Radical cholecystectomy without liver resection for peritoneal side early incidental gallbladder cancer

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.

Risk factors and survival prediction model establishment for prognosis in patients with radical resection of gallbladder cancer

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.

Gallbladder cancer:Progress in the Indian subcontinent

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.

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis

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.

Nomogram to predict overall survival after gallbladder cancer resection in China

AIM To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma(GBC) into a predictive nomogram.METHODS One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital(PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9(CA19-9) was converted into a categorical variable(cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X(GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index(C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic(ROC) curve analysis and decision curve analysis(DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, respectively.RESULTS Of these 142 GBC patients, 55(38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight(33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion(AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio(HR) = 2.9; 95% confidence interval(CI): 1.60-5.27], cCA19-9(HR = 3.2; 95%CI: 1.91-5.39), stage(HR = 1.89; 95%CI: 1.16-3.09), and resection(R)(HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combined into a survival time predictive nomogram(C-index = 0.803; 95%CI: 0.766-0.839). High prediction accuracy(adjusted C-index = 0.797) was further verified via bootstrap validation. The calibration plot demonstrated good performance of the nomogram. ROC curve analysis revealed a high sensitivity and specificity. A high net benefit was proven by DCA.CONCLUSION A nomogram has been constructed to predict the overall survival of GBC patients who underwent radical surgery from a clinical database of GBC at PUMCH.

Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer

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.

Clinical characteristics of incidental or unsuspected gallbladder cancers diagnosed during or after cholecystectomy: A systematic review and meta-analysis

AIM: To perform a systematic review of incidental or unsuspected gallbladder(GB) cancer diagnosed during or after cholecystectomy. METHODS: Data in Pub Med, EMBASE, and CochraneLibrary were reviewed and 26 publications were included in the meta-analysis. The inclusion criterion for incidental GB cancer was GB cancer diagnosed during or after cholecystectomy that was not suspected at a preoperative stage. Pooled proportions of the incidence, distribution of T stage, and revisional surgery of incidental GB cancer were analyzed.RESULTS: The final pooled population comprised 2145 patients with incidental GB cancers. Incidental GB cancers were found in 0.7% of cholecystectomies p e r f o r m e d f o r b e n i g n g a l l b l a d d e r d i s e a s e s o n preoperative diagnosis(95%CI: 0.004-0.012). Nearly 50% of the incidental GB cancers were stage T2 with a pooled proportion of 47.0%(95%CI: 0.421-0.519). T1 and T3 GB cancers were found at a similar frequency, with pooled proportions of 23.0%(95%CI: 0.178-0.291) and 25.1%(95%CI: 0.195-0.317), respectively. The pooled proportion that completed revisional surgery for curative intent was 40.9%(95%CI: 0.329-0.494). The proportion of patients with unresectable disease upon revisional surgery was 23.0%(95%CI: 0.177-0.294). CONCLUSION: A large proportion of incidental GB cancers were T2 and T3 lesions. Revisional surgery for radical cholecystectomy is warranted in T2 and more advanced cancers.

Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients

AIM To investigate the prognostic role of fibrinogen-toalbumin ratio(FAR) on patients with gallbladder cancer(Gbc) in this study.METHODS One hundred and fifty-four Gbc patients were retro-spectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve(ROc curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses.RESULTS ROc curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age(P = 0.045), jaundice(P < 0.001), differentiation(P = 0.002), resection margin status(P < 0.001), T stage(P < 0.001), TNM stage(P < 0.001), and c A199(P < 0.001) as well as albumin levels(P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio(HR): 2.343, 95% confidence interval(c I): 1.532-3.581, P < 0.001], TNM stage(P = 0.035), albumin level(HR = 0.595, 95%c I: 0.385-0.921, P = 0.020) and FAR(HR: 2.813, 95%c I: 1.765-4.484, P < 0.001) were independent prognostic factors in Gbc patients.CONCLUSION An elevated preoperative FAR was significantly correlated with unfavorable overall survival in Gbc patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with Gbc. The preoperative FAR could be used to predict the prognosis of Gbc patients, which was easily accessible, costeffective and noninvasive.

Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients

AIM To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma(GBC).METHODS The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic(ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0.RESULTS ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival(OS)(HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735(for preoperative plasma fibrinogen only) and 0.729(for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199(P < 0.001), resection margin(P < 0.001) and TNM stage(P = 0.010) were independent prognostic factors for GBC.CONCLUSION The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

MicroRNA aberrations:An emerging field for gallbladdercancer management

Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.

