Ⅳ and Ⅴ gallbladder carcinoma undergoing surgical treatment from January 1993 to June 2004. RESULTS: There were 22 cases of stage Ⅳ and 48 of stage V. Cholecystectomy was performed in 37 cases with a resection rate of 53%,9 cases received radical resection, 13 extended radical resection, and 15 palliative resection. The curative resection rate was 31% and the morbidity rate was 36%. Postoperative 1-, 3-, 5-year survival rates of curative and palliative resection were 69%, 33%, 8% and 27%, 13%, 0, respectⅣely (P <0.01). The 1- and 3-year survival rates of patients undergoing exploratory laparotomy only were 3% and 0, respectively. CONCLUSIONS: Nevin stage Ⅳ and Ⅴ gallbladder carcinoma should be treated by aggressive surgery. Curative resection is promising in the improvement of long-term survⅣal rate.

Interaction among Rb/p16, Rb/E2F1 and HDAC1 Proteins in Gallbladder Carcinoma

The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line （Mz-ChA-1） were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.

Port-site metastasis of unsuspected gallbladder carcinoma with ossification after laparoscopic cholecystectomy:A case report

BACKGROUND Unsuspected gallbladder carcinoma(UGC)refers to cholecystectomy due to benign gallbladder disease,which is pathologically confirmed as gallbladder cancer during or after surgery.Port-site metastasis(PSM)of UGC following laparoscopic cholecystectomy is rare,especially after several years.CASE SUMMARY A 55-year-old man presenting with acute cholecystitis and gallstones was treated by laparoscopic cholecystectomy in July 2008.Histological analysis revealed unexpected papillary adenocarcinoma of the gallbladder with gallstones,which indicated that the tumor had spread to the muscular space(pT1b).Radical resection of gallbladder carcinoma was performed 10 d later.In January 2018,the patient was admitted to our hospital for a mass in the upper abdominal wall after surgery for gallbladder cancer 10 years ago.Laparoscopic exploration and complete resection of the abdominal wall tumor were successfully performed.Pathological diagnosis showed metastatic or invasive,moderately differentiated adenocarcinoma in fibrous tissue with massive ossification.Immunohistochemistry and medical history were consistent with invasion or metastasis of gallbladder carcinoma.His general condition was well at follow-up of 31 mo.No recurrence was found by ultrasound and epigastric enhanced computed tomography.CONCLUSION PSM of gallbladder cancer is often accompanied by peritoneal metastasis,which indicates poor prognosis.Once PSM occurs after surgery,laparoscopic exploration is recommended to rule out abdominal metastasis to avoid unnecessary surgery.

Simple cholecystectomy is an adequate treatment for grade I T1bN0M0 gallbladder carcinoma:Evidence from 528 patients

BACKGROUND T1b gallbladder carcinoma(GBC)is defined as a tumor that invades the perimuscular connective tissue without extension beyond the serosa or into the liver.However,controversy still exists over whether patients with T1b GBC should undergo cholecystectomy alone or radical GBC resection.AIM To explore the optimal surgical approach in patients with T1b gallbladder cancer of different pathological grades.METHODS Patients with T1bN0M0 GBC who underwent surgical treatment between 2000 and 2017 were included in the Surveillance,Epidemiology,and End Results database.The Kaplan-Meier method and log-rank test were used to analyze the overall survival(OS)and disease-specific survival(DSS)of patients with T1b GBC of different pathological grades.Cox regression analysis was used to identify independent predictors of mortality and explore the selection of surgical methods in patients with T1b GBC of different pathological grades and their relationship with prognosis.RESULTS Of the 528 patients diagnosed with T1bN0M0 GBC,346 underwent simple cholecystectomy(SC)(65.5%),131 underwent SC with lymph node resection(SC+LN)(24.8%),and 51 underwent radical cholecystectomy(RC)(9.7%).Without considering the pathological grade,both the OS(P<0.001)and DSS(P=0.003)of T1b GBC patients who underwent SC(10-year OS:27.8%,10-year DSS:55.1%)alone were significantly lower than those of patients who underwent SC+LN(10-year OS:35.5%,10-year DSS:66.3%)or RC(10-year OS:50.3%,10-year DSS:75.9%).Analysis of T1b GBC according to pathological classification revealed no significant difference in OS and DSS between different types of procedures in patients with grade Ⅰ T1b GBC.In patients with grade Ⅱ T1b GBC,obvious survival improvement was observed in the OS(P=0.002)and DSS(P=0.039)of those who underwent SC+LN(10-year OS:34.6%,10-year DSS:61.3%)or RC(10-year OS:50.5%,10-year DSS:78.8%)compared with those who received SC(10-year OS:28.1%,10-year DSS:58.3%).Among patients with grade Ⅲ or Ⅳ T1b GBC,SC+LN(10-year OS:48.5%,10-year DSS:72.2%),and RC(10-year OS:80%,10-year DSS:80%)benefited OS(P=0.005)and DSS(P=0.009)far more than SC(10-year OS:20.1%,10-year DSS:38.1%)alone.CONCLUSION Simple cholecystectomy may be an adequate treatment for grade Ⅰ T1b GBC,whereas more extensive surgery is optimal for grades Ⅱ-Ⅳ T1b GBC.

