Incidental gall bladder cancers: Are they truly incidental?

AIM: To seek and analyze features suggestive of gallbladder cancer (GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC (IGBC).METHODS: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period (2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect.RESULTS: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, difficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42 (53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis.CONCLUSION: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality.     

Gallbladder carcinoma incidentally encountered during laparoscopic cholecystectomy: how to deal with it

Gallbladder cancer (GBC), characterised by rapid progression and a poor prognosis with a high mortality rate, is a complex disease to treat. Incidental gallbladder carcinoma (IGBC) is defined as carcinoma of the gallbladder suspected for the first time during cholecystectomy or accidentally found on histological examination of the gallbladder. With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC) and difficulties in diagnosing GBC preoperatively, the number of cases of IGBC during and after LC has increased. However, management of IGBC is a difficult issue in the absence of established guidelines. Problems associated with IGBC related to LC are the decisions of whether, when and how to perform additional surgery. Controversy remains regarding the effectiveness of additional resection in different stages of GBC. This review gives an overview of IGBC related to LC, and further discusses the preoperative, intraoperative and postoperative diagnosis and management of IGBC during LC.     

Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma

BACKGROUND: The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma. METHODS: The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed. RESULTS: A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m(2) was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1-15 treatment cycles. Nine patients (14%)-11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC-had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5-15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4-8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4-15.4 months) for patients with GBC. The most common toxicity was hand-foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers. CONCLUSIONS: Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single-agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA.     

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m(-2), day 1) plus capecitabine (1000 mg m(-2) b.i.d., days 1-14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0-15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3-11.7; ECC: 16.8 months; 95% CI, 12.7-20.5), and 5.2 months (95% CI, 0.6-9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3-4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.     

CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.     

Management of carcinoma of the gallbladder: a single-institution experience in 16 years

BACKGROUND: Radical surgery is the only curative treatment for carcinoma of gallbladder. This study aimed to evaluate the outcome of patients with carcinoma of gallbladder managed in a single institution over 16 years. METHODS: From April 1988 to November 2003, 86 patients (29 males, 57 females) were diagnosed to have carcinoma of gallbladder. Tumor staging, treatment modalities and clinical outcome of these patients were evaluated. Thirty-two patients (37%) had early stage (TNM stage I or II) disease whereas 54 patients (63%) had advanced stage (TNM stage III or IV) disease. Curative treatment by surgical resection was performed in 23 patients (27%). RESULTS: Overall survival was significantly better in patients with curative treatment (1-year: 85%; 2-year: 63%; 3-year: 55%) than those with palliative treatment (1-year: 11%; 2-year: 3%; 3-year: 0%; P < 0.01). Using Cox regression model, curative treatment was the only independent prognostic factor affecting overall survival of patients with carcinoma of gallbladder. A significantly better survival was associated with curative treatment compared with palliative treatment in patients with incidental gallbladder cancer. The median survival was 33.9 months for the curative treatment group versus 3 months for the palliative treatment group (P = 0.0001). CONCLUSION: Favorable survival outcome can be achieved in patients with carcinoma of gallbladder after curative resection.     

晚期原发性胆囊癌的化疗

目的:回顾性分析比较联合化疗及最佳支持治疗对晚期原发性胆囊癌的临床受益反应率及生存期。方法:将39例晚期原发性胆囊癌的患者非随机地分成3组,其中FAP组12例;GFO组8例;BSC组19例。化疗组每3～4周重复1次,治疗2周期后进行疗效评价,采用KaplanMeier法分析患者生存期,Logrank法进行检验。结果:FAP组的客观有效率16.7%(2/12),GFO组为25.0%(2/8),两组相比无显著性差异(P>0.05)。临床受益反应(CBR)率三组分别为25.0%、37.5%和26.3%;如将FAP组和GFO组合并成化疗组,化疗组与BSC组无显著性差异(P>0.05)。化疗组和BSC组的平均生存时间分别为6.7月和5.2月,两组用Logrank检验后无显著性差异(P>0.05)。结论:对于晚期原发性胆囊癌患者,应用FAP和GFO方案化疗并不优于最佳支持治疗。     

Clinicopathological Study of Gall Bladder Carcinoma with Special Reference to Gallstones: Our 8-year Experience from Eastern India

