Iván Roa E

Carcinoma incipiente de la vesícula biliar. Estudio clínico-patólogico y pronóstico de 196 casos

Background: There is little information about the behavior of early gallbladder carcinoma. Aim: To report the clinical and pathological features of 196 patients with early gallbladder carcinoma. Material and methods: All patients with gallbladder cancer diagnosed between 1988 and 1997 were reviewed. In 703 of 829 patients, there was information about clinical features and follow up, and were included in this study. All gallbladders were subjected to a complete mapping. When neoplastic cells involved only the mucosa or muscular layer, the tumors were considered as early. Results: One hundred ninety six patients had an early carcinoma (161 women, aged 57.5 years and 35 male, aged 63.4 years). One hundred twenty eight tumors were located in the mucosa and 68 in the muscular layer. Patients with tumors involving the mucosa were younger than those with tumors involving the muscular layer. All tumors were adenocarcinomas, 66% were well differentiated and 32% moderately differentiated. Tumors were not visible macroscopically in 132 cases. Five and 10 years survival was 92%. Subjects of less than 40 years old had a 100% survival at 5 years. A hepatic and lymph node resection was done in 12 patients with tumors infiltrating the muscular layer but in only one, the tumor infiltrated the liver. No difference in survival was observed when a simple cholecystectomy or radical surgery was done. Conclusions: Nearly 25% of gallbladder carcinomas can be classified as early and its diagnosis requires a directed study

Pólipos y adenomas de la vesícula biliar: consideraciones clínico-patológicas

: In a period of 10 years, 21.412 gall-bladders were processed. Among these, 884 carcinomas were diagnosed and in 219 cases (1%)a polyp was found. One hundred and eighty three patients were females (mean age 49.3 years)and 36 males (mean age 53.4 years). The preoperative diagnosis of gallbladder polyp was doneonly in 26 cases (12%). Eighty five percent of polyps were non-neoplastic (metaplastic in 32%,cholesterol in 29%, hyperplastic in 22% and inflammatory in 2%). The remaining 15% wereadenomas. Seventy five percent of non-neoplastic polyps were located in the proximal half of thegallbladder and 88% of adenomas in the distal half. Ninety five percent of non-neoplastic pol-yps measured less than 10 mm. Among adenomas, 47% measured less than 5 mm and 28%more than 10 mm. Smaller polyps were of cholesterol and larger polyps were adenomas. Eightadenomas were associated with an adenocarcinoma, two had less than 5 mm lenght. Mean ageof patients with adenomas associated to cancer was higher than patients with pure adenomas(64.6 and 44.3 years respectively, p >0.001).

Tipificación del virus papiloma humano (VPH) en lesiones preneoplásicas y carcinoma del cuello uterino en mujeres de la IX Región-Chile

: Detection of HPV was 40% in cases without histologicallesion, 88% in low grade lesions, 89% in high grade lesions (HGL) and 93.5% in invasive carcino-ma. Of all HPV positive cases, 89.5% were classified as high risk and only a 4.9% of HPV caseswere of low risk type. Six percent of cases had multiple infections. Distribution of viral genotypesaccording to RFLP was: HPV33 (25.3%), 16 (18.7%), 52 (13.3%), 31 (12%), 35 (6.6%), 18(2.7%).

Quimiorradioterapia de neoadyuvancia en cáncer de vesÍcula biliar

Twenty three gallbladder cancer patients were prospectively treated between June1993 and September 1999 in the Temuco Regional Hospital. Eighteen (82%) patients had subse-rosal infiltration, while three (13%) had serosal and two (9%) adipose tissue infiltration. Che-motherapy was done with 5-fluorouracil in continuous infusion during 5 days at day 1 and 28of treatment. Radiotherapy consisted in a total dose of 4500 cGy, divided in 25 sessions. Pa-tients’ survival was compared with a series of 19 patients not subjected to chemoradiation, for-merly treated at the institution.

Estudio comparativo de detección del virus papiloma humano (VPH) en muestras citológicas y biopsias de cuello uterino

Background: The DNA quality for the detection and typification of Human Papilloma Virus (HPV) varies according to the type of sample in which it is studied. This may affect the sensitivity and specificity of the method employed. Aim: To study the yield and specificity of HPV detection and typification in uterine cervical samples obtained by cervical brushing fresh frozen and formalin fixed tissue. Material and methods: Cytological, fresh frozen and fixed tissue samples from 44 patients (nine with low grade lesions and 35 with high grade lesions) were studied. Nested polymerase chain reaction for genes E6/E7 was used to typify HPV groups as low risk or high risk. Results: Of all the cytological samples obtained by brushing 84% of fixed samples and 43% of fresh frozen samples were positive for HPV. The yields were significantly different when comparing brushing with fixed tissue or fresh frozen tissue and fixed tissue with fresh frozen tissue (p <0.05). The frequency of high risk HPV fluctuated from 41% in fresh frozen tissue to 98% in cytological samples. Low risk HPV was detected in 16% of fresh frozen tissue and 68% of cytological samples. A mixed infection was detected in 66%, 41% and 14% of cytological, fresh frozen and fixed tissue samples respectively. Conclusions: Cytological samples obtained by brushing had the highest yield for the detection of cervical infection with HPV (Rev Med Chile 2005; 133: 639-44). (Key Words: Cytological techniques; Cytopathology; Papillomavirus, human)