The relationship between surgery and prognosis of gallbladder carcinoma

OBJECTIVE: To explore the prognostic factors of gallbladder carcinoma and the relationship between operative procedure and prognosis of gallbladder carcinoma. METHOD: A retrospective clinical analysis was made in 56 patients with gallbladder carcinoma who had undergone surgery at our department from 1995 to 2001. RESULTS: Of the 56 patients, 20 were men and 36 women with a male to female ratio of 1:1. 56. Their age ranged from 41 to 79 years with a mean of 59.6 years, Thirty-four patients suffered from gallstones. Abdominal pain (83.9%) and jaundice (41.1%) were the main symptoms. Thirty patients (Nevin stage Ⅱ in 5 patients, Ⅲ in 3, Ⅳ in 4, and Ⅴ in 18) received radical or extended radical resection; non-radical resection was performed in 11 patients of Nevin stage Ⅴ; and 15 patients of Nevin stage Ⅴ were subjected to biopsy with or without palliative bypass procedure. Statistical analysis showed that operative procedure, staging of Nevin, and gallstone affected significantly postoperative survival, but age, sex, preoperative serum bilirubin level, numbers of tumor location, histopathological type and grade were not significant prognostic factors. After radical resection was classified with Nevin staging, we found that all the patients of stage Ⅱ were alive. Meanwhile the postoperative survival periods of radical resection groups of stage Ⅲ to Ⅴ, palliative resection group, and biopsy with/without palliative drainage group were statistically different. CONCLUSIONS: From Nevin stage Ⅱ to Ⅴ, the survival period of respective stage group, which treated with curative operation, became shorter gradually. In those patients of stage Ⅴ, the survival period of curative operation group was longer than that of palliative resection group, and that of the latter was better than that of biopsy with/without palliative drainage group. So radical resection was still the unique way to better prognosis.

Subcutaneous and breast metastasis from asymptomatic gallbladder carcinoma

BACKGROUND:Though gallbladder carcinoma is asso- ciated with early lymphatic and hematogenous spread, the only common extra-abdominal site of metastasis is lung.Gallbladder carcinoma metastasizing to breast and subcutaneous tissue is not known. METHOD:This report describes an interesting and unusual case of asymptomatic gallbladder carcinoma presenting with subcutaneous and breast metastasis. RESULTS:A 42-year-old woman presented with multiple subcutaneous nodules over the abdominal wall,anterior chest wall,back and in bilateral breasts.Fine needle aspiration cytology(FNAC)of these nodules revealed metastatic adenocarcinoma.The patient was investigated for a primary neoplasm.An ultrasound of the abdomen followed by a contrast-enhanced CT scan showed a growth in gallbladder,infiltrating the liver with multiple hepatic metastases.CT-guided FNAC from the growth in the gallbladder revealed adenocarcinoma.She was diagnosed as a case of metastatic adenocarcinoma of the gallbladder and palliative combination chemotherapy with gemcitabine and carboplatin was given.But she developed jaundice and deteriorated dramatically in a short span of time.No specific therapy could be started and she was given supportive treatment.She died within three weeks of diagnosis due to hepatic encephalopathy. CONCLUSIONS:This report highlights an unusual metastasis of gallbladder carcinoma to the breast and subcutaneous tissue presenting as multiple lesions,which has never been reported in the English literature.These were unknown sites of metastasis for carcinoma of the gallbladder.Moreover,bilateral multiple metastatic lesions to breast are also very rare.