Gallbladder carcinoma (GBC) is the commonest cancer of the biliary tree and the most frequent cause of deathfrom biliary malignancies. The incidence of GBC shows prominent geographic, age, race, and gender-relateddifferences and is 4-7 times higher in patients with gallstones. This prompted us to study the clinicopathologicalaspects of the disease and the incidence of gallstones in gallbladder carcinoma patients, in this part of India. Inthis, combined retrospective (Jan 2004-March 2010) and prospective study (April 2010-Dec 2011) of eight years,198 patients of gallbladder carcinoma (50 males and 148 females), (range 28-82 years; mean 55 years) were studied.Most of the patients were poor and presented with abdominal pain and mass, with abnormal lab parameters.Gallstones were present in 86% of patients. Surgical exploration was performed in 130, with gallbladder resectionin 60 (including 7 incidental GBC). Adenocarcinoma (87.7%) was the commonest histological type. The studyindicates that GBC is common in our scenario. It is a disease of elderly females, has a strong association withgallstones and every cholecystectomy specimen should be examined histopathologically.     

Carcinoma of the gallbladder: Patterns of presentation,prognostic factors and survival rate. An 11-year single centre experience

Background

This report examines the patterns of presentation, prognostic factors and survival rate of all patients with gallbladder cancer (GBC) evaluated at our tertiary academic hospital over an 11-year period.

Methods

A retrospective review of a prospectively collected database of all patients with GBC presenting between January 1998 and December 2008 was performed.

Results

102 GBC-patients were included: 69 women and 33 men (median age: 65,5 years). Forty-five patients presented with incidental gallbladder cancer (IGC) and 57 with nonincidental cancer (NIGC). Curative surgery rate was 84.4% for IGC and 29.8% for NIGC (p < 0.001). Five-year actuarial survival rate was 63.2% for patients with curative intent surgery and 0% for patients with palliative approach. Patients with IGC had a longer survival rate compared to patients with NIGC (median: 25.8 vs. 4.4 months, p < 0.0001). For patients with radical resection (42 patients), there was no difference between IGC and NIGC. The incidence of liver involvement was respectively 0%, 20.8%, 58.3%, 100% for pT1, pT2, pT3 and pT4 tumors. Univariate analysis showed that survival rate was significantly affected by perineural invasion, T, N and M-stage, R0 resection, liver involvement, CA-19.9. In multivariate analysis, liver involvement was the only independent factor.

Conclusions

Majority of patients with a potentially curable disease had IGC. Almost 80% of patients with NIGC presented with unresectable disease. For patients who underwent resection with curative intent, actuarial 5-year survival was 63.2%. Liver involvement was the only independent prognostic factor. All patients with IGC and a pT2 or more advanced T stage should undergo a second radical resection.     

Evaluation of two modified ECF regimens in the treatment of advanced gallbladder cancer

Gallbladder cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy for it has not been established yet. The aim of this study is to evaluate efficacy and safety of two modified ECF regimens in advanced gallbladder cancer patients. Clinical data of 38 patients with advanced gallbladder cancer treated with modified ECF regimen were reviewed retrospectively. Of them, 21 patients received an epirubicin, cisplatin, and 5-FU/LV combination therapy. Seventeen patients received a chemotherapy of epirubicin, cisplatin, and capecitabine. Partial response was achieved in fourteen (36.84%) patients with a median duration of 5 months (range, 3-13 months), while stable disease was achieved in eight patients (21.05%). The median time to progression was 4.0 months (95% CI, 3.62-4.58 months). And the median overall survival was 9.8 months (95% CI, 7.26-12.34 months). Responders demonstrated better survival than non-responders (median survival time: 16 vs. 6.9 months, P = 0.008). The median survival time for epirubicin-, cisplatin- and capecitabine-treated patients was 9.2 versus 8.9 months for epirubicin-, cisplatin- and 5-FU/LV-treated patients. There was no statistical difference between both treatment groups in terms of survival time (P = 0.769). Regimen-related toxicity resulted in at least one treatment delay or dosage reduction in 63.2 and 34.2% patients, respectively. There were no chemotherapy-related deaths during the study. Modified ECF regimen with epirubicin, cisplatin and 5-FU/LV or substituting capecitabine for 5-FU/LV is still a potentially effective therapeutic chemotherapy for patients with advanced gallbladder cancer, and toxicity was manageable. There was no remarkable difference in efficacy between the two regimens.     

