BACKGROUND Gallbladder cancer(GBC)is the most common malignant tumor of the biliary system,and is often undetected until advanced stages,making curative surgery unfeasible for many patients.Curative surgery remains th...BACKGROUND Gallbladder cancer(GBC)is the most common malignant tumor of the biliary system,and is often undetected until advanced stages,making curative surgery unfeasible for many patients.Curative surgery remains the only option for long-term survival.Accurate postsurgical prognosis is crucial for effective treatment planning.tumor-node-metastasis staging,which focuses on tumor infiltration,lymph node metastasis,and distant metastasis,limits the accuracy of prognosis.Nomograms offer a more comprehensive and personalized approach by visually analyzing a broader range of prognostic factors,enhancing the precision of treatment planning for patients with GBC.AIM A retrospective study analyzed the clinical and pathological data of 93 patients who underwent radical surgery for GBC at Peking University People's Hospital from January 2015 to December 2020.Kaplan-Meier analysis was used to calculate the 1-,2-and 3-year survival rates.The log-rank test was used to evaluate factors impacting prognosis,with survival curves plotted for significant variables.Single-factor analysis revealed statistically significant differences,and multivariate Cox regression identified independent prognostic factors.A nomogram was developed and validated with receiver operating characteristic curves and calibration curves.Among 93 patients who underwent radical surgery for GBC,30 patients survived,accounting for 32.26%of the sample,with a median survival time of 38 months.The 1-year,2-year,and 3-year survival rates were 83.87%,68.82%,and 53.57%,respectively.Univariate analysis revealed that carbohydrate antigen 19-9 expre-ssion,T stage,lymph node metastasis,histological differentiation,surgical margins,and invasion of the liver,ex-trahepatic bile duct,nerves,and vessels(P≤0.001)significantly impacted patient prognosis after curative surgery.Multivariate Cox regression identified lymph node metastasis(P=0.03),histological differentiation(P<0.05),nerve invasion(P=0.036),and extrahepatic bile duct invasion(P=0.014)as independent risk factors.A nomogram model with a concordance index of 0.838 was developed.Internal validation confirmed the model's consistency in predicting the 1-year,2-year,and 3-year survival rates.CONCLUSION Lymph node metastasis,tumor differentiation,extrahepatic bile duct invasion,and perineural invasion are independent risk factors.A nomogram based on these factors can be used to personalize and improve treatment strategies.展开更多
Gallbladder cancer(GBC)is a rare disease with a poor prognosis.Simple cholecystectomy may be an adequate treatment only for very early disease(Tis,T1a),whereas reoperation is recommended for more advanced disease(T1b ...Gallbladder cancer(GBC)is a rare disease with a poor prognosis.Simple cholecystectomy may be an adequate treatment only for very early disease(Tis,T1a),whereas reoperation is recommended for more advanced disease(T1b and T2).Radical cholecystectomy should have two fundamental objectives:To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes.However,recent studies have shown that compared with lymph node dissection alone,liver resection does not improve survival outcomes.The oncological roles of lymphadenectomy and liver resection is distinct.Therefore,for patients with incidental GBC without liver invasion,hepatic resection is not always mandatory.展开更多
BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for ...BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.展开更多
Gallbladder cancer(GBC)is one of the commonest biliary malignancies seen in India,Argentina,and Japan.The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs.Early detection i...Gallbladder cancer(GBC)is one of the commonest biliary malignancies seen in India,Argentina,and Japan.The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs.Early detection is the only way to improve the outcome.There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC.Therefore,it is imp-ortant and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis,early diagn-osis,treatment,and prognostication.As India being one of the largest hubs for GBC in the world,it is important to know how the country has progressed on GBC.In this review,we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.展开更多
Background:Pancreaticobiliary maljunction(PBM)is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux(PBR).However,the impact of occult pancreaticobiliary reflux(OPR...Background:Pancreaticobiliary maljunction(PBM)is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux(PBR).However,the impact of occult pancreaticobiliary reflux(OPR),which is characterized by high bile amylase levels in individuals with anatomically normal pancreaticobiliary junction,on biliary diseases remains unclear.The aim of this study was to assess the correlation between OPR and biliary diseases.Methods:We enrolled 94 consecutive patients with normal pancreaticobiliary junction and primary biliary diseases confirmed by magnetic resonance cholangiopancreatography.We prospectively collected patients’bile samples and measured bile amylase levels.We investigated the incidence of OPR and the difference in bile amylase levels among these patients and assessed the correlation between high bile amylase levels(HBAL)and benign or malignant biliary diseases,as well as the OPR risk factors.Results:The incidence of OPR was 36.6%in patients with benign biliary diseases,26.7%in those with cholangiocarcinoma and 62.5%in those with gallbladder cancer.The median bile amylase level tended to be higher in patients with gallbladder cancer than in those with benign biliary diseases,but there was no significant difference(165.5 IU/L vs.23.0 IU/L,P=0.212).The prevalence of an HBAL with bile amylase levels of 1000-7500 IU/L was similar in patients with gallbladder cancer and benign biliary diseases.However,the incidence of HBAL with bile amylase levels greater than 7500 IU/L was significantly higher in patients with gallbladder cancer than in those with benign biliary diseases(37.5%vs.4.2%,P=0.012).Multivariate logistic regression analysis revealed that choledocholithiasis was an independent risk factor for OPR.Conclusions:OPR can occur in benign and malignant biliary diseases,and it may be a pathogenic factor for some benign biliary diseases and a high-risk factor for gallbladder cancer.There is a correlation between choledocholithiasis and OPR.展开更多
BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer cases.Data are conflicting on the role of IGBC diagnosis in oncological outcomes.Some studies suggest that IGBC diagnosis does not ...BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer cases.Data are conflicting on the role of IGBC diagnosis in oncological outcomes.Some studies suggest that IGBC diagnosis does not affect outcomes,while others that overall survival(OS)is longer in these cases compared to non-incidental diagnosis(NIGBC).Furthermore,some studies reported early tumour stages and histopathologic characteristics as possible confounders,while others not.AIM To investigate the role of IGBC diagnosis on patients’overall survival,especially after surgical treatment with curative intent.METHODS Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre.Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed.Survival analysis for the whole cohort,surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test.Risk analysis was performed with univariable and multivariable Cox regression analysis.RESULTS The cohort included 261 patients with gallbladder cancer.65%of cases had NIGBC and 35%had IGBC.A total of 90 patients received surgical treatment(66%of IGBC cases and 19%of NIGBC cases).NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones.OS was longer in patients with IGBC in the whole cohort(29 vs 4 mo,P<0.001),as well as in the non-surgical(14 vs 2 mo,P<0.001)and surgical subgroups(29 vs 16.5 mo,P=0.001).Disease free survival(DFS)after surgery was longer in patients with IGBC(21.5 mo vs 8.5 mo,P=0.007).N stage and resection margin status were identified as independent predictors of OS and DFS.NIGBC diagnosis was identified as an independent predictor of OS.CONCLUSION IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics.Prospective studies are required to further investigate this,including detailed pathological analysis and molecular gene expression.展开更多
Gallbladder cancer(GBC)is a rare malignancy worldwide,with 140,000 new patients each year and more than 100,000 deaths annually.The review aims to address the controversial aspects of managing GBC.Regional differences...Gallbladder cancer(GBC)is a rare malignancy worldwide,with 140,000 new patients each year and more than 100,000 deaths annually.The review aims to address the controversial aspects of managing GBC.Regional differences of the study worldwide remain pending,and comparative mutational profiles will provide more information on the pathogenesis of GBC.However,certain pathologic aspects are discussed,such as the staging of early GBC,outcome differences between T2 pathologically staged patients,and the necessity of a uni-form pathologic report.The surgical management of GBC is still under debate.The extent of liver resection,type of lymphadenectomy,and selection of patients for extended resection are aspects of the disease that require revision.Laparoscopic and robotic approaches were initially slow to develop.However,with time,they have demonstrated their value in the surgical management of GBC.The OMEGA survey,performed to analyze the management practice of surgical treatment of GBC worldwide,demonstrated differences from the recom-mended guidelines.The OMEGA study,the largest cohort study,examined the outcomes of surgical intervention in 3676 patients from 133 centers.Regarding future directions,the value of collaborative efforts between centers and regions must be emphasized to better un-derstand the different aspects of the disease and globally improve therapeutic strategies for GBC.展开更多
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major ...Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.展开更多
AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 l...AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre-and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non- recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.展开更多
AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patien...AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffi n block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays.RESULTS:The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR:0.14,95% CI:0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR:5.04,95% CI:1.43-17.8).CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs 708272 polymorphisms may be related to the risk of developing GBC in Chilean women.展开更多
