Gallbladder cancer in Chile: Pathologic characteristics of survival and prognostic factors: analysis of 1,366 cases.

OBJECTIVES: To explore gallbladder cancer (GBC), the second leading cause of cancer-related death in women in Chile. METHODS: Analysis of macroscopic and microscopic variables, morphometry, and survival in 1,366 patients with GBC. RESULTS: Patients comprised 1,138 women and 228 men; diagnoses included 213 (15.6%) cases of mucosal carcinoma, 132 (9.7%) cases of muscular carcinoma, 316 (23.1%) cases of subserosal carcinoma, 382 (28.0%) cases of serosal carcinoma, and 323 (23.6%) cases beyond the serosa. Women older than 55 years with a gallbladder length greater than 9.5 cm had a five-times-greater relative risk of cancer. Those with a gallbladder wall thickness less than 7 mm had a better 5-year survival rate than those with a gallbladder wall thickness greater than 10 mm (P = .0001). Patients who had cholesterolosis of the gallbladder had 9.2 times less probability of having cancer. The infiltration level of the gallbladder wall was the most important independent prognostic factor (P < .001), followed by differentiation and lymphatic involvement (P < .001 and P = .05, respectively). Vascular infiltration had a mortality rate of 100%. CONCLUSIONS: Morphologic features are strongly associated with the prognosis of GBC and must be taken into consideration when supplementary treatment is recommended.

[Association between cholesterolosis and gallbladder cancer]. / Colesterolosis y cáncer de la vesícula biliar.

BACKGROUND: Cholesterolosis is frequently observed in cholecystectomies performed for lithiasis or chronic cholecystitis. AIM: To determine the degree of association between cholesterolosis and gallbladder cancer. MATERIAL AND METHODS: In a prospective study of gallbladder cancer, all gallbladders obtained during cholecystectomies were processed for pathological study, following a special protocol. As part of this study, 23,304 surgical samples obtained between 1993 and 2002 were studied, looking for a relationship between cholesterolosis and chronic cholecystitis, adenomas, dysplasia and gallbladder cancer. RESULTS: Seventy nine percent of patients were women. Cholesterolosis was observed in 3123 cases (13.4%). Cholesterolosis was more common in women (14.2%) than in men (10.2%9) (p < 0.001). In the same period, 29 patients were diagnosed with adenomas (0.12%), 179 cases with dysplasia not associated with gallbladder cancer (0.8%) and 739 gallbladder cancer (3.2%). The frequency of cholesterolosis was 13.8% in chronic cholecystitis, 13.7% in adenomas, 12.1% in dysplasias and 1.35% in patients with gallbladder cancer (p < 0.01). Of the thirteen cases with gallbladder cancer and cholesterolosis, 10 were early gallbladder carcinomas. Patients with cholesterolosis were 9.2 times less likely td have cancer than those who did not have cholesterolosis. CONCLUSIONS: Cholesterolosis has a strong negative association with gallbladder cancer.

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.

[Inactivation of CDKN2A gene (p16) in gallbladder carcinoma]. / Inactivación del gen CDKN2A (p16) en cáncer de la vesícula biliar.

BACKGROUND: The CDKN2A gene encodes a cyclin dependent kinase inhibitor, p16, which promotes cell cycle arrest. Methylation of the promoter region transcriptionally inactivates the gene. AIM: To study the relationship between methylation status of the prometer region of p16 gene, the immunohistochemical expression of p16 and clinical and morphological features of gallbladder carcinoma. MATERIAL AND METHODS: We analyzed the methylation status of the promoter region of the CDKN2A gene in gallbladder adenocarcinomas using methylation specific PCR (MSP). We also used microsatellite markers near the CDKN2A gene to detect allelic imbalance (AI) and examined the tumors by immunohistochemistry (IHC) for p16 expression. RESULTS: Of 38 gallbladder adenocarcinomas analyzed by IHC, 11 cases (29%) were negative for p16 protein. Nine (24%) had methylation of the promoter region of the CDKN2A gene. Twenty nine cases were negative for methylation, but four (14%) of these 29 exhibited AI at one or more of the microsatellite markers. CDKN2A promoter methylation was not associated with microsatellite instability (MSI-H). CONCLUSIONS: The inactivation of CDKN2A by methylation and/or deletion might play an important role in gallbladder carcinogenesis.

[Subserous gallbladder carcinoma: expression of cadherine-catenine complex]. / Carcinoma subseroso de la vesícula biliar: expresión del complejo caderina-catenina.

BACKGROUND: Subserous gallbladder carcinoma is difficult to diagnose and treat. There are no tissue markers with prognostic value in this type of tumor. AIM: To study the immunohistochemical expression of E-cadherin alpha and beta catenin in subserous gallbladder carcinoma. PATIENTS AND METHODS: One hundred seventeen subjects (103 women and 14 men aged 62 and 69 years as a mean, respectively), were studied. Thirty five gallbladder samples without evidence of cancer were used as controls. Expression of markers was studied with standard immunohistochemical techniques for formalin fixed and paraffin embedded tissue. RESULTS: Ninety seven percent of tumors were adenocarcinoma. A lower or absent expression of E-cadherin, alpha catenin and beta catenin was observed in 26, 33 and 29% of tumors, respectively. Actuarial five years survival was 37%. No association between macroscopic features of the tumor and survival was observed. Well differentiated tumors had a 73% survival, whereas less differentiated tumors had a 30% survival. Tumors with a normal expression of the markers had a slightly better survival, although not significant (p = 0.06). CONCLUSIONS: Approximately 30% of subserous gallbladder carcinoma have an abnormal expression of E-cadherin, alpha catenin and beta catenin. This abnormal expression has no relationship with prognosis and is probably secondary to the aberrant genic expression of the tumor.

Formas de invasión tumoral en el cáncer de la vesícula biliar: importancia del diagnóstico de la infiltración tumoral vascular sanguínea / Diagnosis of vascular invasion using victoria blue stain in gallbladder carcinoma

Background: The infiltration of venous blood vessels in gallbladder carcinoma and its importance as a Prognostic factor has not been well studied. Victoria blue stain has been used to identify vascular involvement in gastric and thyroidal carcinomas. Aim: To assess blood vessel infiltration using Victoria blue stain in gallbladder carcinomas. Material and methods: One hundred forty eight samples of gallbladder carcinoma, coming from 24 men and 123 women aged 60.4ñ12.2 years old, were studied. They were stained with Victoria blue stain to quantify blood vessel invasion. Results: Twenty nine percent of tumors had blood vessel infiltration, 61 percent had lymph vessel and 20 percent had perineural infiltration. Lymph vessel or perineural involvement was found in 81por ciento and 31 percent of those tumors with blood vessel infiltration, respectively. Perineural infiltration was associated with lymph or vascular involment in 93 and 40 percent of tumors, respectively. None of the early carcinomas had blood vessel infiltration, whereas 33 percent of advanced tumors had this type of infiltration (p< 0.001). No differences in vascular infiltration were observed according to the differentiation of the tumor Conclusions: Blood vessel infiltration was observed only in advanced gallbladder carcinomas and was tightly related to the degree of gallbladder wall infiltration. The presence of perineural infiltration was the best ma rker of 1ymph or blood vessel infiltration