Positive cystic duct margin at index cholecystectomy in incidental gallbladder cancer is an important negative prognosticator

BackgroundPrognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER).MethodsThis retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed.ResultsThe study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; p = 0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04–2.78; p = 0.034).ConclusionsA positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes.     

Primary carcinoma of gallbladder in Yazd, Iran: A 14-year study (1992–2006)

Aim: To investigate the clinico‐pathological profile and stage of disease at presentation of patients with carcinoma of the gallbladder diagnosed during 1992–2006 in Iran. Methods: During this study period 34 consecutive patients with gallbladder carcinoma were identified using a pathology‐based tumor database. The data extracted for each study patient included their gender, age at diagnosis, signs and symptoms, presence of gallstones and histopathological pattern of the gallbladder carcinoma and the UICC/AJCC TNM staging system was used for labeling the stages of the disease. Results: The median age of the 34 patients studied was 69.50 with most between 61 and 70 years of age. The age range of the men was between 53 and 80 years with a median age of 71.50 years and that of the women was between 33 and 79 years with a median age of 68.50 years. The most common symptom was pain in the right hypochondrium. More women had gallstones (15/34) than men (3/10). Adenocarcinoma was the most common histopathological type (91.18%) with the commonest subtype being papillary (47.06%). Eighteen patients had stage IB and stage IIA (52.94%) carcinomas whereas stages IIB and III were observed in six (17.6%) and seven cases (20.6%), respectively. Only three cases (8.82%) were seen in stage IV. The follow up of gall bladder carcinoma (GBC) patients in this study ranged from 6 to 60 months. However, there was a progressive reduction of patients attending follow‐up oncology clinic, particularly by those who had stages III and IV of the disease. Conclusion: Most patients (52.94%) presented with early disease (stage IB and IIA) which carries a good prognosis. Early detection of GBC and a national consensus for the evidence‐based management of GBC in Iran should be the major components of a strategy aimed at improving therapeutic outcome.     

Do TNFA -308 G/A and IL6 -174 G/C gene polymorphisms modulate risk of gallbladder cancer in the north Indian population?

OBJECTIVES: Gallbladder carcinoma (GBC) is highly aggressive neoplasm which arises in the background of gall stones and inflammation. GBC affects women 2-3 times more frequently than men. Pro-inflammatory TNFA and IL6 gene polymorphism has been associated with various inflammatory diseases. The aim of this study was to investigate whether TNFA -308 (G/A) and IL6 -174 G/C polymorphisms within flanking region of the genes are associated with GBC susceptibility. METHODS: The promoter polymorphisms were genotyped using PCR-RFLP in 200 healthy subjects and 124 GBC patients. RESULTS: Frequency distribution of TNFA -308 (G/A) and IL6 -174 G/C were not significantly different in GBC patients in comparison to healthy controls. However, frequency of TNFA -308 (G/A) polymorphism in female GBC patients without gallstone were significantly different (p-value= 0.006) when compared to healthy female subjects (OR=3.054; 95% CI=1.39-6.72). CONCLUSION: These results suggest that TNFA -308 (G/A) polymorphism may influence the susceptibility of female gender gallbladder cancer in absence of gallstones while IL6 -174 G/C polymorphism does not seem to be playing significant role in the susceptibility to gallbladder cancer.     

Adjuvant radiotherapy improves long-term survival after resection for gallbladder cancer A population-based cohort study