BACKGROUND Surgical resection is a treatment of choice for gallbladder cancer(GBC)patients but only 10%of patients have a resectable disease at presentation.Even after surgical resection,overall survival(OS)has been p...BACKGROUND Surgical resection is a treatment of choice for gallbladder cancer(GBC)patients but only 10%of patients have a resectable disease at presentation.Even after surgical resection,overall survival(OS)has been poor due to high rates of recurrence.Combination of surgery and systemic therapy can improve outcomes in this aggressive disease.AIM To summarize our single-center experience with multimodality management of resectable GBC patients.METHODS Data of all patients undergoing surgery for suspected GBC from January 2012 to December 2018 was retrieved from a prospectively maintained electronic database.Information extracted included demographics,operative and perioperative details,histopathology,neoadjuvant/adjuvant therapy,follow-up,and recurrence.To know the factors associated with recurrence and OS,univariate and multivariate analysis was done using log rank test and cox proportional hazard analysis for categorical and continuous variables,respectively.Multivariate analysis was done using multiple regression analysis.RESULTS Of 274 patients with GBC taken up for surgical resection,172(62.7%)were female and the median age was 56 years.On exploration,102 patients were found to have a metastatic or unresectable disease(distant metastasis in 66 and locally unresectable in 34).Of 172 patients who finally underwent surgery,93(54%)underwent wedge resection followed by anatomical segment IVb/V resection in 66(38.4%)and modified extended right hepatectomy in 12(7%)patients.The postoperative mortality at 90 d was 4.6%.During a median follow-up period of 20 mo,71(41.2%)patients developed recurrence.Estimated 1-,3-,and 5-years OS rates were 86.5%,56%,and 43.5%,respectively.Estimated 1-and 3-year disease free survival(DFS)rates were 75%and 49.2%,respectively.On multivariate analysis,inferior OS was seen with pT3/T4 tumor(P=0.0001),perineural invasion(P=0.0096),and R+resection(P=0.0125).However,only pT3/T4 tumors were associated with a poor DFS(P<0.0001).CONCLUSION Multimodality treatment significantly improves the 5-year survival rate of patients with GBC up to 43%.R+resection,higher T stage,and perineural invasion adversely affect the outcome and should be considered for systemic therapy in addition to surgery to optimize the outcomes.Multimodality treatment of GBC has potential to improve the survival of GBC patients.展开更多
BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder that can mimic gallbladder carcinoma. METHODS: We present the case of a 35-year-old Hispanic male complainin...BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder that can mimic gallbladder carcinoma. METHODS: We present the case of a 35-year-old Hispanic male complaining of right upper quadrant pain and jaundice for 2 months prior to admission. He denied a history of fever, nausea/ vomiting, and weight loss. The past medical history was relevant only for diabetes. He had no previous history of jaundice or previous operations. RESULTS: CA19-9 was slightly elevated (52 U/mL). Abdominal ultrasonography showed an irregular thickening of the gallbladder wall and no gallstones were detected. CT scan also revealed an irregular thickening of the wall of the gallbladder body suggestive of malignancy. At laparotomy, the mass was adherent to the duodenum and colon, and although the frozen section biopsy was negative, the intraoperative findings were suggestive of malignancy, and the patient underwent left liver trisegmentectomy, resection of the common bile duct and Roux-en-Y hepaticojejunostomy. Pathological examination unexpectedly revealed XGC without malignancy. CONCLUSIONS: Preoperative and intraoperative differential diagnosis of XGC from gallbladder carcinoma remains a challenge when it is associated with inflammatory involvement of surrounding tissues. Since gallbladder carcinoma and XGC may coexist, radical resection is justified when malignancy cannot be completely ruled out.展开更多
This article discusses the adequate treatment of early gallbladder cancer （Tla, Tlb） and is based on published studies extending over nearly 3 decades. Ran- domized studies and meta analyses comparing different surg...This article discusses the adequate treatment of early gallbladder cancer （Tla, Tlb） and is based on published studies extending over nearly 3 decades. Ran- domized studies and meta analyses comparing different surgical treatments do not exist. The literature shows that in up to 20% of patients lymph node metastasis are found in Tlb gallbladder cancer. Due to high malignancy with early angiolymphatic spread and resistance to chemotherapy and radiation on the one hand, and the relative low operative risk of extended cholecystectomy （cholecystectomy and regional lymphadenectomy） on the other hand, we believe that this procedure is mandatory in early gallbladder cancer.展开更多
BACKGROUND: The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to define t...BACKGROUND: The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to define the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS: The numbers of CD4(+) and CD8(+) T-lymphocytes and NK cells were measured by flow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS: The numbers of CD4(+) and CD8(+) T-cells and NK cells in gallbladder cancer tissues were significantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4(+)/CD8(+) was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4(+) and CD8(+) T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were significantly different. CONCLUSIONS: Disproportionate and imbalanced distribution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4(+), CD8(+) and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.展开更多
gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the over...gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the overall 5-year survival rate for metastatic gbc patients is extremely low. BRC A1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European commission for the treatment of ovarian cancer with any BRCA1/2 mutations. the first case of BRCA1-mutated gbc patient who responded to olaparib treatment is reported here.展开更多
BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladd...BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR),its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported.This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD).METHODS:This study included 162 samples of gallbladder:94 from GBC and 68 from GSD.Expression of CCKAR was analyzed by immunohistochemistry and immunoblotting.The results were statistically correlated with disease history including age,sex,presence of gallstone,stage and differentiation.RESULTS:CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples.Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression.Interestingly,consistent results also appeared in the immunoblotting study.CONCLUSIONS:CCKAR expression was significantly increased in GBC compared to GSD.Moreover,CCKAR expression was associated with the degree of tumor differentiation,i.e.,less expression in poorly-differentiated tumors.Thus,it has future prognostic and therapeutic implications in the management of GBC.展开更多
BACKGROUND:Evidence exists of a link between chronic infection by Salmonella typhi(S.typhi) and the development of gallbladder cancer(GBC),but several studies from endemic regions contradict its role in the etiopathog...BACKGROUND:Evidence exists of a link between chronic infection by Salmonella typhi(S.typhi) and the development of gallbladder cancer(GBC),but several studies from endemic regions contradict its role in the etiopathogenesis of GBC.This study used various tools to assess the prevalence of S.typhi in patients with GBC and gallstone disease(GSD) in this region with a high incidence of GBC.METHODS:S.typhi was detected in tissue and bile by PCR and culture and in serum by the Widal test and indirect hemagglutination assay(IHA).PCR with two pairs of S.typhi specific primers(flagellin gene H1d and SOP E gene) could detect 0.6 ng of S.typhi DNA.Fifty-four patients with GBC(cases) were matched with 54 patients with GSD(controls).RESULTS:Of the 54 cases,24(44.44%) were positive on the Widal test and 12(22.22%) on IHA,compared to 13(24.07%) and 5(9.26%) respectively in the controls.Eighteen(33.33%) cases showed a positive result on PCR(tissue) and 2 on PCR(bile) vs.none in the controls.Bile culture revealed no Salmonella colonies in either cases or controls.Only 3 cases were positive for Salmonella on tissue culture compared to none in the controls.The sensitivity of PCR(tissue) relative to the Widal test,IHA,culture(bile and tissue) and PCR(bile) was 100% vs.66.67%,11.11%,and 11.11%,and the specificity was 83.33% vs.100%,100%,and 100%,respectively.CONCLUSIONS:S.typhi is significantly associated with GBC compared to GSD(33% vs.0%).PCR appears to be the most specific diagnostic tool,the gold standard for S.typhi in tissue samples.展开更多
AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer,and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgica...AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer,and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression,loss of heterozygosity (LOH),homozygous deletion and promoter hypermethylation using immunohistochemistry,microsatellite analysis,quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR,respectively. In addition,mutations were examined by direct DNA sequencing. RESULTS: Homozygous deletions of the p16 gene exon2,LOH at 9p21-22,p16 promoter hypermethylation,and loss of p16 protein expression were detected in 26.0% (13/50),56.9% (29/51),72.5% (37/51) and 62.7% (32/51),respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene,a combination LOH and promoter hypermethylation,and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene,respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION: Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion,a combination of LOH and promoter hypermethylation,and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.展开更多
We report port site and distant metastases of unsuspected gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron emission tomography （PET） in two patients. Patient 1, a 72-yearold woman was diag...We report port site and distant metastases of unsuspected gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron emission tomography （PET） in two patients. Patient 1, a 72-yearold woman was diagnosed as cholelithiasis and cholecystitis and received laparoscopic cholecystectomy. Unsuspected gallbladder cancer was discovered with histological result of well-differentiated squamous cell carcinoma of the gallbladder infiltrating the entire wall. A PET scan using F-18-fluorodeoxyglucose （FDG- PET） before radical resection revealed residual tumor in the gallbladder fossa and recurrence at port site and metastases in bilateral hilar lymph nodes. Patient 2, a 69-year-old woman underwent laparoscopic cholecystectomy more than one year ago with pathologically confirmed unsuspected adenosquamous carcinoma of stage pTlb. At 7-mo follow-up after surgery, the patient presented with nodules in the periumbilical incision. Excisional biopsy of the nodule revealed adenosquamous carcinoma. The patient was examined by FDG-PET, demonstrating increased FDG uptake in the right lobe of the liver and mediastinal lymph nodes consistent with metastatic disease. This report is followed by a discussion about the utility of FDG-PET in the gallbladder cancer.展开更多
Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with mi...Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with minimally invasive techniques,the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease.Although the treatment remains mostly surgical,newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease.We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.展开更多
基金Supported by Xiao-Ping Chen Foundation for The Development of Science and Technology of Hubei Province,No.CXPJJH122002-061.