Systematic review on the surgical treatment for T1 gallbladder cancer

AIM:To evaluate the efficacy of simple and extended cholecystectomy for mucosa(T1a) or muscularis(T1b) gallbladder(GB) cancer. METHODS:Original studies on simple and extended cholecystectomy for T1a or T1b GB cancer were searched from MEDLINE(PubMed) ,Cochrane Library,EMBase,and CancerLit using the search terms of GB,cancer/carcinoma/tumor/neoplasm. RESULTS:Twenty-nine out of the 2312 potentially relevant publications met the eligibility criteria.Of the 1266 patients with GB cancer included in the publications,706(55.8%) and 560(44.2%) had T1a and T1b GB cancer,respectively.Simple cholecystectomy for T1a and T1b GB cancer was performed in 590(83.6%) and 375(67.0%) patients,respectively(P<0.01) .In most series,the treatment of choice was simple cholecystectomy for T1a GB cancer patients with a 5-year survival rate of 100%.Lymph node metastasis was detected in 10.9% of the T1b GB cancer patients and in 1.8%of the T1a GB cancer patients,respectively(P<0.01) .Eight patients(1.1%) with T1a GB cancer and 52 patients(9.3%) with T1b GB cancer died of recurrent GB cancer(P<0.01) . CONCLUSION:Simple cholecystectomy represents the adequate treatment of T1a GB cancer.There is no definite evidence that extended cholecystectomy is advantageous over simple cholecystectomy for T1b GB cancer.

Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update

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.

Prognostic significance of preoperative platelet count in patients with gallbladder cancer

AIM:To investigate the prognostic value of preoperative platelet count(PLT) in patients with primary gallbladder cancer(GBC).METHODS:The clinical data of 223 GBC patients after surgery was retrospectively reviewed.A receiver operating characteristic(ROC) curve was plotted to verify the optimum cutoff point for PLT.Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis.RESULTS:The ROC curve showed that the optimum cutoff point for PLT was 178 × 109/L,and the entire cohort was stratified into group A with PLT > 178 × 109/L and group B with PLT ≤ 178 × 109/L.Group A had a better survival than group B(P < 0.001).There was an obvious difference between the two groups in terms of the differentiation degree,advanced tumor stage,lymph node metastasis(P < 0.001) and pathological type(P < 0.05).The univariate analysis demonstrated that tumor location,differentiation degree,TNM stage,Nevin stage,lymph node metastasis and PLT were associated with overall survival(P < 0.001).In the multivariate analysis,PLT(P = 0.032),lymph node metastasis(P = 0.007),tumor location(P < 0.001) and TNM stage(P = 0.005) were independent prognostic factors.CONCLUSION:PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery.

Metachronous cancer of gallbladder and pancreas with pancreatobiliary maljunction

Pancreaticobiliary maljunction is a congenital anomaly in which the junction between the pancreatic duct and the common bile duct is located outside the sphincter of Oddi.It is well known that pancreaticobiliary maljunction is frequently associated with carcinoma of the biliary tract.We report a case of metachronous cancer of the gallbladder and pancreas associated with pancreaticobiliary maljunction and cystic dilatation of common bile duct in a 68-year-old Tunisian woman who underwent a cholecystectomy for acute cholecystitis.The pancreatic tumor was an adenosquamous carcinoma.Pancreaticobiliary maljunction allows for pancreatobiliary or biliopancreatic reflux which may induce biliary tract carcinoma.Few cases of multifocal cancer associated with this anomaly have been reported.The association with pancreatic carcinoma remains rare.Close attention should be given to both the biliary tract system and pancreas during the long-term follow-up of patients with pancreaticobiliary maljunction,especially after they have undergone a choledochojejunostomy.

Xanthogranulomatous cholecystitis mimicking gallbladder cancer and causing obstructive cholestasis

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.

Gallbladder cancer: Clinical and pathological approach

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

Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood,gallbladder cancer and surrounding tissue

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.

Genetic variants involved in gallstone formation and capsaicin metabolism,and the risk of gallbladder cancer in Chilean women

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.

Expression profile of cholecystokinin type-A receptor in gallbladder cancer and gallstone disease

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.

Unexpected gallbladder cancer:Surgical strategies and prognostic factors

Gallbladder cancer is the most common tumor of the biliary tract and it is associated with a poor prognosis.Unexpected gallbladder cancer is a cancer incidentally discovered,as a surprise,at the histological examination after cholecystectomy for gallstones or other indications.It is a potentially curable disease,with an intermediate or good prognosis in most cases.An adequate surgical strategy is mandatory to improve the prognosis and an adjunctive radical resection may be required depending on the depth of invasion.If the cancer discovered after cholecystectomy is a pTis or a pT1a,a second surgical procedure is not mandatory.In the other cases(pT1b,pT2 and pT3 cancer) a re-resection(4b + 5 liver segmentectomy,lymphadenectomy and port-sites excision in some cases) is required to obtain a radical excision of the tumor and an accurate disease staging.The operative specimens of re-resection should be examined by the pathologist to find any "residual" tumor.The "residual disease" is the most important prognostic factor,significantly reducing median disease-free survival and disease-specific survival.The other factors include depth of parietal invasion,metastatic nodal disease,surgical margin status,cholecystectomy for acute cholecystitis,histological differentiation,lymphatic,vascular and perineural invasion and overall TNM-stage.