BackgroundData supporting routine use of adjuvant radiotherapy (RT) compared to without RT (noRT) for gallbladder cancer (GBC) is unclear. This study aimed to determine whether RT improves long-term survival following resection for GBC.MethodsPatients receiving resection for GBC followed by RT from 2004 to 2016 were identified from the National Cancer Database (NCDB). Patients with survival <6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of RT on overall survival.ResultsOf 7514 (77%) noRT and 2261 (23%) RT, 2067 noRT and 2067 RT patients remained after PSM. After matching, RT was associated with improved survival (median: 26.2 vs 21.5 months, p < 0.001), which remained after multivariable adjustment (HR: 0.82, CI_95%: 0.76–0.89, p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (HR: 0.84, CI_95%: 0.77–0.93), N1 (HR: 0.77, CI_95%: 0.68–0.88), N2/N3 (HR: 0.56, CI_95%: 0.35–0.91), margin status: R0 (HR: 0.85, CI_95%: 0.78–0.93), R1 (HR: 0.78, CI_95%: 0.68–0.88) and use of adjuvant chemotherapy (AC) (HR: 0.67, CI_95%: 0.57–0.79). Benefit with RT were also seen in patients with T2 - T4 disease and in patients undergoing simple and extended cholecystectomy.ConclusionRT following resection was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings may suggest addition of RT into multimodality therapy for GBC.     

Evaluation of two modified ECF regimens in the treatment of advanced gallbladder cancer

Gallbladder cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy for it has not been established yet. The aim of this study is to evaluate efficacy and safety of two modified ECF regimens in advanced gallbladder cancer patients. Clinical data of 38 patients with advanced gallbladder cancer treated with modified ECF regimen were reviewed retrospectively. Of them, 21 patients received an epirubicin, cisplatin, and 5-FU/LV combination therapy. Seventeen patients received a chemotherapy of epirubicin, cisplatin, and capecitabine. Partial response was achieved in fourteen (36.84%) patients with a median duration of 5 months (range, 3–13 months), while stable disease was achieved in eight patients (21.05%). The median time to progression was 4.0 months (95% CI, 3.62–4.58 months). And the median overall survival was 9.8 months (95% CI, 7.26–12.34 months). Responders demonstrated better survival than non-responders (median survival time: 16 vs. 6.9 months, P = 0.008). The median survival time for epirubicin-, cisplatin- and capecitabine-treated patients was 9.2 versus 8.9 months for epirubicin-, cisplatin- and 5-FU/LV-treated patients. There was no statistical difference between both treatment groups in terms of survival time (P = 0.769). Regimen-related toxicity resulted in at least one treatment delay or dosage reduction in 63.2 and 34.2% patients, respectively. There were no chemotherapy-related deaths during the study. Modified ECF regimen with epirubicin, cisplatin and 5-FU/LV or substituting capecitabine for 5-FU/LV is still a potentially effective therapeutic chemotherapy for patients with advanced gallbladder cancer, and toxicity was manageable. There was no remarkable difference in efficacy between the two regimens.

     

Gallstones and gallbladder cancer-volume and weight of gallstones are associated with gallbladder cancer: a case-control study

BACKGROUND: Gallstones are considered the most important risk factor for gallbladder cancer. AIM: To identify differences in the number, weight, volume, and density of gallstones associated with chronic cholecystitis (CC), gallbladder dysplasia (GD), and gallbladder cancer (GBC). METHODS: A total of 125 cases were selected, of which 93 had gallstones associated with GBC and 31 had gallstones associated with GD. The controls were those with CC, matched by sex and age. The number, weight, volume, and density of these gallstones were examined in order to determine differences and relative cancer risk. RESULTS: Number: Multiple gallstones were present in over 76% of cases (GBC and GD) and controls (P = ns). The average number of multiple stones was 21 in GBC versus 14 in controls (P < 0.01). Weight: The average weight of the gallstones was 9.6 g in GBC versus 6.0 g in controls (P = 0.0004). The average weight in multiple stones over 10 g had strong association with GBC (P = 0.0006). Volume: The average volume was 11.7 and 6.48 ml in GBC and controls (P = 0.0002). Average volumes of 6, 8, and 10 ml had a relative cancer risk of 5, 7, and 11 times, respectively. Size: No differences were shown between GBC, GD, and controls. CONCLUSIONS: The volume of gallstones associated with other risk factors of GBC may be helpful in prioritizing cholecystectomies in symptomatic patients.     