文摘BACKGROUND Gallbladder cancer(GBC)is the most common malignant tumor of the biliary system,and is often undetected until advanced stages,making curative surgery unfeasible for many patients.Curative surgery remains the only option for long-term survival.Accurate postsurgical prognosis is crucial for effective treatment planning.tumor-node-metastasis staging,which focuses on tumor infiltration,lymph node metastasis,and distant metastasis,limits the accuracy of prognosis.Nomograms offer a more comprehensive and personalized approach by visually analyzing a broader range of prognostic factors,enhancing the precision of treatment planning for patients with GBC.AIM A retrospective study analyzed the clinical and pathological data of 93 patients who underwent radical surgery for GBC at Peking University People's Hospital from January 2015 to December 2020.Kaplan-Meier analysis was used to calculate the 1-,2-and 3-year survival rates.The log-rank test was used to evaluate factors impacting prognosis,with survival curves plotted for significant variables.Single-factor analysis revealed statistically significant differences,and multivariate Cox regression identified independent prognostic factors.A nomogram was developed and validated with receiver operating characteristic curves and calibration curves.Among 93 patients who underwent radical surgery for GBC,30 patients survived,accounting for 32.26%of the sample,with a median survival time of 38 months.The 1-year,2-year,and 3-year survival rates were 83.87%,68.82%,and 53.57%,respectively.Univariate analysis revealed that carbohydrate antigen 19-9 expre-ssion,T stage,lymph node metastasis,histological differentiation,surgical margins,and invasion of the liver,ex-trahepatic bile duct,nerves,and vessels(P≤0.001)significantly impacted patient prognosis after curative surgery.Multivariate Cox regression identified lymph node metastasis(P=0.03),histological differentiation(P<0.05),nerve invasion(P=0.036),and extrahepatic bile duct invasion(P=0.014)as independent risk factors.A nomogram model with a concordance index of 0.838 was developed.Internal validation confirmed the model's consistency in predicting the 1-year,2-year,and 3-year survival rates.CONCLUSION Lymph node metastasis,tumor differentiation,extrahepatic bile duct invasion,and perineural invasion are independent risk factors.A nomogram based on these factors can be used to personalize and improve treatment strategies.
文摘Gallbladder cancer(GBC)is a rare disease with a poor prognosis.Simple cholecystectomy may be an adequate treatment only for very early disease(Tis,T1a),whereas reoperation is recommended for more advanced disease(T1b and T2).Radical cholecystectomy should have two fundamental objectives:To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes.However,recent studies have shown that compared with lymph node dissection alone,liver resection does not improve survival outcomes.The oncological roles of lymphadenectomy and liver resection is distinct.Therefore,for patients with incidental GBC without liver invasion,hepatic resection is not always mandatory.
文摘BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.
文摘Gallbladder cancer(GBC)is one of the commonest biliary malignancies seen in India,Argentina,and Japan.The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs.Early detection is the only way to improve the outcome.There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC.Therefore,it is imp-ortant and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis,early diagn-osis,treatment,and prognostication.As India being one of the largest hubs for GBC in the world,it is important to know how the country has progressed on GBC.In this review,we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.