Early diagnosis of primary gallbladder carcinoma

Objective: To improve early diagnosis of primary gallbladder carcinoma (PGC) and the understanding of its pathogenesis, pathological stages and progno- sis. Methods: The data from 679 patients with PGC trea- ted in our hospital from 1956 to 1998 were analyzed retrospectively. Results: The incidence of PGC has been increasing in recent years, and the treatment is not satisfactory. Upon diagnosis, most patients with PGC were at ad- vanced stage. PGC was usually found in elderly women. The ratio of man to woman was 1:3. The gallstone, closely related to PGC, was found in 60% of the patients with PGC. The diagnostic accordance rate before and after operation was Iow. In most pa- tients, PGC was found unexpectedly during opera- tion for gallstone or acute cholecystitis. Many pa- tients with PGC missed the opportunity of diagnosis and therapy because doctor only noticed the diagnosis of gallstone. Pathological classification revealed that PGC in most patients (84.4%) were adenocarcino- ma. Imaging helped to find early-stage cases and im- prove prognosis. Conclusions: Understanding of pathogenesis, patho- logical stages and prognosis of PGC and proper use of various examinations are essential to the early di- agnosis and treatment of the disease.

ANALYSIS OF P53 AND VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTOR Flk-1 EXPRESSION IN HUMAN GALLBLADDER CARCINOMA FOR DETERMINATION OF TUMOR VASCULARITY

Objective： More and more studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. There is some evidence that p53 mutations cause overexpression of vascular endothelial growth factor （VEGF）, a major inducer of angiogenesis. In addition, there is now growing evidence that several malignancies express receptors for VEGF, especially receptor-2 （Flk-1/KDR）, raising the possibility that the VEGF/VEGF receptor axis may serve as an autocrine pathway in some tumors. We examined the expression of p53 and VEGF and its receptor FlK-1, together with microvessel count （MVC） to investigate the role of VEGF as an angiogenic marker, the presence of VEGF/Flk-1 axis, and the possible role of p53 in the regulation of angiogenesis in human gallbladder carcinoma. Methods： Surgically resected specimens of 49 gallbladder carcinomas were studied by immunohistochemical staining for p53 protein, VEGF, Flk-1 and factor VIII-related antigen. VEGF expression and mutant p53 expression were then correlated with Nevin stage, differentiation grade, MVC, and lymph nodes metastasis. Results： VEGF, Flk-1 expression and positive p53 protein accumulation and BEGF expression was found in 63.3%, 67.3% and 61.2% of tumors, respectively. The expression of Flk-1 was markedly correlated with VEGF （P〈0.05）. The percentage of the patients with both positive VEGF and Flk-1 expressions was 49.0% （24/49）, and their MVC value was markedly higher than that of the others. P53 and VEGF staining status were identical in 55.1% of tumors. The Nevin staging of p53-or VEGF-positive tumors was significantly later than negative tumors. The MVC in p53-or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-negative tumors was significantly lower than that in the other subgroups. Conclusion： The findings suggest the VEGF/F1 k- 1 axis and p53-VEGF pathway tumor angiogenesis in human gallbladder carcinoma. Combined analysis of p53 and VEGF expression, plus Flk-1 and VEGF expression might be useful for predicting the tumor vacularity and biologic behaviors of gallbladder cancer.

Simultaneous breast and ovarian metastasis from gallbladder carcinoma

BACKGROUND:Gallbladder carcinoma is a common malignancy in the Indian subcontinent.It commonly metastasizes through lymphatics,direct invasion,and hematogenous spread.A common extra-abdominal site of metastasis is the lungs.Simultaneous metastasis to breast and ovary is extremely rare.METHOD:This report describes an unusual case of carcinoma gallbladder metastasizing to the breast and ovary at the same time.RESULTS:A 45-year-old woman came to us with complaints of flatulent dyspepsia associated with weight loss and anorexia.Ultrasound of the abdomen revealed hepatomegaly with thick-walled gallbladder with multiple stones and a mass at the fundus,but normal uterus and ovary.Contrast-enhanced computer tomography of the abdomen showed a gallbladder mass infiltrating the liver parenchyma.The patient underwent radical cholecystectomy.Histopathological examination revealed a poorly-differentiated adenocarcinoma with margins free from tumor infiltration.One month after surgery she developed a breast lump.Ultrasound of the abdomen for metastatic workup revealed an ovary mass.Simple mastectomy and salphingo-opherectomy were performed,and histopathological examination revealed a metastatic adenocarcinoma.The patient is now on chemotherapy with gemcitabin.CONCLUSION:This is an unusual case of carcinoma of the gallbladder with metastasis to the breast and ovary,which has not been documented before.