Slow acetylator genotype of N-acetyl transferase2 (NAT2) is associated with increased susceptibility to gallbladder cancer: the cancer risk not modulated by gallstone disease

This study comprised 124 consecutive cases of proven GBC and 147 healthy controls. NAT2 polymorphisms were carried out using PCR-RFLP method. The NAT2 slow acetylator genotype was significantly associated with risk of GBC (OR 3.4, 95% CI =1.9-5.7 p = 0.000007). The NAT2 2*6 and 2*7 allele frequencies were higher in GBC and conferred significant risk of cancer (OR 1.9, 95% Cl = 1.2-2.9, p= 0.006; OR, 2.9, 95% Cl = 1.6-5.2, p = 0.0001). The haplotypes 2, 1, 1 and 1, 2, 1 were significantly higher (OR 3.7 95% Cl 2.1-7.0, p = 0.00001; OR 1.8 95% Cl =1.1-2.8, p = 0.008) in GBC. The risk of slow acetylator phenotype in GBC patients with or without gallstones was similar. These results suggest that NAT2 slow acetylator phenotype influences the susceptibility of gallbladder cancer and the risk is not modulated by gallstone disease.     

Low Expression of MicroRNA335-5p Is Associated with Malignant Behavior of Gallbladder Cancer: A Clinicopathological Study

Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cellular processes during cancerprogression, identified to be involved in tumorgenesis of several cancers including cancers of digestive system. Howeverits role in gallbladder inflammatory disease (GID) and gallbladder cancer (GBC) has not been well documented.The present study was aimed to investigate the clinical significance of hsa-miRNA-335-5p (miR-335) in GBC andGID. Subjects and Methods: This prospective case control study, conducted from July 1, 2014 to December 1, 2017in Era’s Lucknow Medical College & Hospital, India, evaluated miR-335 expression by real-time polymerase chainreaction. Hundred tissue samples GID (control; n=50) and GBC (case; n=50) were studied. Relative quantification oftarget miR-335 expression was examined using the comparative cycle threshold method. Their expression was correlatedwith different clinicopathological parameters. Fishers’ exact test, Student’s t-test, and Chi-square test were used asappropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rate.Two sided PGBC lesions when compared with GID lesions (P<0.001). The low expression level of miR-335 was correlated withhistological grade (P=0.007), clinical stage (P<0.001), lymph node metastasis (P<0.001) and liver metastasis (P=0.016).Reduced expression of miRNA-335 was associated with a shorter median overall survival (7 months vs. 25 months)in GBC patients (P<0.001). Conclusions: Down regulation of miR-335 is associated with the severity of the diseaseand thus indicate that miR-335 expression may serve as prognostic marker for GBC.     

Gallbladder cancer: Incidence and survival in a high‐risk area of Chile

We assessed population incidence rates 1998–2002 and 5‐year survival rates of 317 primary gallbladder cancer (GBC) entered in the population‐based cancer registry in Valdivia. We analyzed GBC incidence (Poisson regression) and GBC survival (Cox regression). Cases were identified by histology (69.4%), clinical work‐up (21.8%), or death certificate only (8.8%). Main symptoms were abdominal pain (82.8%), jaundice (53.6%) nausea (42.6%), and weight loss (38.2%); at diagnosis, 64% had Stage TNM IV. In the period, 4% of histopathological studies from presumptively benign cholecystectomies presented GBC. GBC cases were mainly females (76.0%), urban residents (70.3%), Hispanic (83.7%) of low schooling <4 years (64.0%). GBC standardized incidence rate per 100,000 (SIR) were all 17.5 (95%CI: 15.5–19.4), women 24.3, and men 8.6 (p < 0.00001); Mapuche 25.0, Hispanic 16.2 (p = 0.09). The highest SIRs were in Mapuche (269.2) and Hispanic women (199.6) with <4 years of schooling. Lowest SIRs were among Hispanic men (19.8) and women (21.9) with >8 years of schooling. Low schooling, female and urban residence were independent risk factors. By December 31, 2007, 6 (1.9%) cases were living, 280 (88.3%) died from GBC, 32 (10.1%) were lost of follow‐up. Kaplan Meier Global 5‐year survival was: 10.3%, 85% at stage I and 1.9% at stage IV; median survival: 3.4 months. Independent poor prognostic factors were TNM IV, jaundice and nonincidental diagnoses. Our results suggest that women of Mapuche ancestry with low schooling (>50 years) are at the highest risk of presenting and dying from GBC and should be the target for early detection programs.