文摘Background:Pancreaticobiliary maljunction(PBM)is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux(PBR).However,the impact of occult pancreaticobiliary reflux(OPR),which is characterized by high bile amylase levels in individuals with anatomically normal pancreaticobiliary junction,on biliary diseases remains unclear.The aim of this study was to assess the correlation between OPR and biliary diseases.Methods:We enrolled 94 consecutive patients with normal pancreaticobiliary junction and primary biliary diseases confirmed by magnetic resonance cholangiopancreatography.We prospectively collected patients’bile samples and measured bile amylase levels.We investigated the incidence of OPR and the difference in bile amylase levels among these patients and assessed the correlation between high bile amylase levels(HBAL)and benign or malignant biliary diseases,as well as the OPR risk factors.Results:The incidence of OPR was 36.6%in patients with benign biliary diseases,26.7%in those with cholangiocarcinoma and 62.5%in those with gallbladder cancer.The median bile amylase level tended to be higher in patients with gallbladder cancer than in those with benign biliary diseases,but there was no significant difference(165.5 IU/L vs.23.0 IU/L,P=0.212).The prevalence of an HBAL with bile amylase levels of 1000-7500 IU/L was similar in patients with gallbladder cancer and benign biliary diseases.However,the incidence of HBAL with bile amylase levels greater than 7500 IU/L was significantly higher in patients with gallbladder cancer than in those with benign biliary diseases(37.5%vs.4.2%,P=0.012).Multivariate logistic regression analysis revealed that choledocholithiasis was an independent risk factor for OPR.Conclusions:OPR can occur in benign and malignant biliary diseases,and it may be a pathogenic factor for some benign biliary diseases and a high-risk factor for gallbladder cancer.There is a correlation between choledocholithiasis and OPR.
文摘BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer cases.Data are conflicting on the role of IGBC diagnosis in oncological outcomes.Some studies suggest that IGBC diagnosis does not affect outcomes,while others that overall survival(OS)is longer in these cases compared to non-incidental diagnosis(NIGBC).Furthermore,some studies reported early tumour stages and histopathologic characteristics as possible confounders,while others not.AIM To investigate the role of IGBC diagnosis on patients’overall survival,especially after surgical treatment with curative intent.METHODS Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre.Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed.Survival analysis for the whole cohort,surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test.Risk analysis was performed with univariable and multivariable Cox regression analysis.RESULTS The cohort included 261 patients with gallbladder cancer.65%of cases had NIGBC and 35%had IGBC.A total of 90 patients received surgical treatment(66%of IGBC cases and 19%of NIGBC cases).NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones.OS was longer in patients with IGBC in the whole cohort(29 vs 4 mo,P<0.001),as well as in the non-surgical(14 vs 2 mo,P<0.001)and surgical subgroups(29 vs 16.5 mo,P=0.001).Disease free survival(DFS)after surgery was longer in patients with IGBC(21.5 mo vs 8.5 mo,P=0.007).N stage and resection margin status were identified as independent predictors of OS and DFS.NIGBC diagnosis was identified as an independent predictor of OS.CONCLUSION IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics.Prospective studies are required to further investigate this,including detailed pathological analysis and molecular gene expression.
文摘Gallbladder cancer(GBC)is a rare malignancy worldwide,with 140,000 new patients each year and more than 100,000 deaths annually.The review aims to address the controversial aspects of managing GBC.Regional differences of the study worldwide remain pending,and comparative mutational profiles will provide more information on the pathogenesis of GBC.However,certain pathologic aspects are discussed,such as the staging of early GBC,outcome differences between T2 pathologically staged patients,and the necessity of a uni-form pathologic report.The surgical management of GBC is still under debate.The extent of liver resection,type of lymphadenectomy,and selection of patients for extended resection are aspects of the disease that require revision.Laparoscopic and robotic approaches were initially slow to develop.However,with time,they have demonstrated their value in the surgical management of GBC.The OMEGA survey,performed to analyze the management practice of surgical treatment of GBC worldwide,demonstrated differences from the recom-mended guidelines.The OMEGA study,the largest cohort study,examined the outcomes of surgical intervention in 3676 patients from 133 centers.Regarding future directions,the value of collaborative efforts between centers and regions must be emphasized to better un-derstand the different aspects of the disease and globally improve therapeutic strategies for GBC.
文摘Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
文摘AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre-and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non- recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
基金Supported by (in part) A Grant-in-Aid for Scientific Research (C) (2007,#19590582) from the Japanese Ministry of Education,Science,Sports and Culture
文摘AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffi n block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays.RESULTS:The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR:0.14,95% CI:0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR:5.04,95% CI:1.43-17.8).CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs 708272 polymorphisms may be related to the risk of developing GBC in Chilean women.