Elementos morfológicos pronósticos en el cáncer de la vesícula biliar

Background: The exact survival rates and prognostic factors of gallbladder cancer are still incompletely known. Aim: To report the actuarial survival of patients with gallbladder cancer. Material and methods: Six hundred thirty seven women, aged 59 years old as a mean and 108 men, aged 64 years old as a mean, with gallbladder cancer are reported. Patients were followed for up to 150 months. Results: Two hundred twenty four patients had an early and 521 had an advanced carcinoma. Overall survival was 38% at ten years. Sex or ethnic origin did not influence survival. Early tumors had a 92% survival at 10 years whereas the survival of advanced tumors was 16% at 5 years. Subserous tumors had a 5 years survival of 32% whereas serous tumors had a 5 years survival of 11%. Well-differentiated advanced tumors had a significantly better survival than moderately or poorly differentiated tumors. Vascular or lymphatic infiltration was also associated to a lower survival. All patients with advanced tumors and vascular infiltration died before 5 years. Conclusions: Tumor infiltration and differentiation degree were the most important prognostic independent factors in gallbladder cancer (Rev Med Chile 2002; 130: 387-395)

Patrón de metilación génico en el cáncer de mama

: We found methylation inat least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. Thefrequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHIT were41.4%, 11.4%, 52.9%, 70% y 42.9%, respectively. We found a relationship between CDKN2A me-thylation and better survival (p=0.002). CDH1 methylation and poor histological differentiation(p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=0.03), APC methylation and larg-er tumor size (p <0.05), FHIT methylation and lack of estrogen receptor IHC expression (p <0.05).

Mutación del gen p53 en el cáncer de la vesícula biliar

33 formalin fixed paraffin embedded samples of gallbladdercarcinoma (30 women, age range 32-86 years) were selected. Pancreatic cancer tissue with K-ras mutations was used as control. DNA was extracted from the histological section by mean ofmicrodissection and K-ras mutations in codon 12 were detected by polymerase chain reactionand restriction fragment length polymorphism (RFLP), using previously reported technique.

Estudio bacteriológico de la bilis vesicular en un área de alto riesgo de cáncer vesicular

BACKGROUND: Gallbladder cancer is frequent in Chile and there is sparse information about the association between this type of cancer and the presence of bacteria in the gallbladder bile. AIM: To determine the presence of aerobic bacteria in gallbladder bile in patients with and without gallbladder cancer. MATERIAL AND METHODS: A microbiological analysis of bile and pathological study was performed in 608 gallbladders, obtained during to cholecystectomies performed to 513 women and 95 men aged 44 years old as a mean. RESULTS: Pathological study showed a chronic cholecystitis in 468 cases (77%), an acute cholecystitis in 140 (33%), cancer in 24 (3.9%) and dysplasia in 5 cases (0.8%). A positive culture was obtained in 22.5% of women and 28.5% of males. Twenty seven percent of women over 30 years old had positive cultures compared with 10% of younger women (p < 0.001). Thirty two percent of acute cholecystitis had positive cultures, compared with 24% of chronic cholecystitis (p = 0.03). E Coli was isolated in 51% of positive cases, Streptococci-Enterococci in 24%, Enterobacter sp in 9%, Klebsiella and Proteus in lower proportions. Salmonella sp was isolated in 4 cases, being all women with chronic cholecystitis. Thirteen of 29 cases with cancer or dysplasia had positive cultures (45%), compared with 25% of patients with inflammatory gallbladder diseases (p = 0.02). Streptococci-Enterococci were isolated in 7 cases and Enterobacter sp in three. CONCLUSIONS: The presence of Salmonella sp in gallbladder bile was not frequent in the studied patients. Its role in the pathogenesis of gallbladder cancer must be reassessed.

Desde la displasia hasta el cáncer de la vesícula biliar

Background: There is scarcity of knowledge about the development of gallbladder cancer. Aim: To study the features of development and progression of gallbladder cancer. Material and methods: Review of histopathological studies of gallbladder obtained in 25,971 cholecytectomies performed in patients aged 45± 16 years, 79% females, between 1993 and 2004. Among these, 210 had a dysplasia not associated to cancer and 1,039 had a gallbladder cancer Clinical and morphological parameters of preneoplastic and neoplastic lesions were analyzed. Ninety five percent of patients were followed. Results: All cases of dysplasia were incidental findings. Metaplasia, dysplasia and carcinoma in situ were present in the adjacent mucosa in 66%, 81% y 69% of gallbladder carcinomas, respectively. Twenty five percent of gallbladders studied were carcinomas (mucous carcinoma in 18% and muscular carcinoma in 7%). Ninety two percent of cases had chronic inflammation in the gallbladder wall. Seventy two percent of mucous carcinomas were not detected macroscopically Five years survival of mucous carcinoma was 92%. There was an association between the intensity of the lesion and the age of the patients. The age difference between chronic cholecystitis and gallbladder cancer was 11 years for women and nine for men. Conclusions: From a morphological standpoint, the period in which a dysplasia becomes a carcinoma is approximately 10years.