Synchronous primary duodenal papillary adenocarcinoma and gallbladder carcinoma:A case report and review of literature

BACKGROUND Synchronous primary cancers(SPCs) have become increasingly frequent over the past decade.However,the coexistence of duodenal papillary and gallbladder cancers is rare,and such cases have not been previously reported in the English literature.Here,we describe an SPC case with duodenal papilla and gallbladder cancers and its diagnosis and successful management.CASE SUMMARY A 68-year-old Chinese man was admitted to our hospital with the chief complaint of dyspepsia for the past month.Contrast-enhanced computed tomography of the abdomen performed at the local hospital revealed dilatation of the bile and pancreatic ducts and a space-occupying lesion in the duodenal papilla.Endoscopy revealed a tumor protruding from the duodenal papilla.Pathological findings for the biopsied tissue revealed tubular villous growth with moderate heterogeneous hyperplasia.Surgical treatment was selected.Macroscopic examination of this surgical specimen revealed a 2-cm papillary tumor and another tumor protruding by 0.5 cm in the gallbladder neck duct.Intraoperative rapid pathology identified adenocarcinoma in the gallbladder neck duct and tubular villous adenoma with high-grade intraepithelial neoplasia and local canceration in the duodenal papilla.After an uneventful postoperative recovery,the patient was discharged without complications.CONCLUSION It is essential for clinicians and pathologists to maintain a high degree of suspicion while evaluating such synchronous cancers.

Mechanism of apoptosis induced by Mcl-1 inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells

Objective:To investigate the mechanism of apoptosis induced by myeloid cell leukemia-1(Mcl-1)inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells.Methods:GBC-SD cells were treated with different concentrations of UMI-77.GBC-SD cell proliferation and apoptosis were detected by MTT assay and Annexin V/PI.The expressions of Mcl-1,Bcl-2,Bcl-xL,Bax,Bak,cleaved-caspase 9,cleaved-caspase 3 and cleaved-PARP proteins in GBC-SD cells treated with UMI-77 were detected by Western blotting.Results:The results of MTT showed that different concentrations of UMI-77 had different inhibitory effects on cell proliferation of GBC-SD cells in a dose-dependent and time-dependent manner.Annexin V/PI results showed that the apoptosis rate was increasing gradually with the increase of UMI-77 concentration in a dose-dependent manner.Western blotting results showed that the expression of anti-apoptotic protein Mcl-1 was significantly decreased(p<0.05),and the expressions of Bax and Bak proteins were significantly increased respectively(p<0.05),but there were no significant changes in the expressions of Bcl-2 and Bcl-xL proteins,and the expression levels of cleaved-caspase 9,cleaved-caspase 3 and cleaved-PARP proteins were significantly increased(p<0.05)in 24 h after GBC-SD cells were treated with 10μmol/L of UMI-77.Conclusions:Mcl-1 inhibitor UMI-77 can induce the apoptosis of GBC-SD cells in a dose-dependent manner through the caspase-mediated endogenous apoptosis pathway.Therefore,Mcl-1 may become a new therapeutic target in the research on gallbladder cancer.

Gallbladder carcinoid masquerading as gallbladder carcinoma

BACKGROUND:Carcinoid of the gallbladder is rare.Since it often presents as a gallbladder mass it may be confused with gallbladder carcinoma. METHODS:A 35-year-old lady presented with pain in the right upper abdomen,and was radiologically found to have a gallbladder mass.A provisional diagnosis of gallbladder carcinoma was made.Laparotomy revealed a 20×20 cm, exophytic,friable growth arising from the fundus of the gallbladder.It was excised with segmentⅣb andⅤof the liver and regional lymphadenectomy. RESULT:Histopathological examination revealed it was a neuroendocrine carcinoma,atypical carcinoid of the gallbladder. CONCLUSION:Gallbladder carcinoid has a poor outcome, requires aggressive treatment,and should be considered as one of the rare but possible gallbladder lesions.