文摘BACKGROUND Surgical resection is a treatment of choice for gallbladder cancer(GBC)patients but only 10%of patients have a resectable disease at presentation.Even after surgical resection,overall survival(OS)has been poor due to high rates of recurrence.Combination of surgery and systemic therapy can improve outcomes in this aggressive disease.AIM To summarize our single-center experience with multimodality management of resectable GBC patients.METHODS Data of all patients undergoing surgery for suspected GBC from January 2012 to December 2018 was retrieved from a prospectively maintained electronic database.Information extracted included demographics,operative and perioperative details,histopathology,neoadjuvant/adjuvant therapy,follow-up,and recurrence.To know the factors associated with recurrence and OS,univariate and multivariate analysis was done using log rank test and cox proportional hazard analysis for categorical and continuous variables,respectively.Multivariate analysis was done using multiple regression analysis.RESULTS Of 274 patients with GBC taken up for surgical resection,172(62.7%)were female and the median age was 56 years.On exploration,102 patients were found to have a metastatic or unresectable disease(distant metastasis in 66 and locally unresectable in 34).Of 172 patients who finally underwent surgery,93(54%)underwent wedge resection followed by anatomical segment IVb/V resection in 66(38.4%)and modified extended right hepatectomy in 12(7%)patients.The postoperative mortality at 90 d was 4.6%.During a median follow-up period of 20 mo,71(41.2%)patients developed recurrence.Estimated 1-,3-,and 5-years OS rates were 86.5%,56%,and 43.5%,respectively.Estimated 1-and 3-year disease free survival(DFS)rates were 75%and 49.2%,respectively.On multivariate analysis,inferior OS was seen with pT3/T4 tumor(P=0.0001),perineural invasion(P=0.0096),and R+resection(P=0.0125).However,only pT3/T4 tumors were associated with a poor DFS(P<0.0001).CONCLUSION Multimodality treatment significantly improves the 5-year survival rate of patients with GBC up to 43%.R+resection,higher T stage,and perineural invasion adversely affect the outcome and should be considered for systemic therapy in addition to surgery to optimize the outcomes.Multimodality treatment of GBC has potential to improve the survival of GBC patients.
文摘BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder that can mimic gallbladder carcinoma. METHODS: We present the case of a 35-year-old Hispanic male complaining of right upper quadrant pain and jaundice for 2 months prior to admission. He denied a history of fever, nausea/ vomiting, and weight loss. The past medical history was relevant only for diabetes. He had no previous history of jaundice or previous operations. RESULTS: CA19-9 was slightly elevated (52 U/mL). Abdominal ultrasonography showed an irregular thickening of the gallbladder wall and no gallstones were detected. CT scan also revealed an irregular thickening of the wall of the gallbladder body suggestive of malignancy. At laparotomy, the mass was adherent to the duodenum and colon, and although the frozen section biopsy was negative, the intraoperative findings were suggestive of malignancy, and the patient underwent left liver trisegmentectomy, resection of the common bile duct and Roux-en-Y hepaticojejunostomy. Pathological examination unexpectedly revealed XGC without malignancy. CONCLUSIONS: Preoperative and intraoperative differential diagnosis of XGC from gallbladder carcinoma remains a challenge when it is associated with inflammatory involvement of surrounding tissues. Since gallbladder carcinoma and XGC may coexist, radical resection is justified when malignancy cannot be completely ruled out.
文摘This article discusses the adequate treatment of early gallbladder cancer （Tla, Tlb） and is based on published studies extending over nearly 3 decades. Ran- domized studies and meta analyses comparing different surgical treatments do not exist. The literature shows that in up to 20% of patients lymph node metastasis are found in Tlb gallbladder cancer. Due to high malignancy with early angiolymphatic spread and resistance to chemotherapy and radiation on the one hand, and the relative low operative risk of extended cholecystectomy （cholecystectomy and regional lymphadenectomy） on the other hand, we believe that this procedure is mandatory in early gallbladder cancer.
文摘BACKGROUND: The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to define the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS: The numbers of CD4(+) and CD8(+) T-lymphocytes and NK cells were measured by flow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS: The numbers of CD4(+) and CD8(+) T-cells and NK cells in gallbladder cancer tissues were significantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4(+)/CD8(+) was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4(+) and CD8(+) T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were significantly different. CONCLUSIONS: Disproportionate and imbalanced distribution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4(+), CD8(+) and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.
基金supported by International Science and Technology Cooperation Projects,No.2015DFA30650 and No.2010DFB33720Capital Special Research Project for Health Development,No.2014-2-4012Capital Research Project for the Characteristics Clinical Application,No.Z151100004015170
文摘gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the overall 5-year survival rate for metastatic gbc patients is extremely low. BRC A1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European commission for the treatment of ovarian cancer with any BRCA1/2 mutations. the first case of BRCA1-mutated gbc patient who responded to olaparib treatment is reported here.
基金supported by a grant from the Indian Council of Medical Research(ICMR Project Ref No.3/2/2/187/2009/NCD-Ⅲ)
文摘BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR),its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported.This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD).METHODS:This study included 162 samples of gallbladder:94 from GBC and 68 from GSD.Expression of CCKAR was analyzed by immunohistochemistry and immunoblotting.The results were statistically correlated with disease history including age,sex,presence of gallstone,stage and differentiation.RESULTS:CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples.Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression.Interestingly,consistent results also appeared in the immunoblotting study.CONCLUSIONS:CCKAR expression was significantly increased in GBC compared to GSD.Moreover,CCKAR expression was associated with the degree of tumor differentiation,i.e.,less expression in poorly-differentiated tumors.Thus,it has future prognostic and therapeutic implications in the management of GBC.
文摘BACKGROUND:Evidence exists of a link between chronic infection by Salmonella typhi(S.typhi) and the development of gallbladder cancer(GBC),but several studies from endemic regions contradict its role in the etiopathogenesis of GBC.This study used various tools to assess the prevalence of S.typhi in patients with GBC and gallstone disease(GSD) in this region with a high incidence of GBC.METHODS:S.typhi was detected in tissue and bile by PCR and culture and in serum by the Widal test and indirect hemagglutination assay(IHA).PCR with two pairs of S.typhi specific primers(flagellin gene H1d and SOP E gene) could detect 0.6 ng of S.typhi DNA.Fifty-four patients with GBC(cases) were matched with 54 patients with GSD(controls).RESULTS:Of the 54 cases,24(44.44%) were positive on the Widal test and 12(22.22%) on IHA,compared to 13(24.07%) and 5(9.26%) respectively in the controls.Eighteen(33.33%) cases showed a positive result on PCR(tissue) and 2 on PCR(bile) vs.none in the controls.Bile culture revealed no Salmonella colonies in either cases or controls.Only 3 cases were positive for Salmonella on tissue culture compared to none in the controls.The sensitivity of PCR(tissue) relative to the Widal test,IHA,culture(bile and tissue) and PCR(bile) was 100% vs.66.67%,11.11%,and 11.11%,and the specificity was 83.33% vs.100%,100%,and 100%,respectively.CONCLUSIONS:S.typhi is significantly associated with GBC compared to GSD(33% vs.0%).PCR appears to be the most specific diagnostic tool,the gold standard for S.typhi in tissue samples.
文摘AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer,and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression,loss of heterozygosity (LOH),homozygous deletion and promoter hypermethylation using immunohistochemistry,microsatellite analysis,quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR,respectively. In addition,mutations were examined by direct DNA sequencing. RESULTS: Homozygous deletions of the p16 gene exon2,LOH at 9p21-22,p16 promoter hypermethylation,and loss of p16 protein expression were detected in 26.0% (13/50),56.9% (29/51),72.5% (37/51) and 62.7% (32/51),respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene,a combination LOH and promoter hypermethylation,and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene,respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION: Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion,a combination of LOH and promoter hypermethylation,and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.
文摘We report port site and distant metastases of unsuspected gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron emission tomography （PET） in two patients. Patient 1, a 72-yearold woman was diagnosed as cholelithiasis and cholecystitis and received laparoscopic cholecystectomy. Unsuspected gallbladder cancer was discovered with histological result of well-differentiated squamous cell carcinoma of the gallbladder infiltrating the entire wall. A PET scan using F-18-fluorodeoxyglucose （FDG- PET） before radical resection revealed residual tumor in the gallbladder fossa and recurrence at port site and metastases in bilateral hilar lymph nodes. Patient 2, a 69-year-old woman underwent laparoscopic cholecystectomy more than one year ago with pathologically confirmed unsuspected adenosquamous carcinoma of stage pTlb. At 7-mo follow-up after surgery, the patient presented with nodules in the periumbilical incision. Excisional biopsy of the nodule revealed adenosquamous carcinoma. The patient was examined by FDG-PET, demonstrating increased FDG uptake in the right lobe of the liver and mediastinal lymph nodes consistent with metastatic disease. This report is followed by a discussion about the utility of FDG-PET in the gallbladder cancer.
文摘Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with minimally invasive techniques,the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease.Although the treatment remains mostly surgical,newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease.We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.
