Search

Gallbladder cancer (GBC) should be considered an orphan disease in oncology and represent a unique carcinogenetic model. This review will analyse some of the current aspects of GBC.Chile has the highest incidence and mortality of GBC in the world. Most patients are diagnosed in advanced stages with few treatment options. During the last two decades, little progress has been made in early diagnosis and treatment. At the molecular level, recent access to next-generation sequencing and other techniques for detecting the mutations of multiple genes have made advances in this area.The use of therapies targeted according to the detection of specific molecular alterations is in the early stages of evaluation and could represent a significant advance in the treatment of a large number of patients from developing countries.

The aim of this study was to evaluate the role that laparoscopy plays in the management of gallbladder cancer.From August 2005 to March 2009, 23 patients affected by gallbladder cancer detected after the study of a cholecystectomy specimen underwent laparoscopy as part of their management.Among the patients, 5 underwent only an exploratory laparoscopy, while 11 were converted due to the existence of dense adhesions that precluded a complete exploration. Of the patients with adhesions who underwent conversion, three were unresectable. The remainder underwent a lymphadenectomy and liver resection after conversion. Of the seven who underwent a complete laparoscopic exploration, five had a lymphadenectomy and liver resection done completely by laparoscopy while conversion was needed for two. Conversion was required due to lymphatic metastasis at the hepatic pedicle and the presence of a bile leak. Postoperative time was uneventful, with patients discharged within 3 days of the operation.Laparoscopy may be employed in the management of patients with early forms of gallbladder cancer undergoing reoperation. Although the presence of adhesions may result in inadequate exploration, there is a subset of patients for whom it is possible to perform a complete exam. Furthermore, laparoscopic lymphadenectomy and gallbladder bed resection is a promising technique in well-selected patients.

Background and Objectives: The goal of this study was to evaluate a series of patients with early gallbladder cancer, focusing on the selection of treatment and the role of Rokitansky Aschoff sinus infiltration. Methods: We performed a retrospective analysis of a prospective series of 371 patients with gallbladder cancer. Specimens were reviewed by an independent pathologist to confirm the diagnosis and depth of infiltration and to evaluate the presence of Rokitansky Aschoff sinus involvement. Results: Forty-nine and 45 patients with muscular (pT1b) and mucosal (pT1a) infiltration gallbladder cancer tumors were studied respectively. Simple cholecystectomy was the treatment in all patients, with the exception of 11 patients who underwent further surgery. Rokitansky Aschoff sinus invasion was seen in seven patients with mucosa (pT1a) and three with muscular (pT1b) compromise. The 5-year survival rates of patients with muscular (pT1b) and mucosal (pT1a) infiltration were 87.6% and 86.4%, respectively. Patients with Rokitansky Aschoff involvement had a lower survival rate than those with no involvement in both categories. Conclusions: Early gallbladder cancer is associated with a favorable prognosis and cholecystectomy should be the standard treatment. Despite some patients having a worse prognosis, there are no data to support more aggressive treatment. J. Surg. Oncol. 2009 Wiley-Liss, Inc.

Teneurins are a family of highly conserved pair-rule proteins involved in morphogenesis and development of the central nervous system. Their function in adult tissues and in disease is largely unknown. Recent evidence suggests a role for dysregulated expression of Teneurins in human tumors, but systematic investigations are missing. Here, we investigated Teneurin-2 and Teneurin-4 expression in various cancer cell lines and in ovarian tumor tissues. Teneurin-2 and Teneurin-4 were expressed in most of the breast cancer cell lines tested. Teneurin-4 was also detected in ovarian cancer cell lines, and throughout ovarian tumors and normal ovary tissue. Ovarian tumors with low Teneurin-4 expression showed less differentiated phenotypes and these patients had shorter mean overall survival. Similarly, Teneurin-2 expression correlated with overall survival as well, especially in patients with serous tumors. In the various cell lines, 5-Aza-cytidine-induced changes in DNA methylation did not alter expression of Teneurin-2 and Teneurin-4, despite the existence of predicted CpG islands in both genes. Interestingly, however, we found evidence for the control of Teneurin-2 expression by the oncogenic growth factor FGF8. Furthermore, we identified multiple transcript splicing variants for Teneurin-2 and Teneurin-4, indicating complex gene expression patterns in malignant cells. Finally, downregulation of Teneurin-4 expression using siRNA caused a cell-type dependent increase in proliferation and resistance to cisplatin. Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness. We conclude that Teneurin-2 and Teneurin-4 expression levels could be of prognostic value in ovarian cancer.

Obstructive jaundice secondary to hepatocellular carcinoma fragments migrated to common bile duct Obstructive jaundice is a rare presentation of hepatocellular carcinoma (HC), and when it occurs, usually is due to progressive damage from cirrhosis, or extensive tumor infiltration. Tumor growth through the bile duct is being described with increasing frequency as a cause of obstructive jaundice. Rarely, it may be hepa- tocarcinoma fragments that migrate to the bile duct, obstructing it. We present a case of obstructive jaundice due to migration of fragments of hepatocellular carcinoma to the bile duct in a patient treated 7 years before, for an HC with a curative resection.

Thirty eight percent oftumors were not detected at the macroscopic examination, 52% and 17% had lymph node and bloodvessel involvement, respectively. Fifty six and 46% were positive for p53 and p27, respectively. Noassociation between the expression of both genes and gender, degree of differentiation, lymph node orblood vessel involvement, was observed. Overall five years actuarial survival was 32%. Patients withpositive or negative p53 expression had a 22% and 53% survival, respectively (p =0.05). No associationbetween survival and p27 expression was observed.

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.

29% (range 3%-98%) in gallbladdercancer (p

In the study period, 1239 cases were collected and79% were malignant tumors. In 78% of cases, samples from the tumor and of normal neighaboringtissue, were stored. Twenty six percent of samples were from breast cancer and 22% for digestivetumors. Immunohistochemical expression of vimentin was measured in 30 cases and the expressionof Ki67 an p53 in 20 cases. Thirteen of 15 breast cancer samples had expression of estrogenreceptors. In 30 cases, DNA and RNA extraction was carried out, amplifying s-globin and s-actin.Moreover RNA was extracted from 63 gastric cancer, 30 colon cancer and gallbladder cancersamples, for specific projects.

Biopsy samples of cervical lesions were studied. Sixteen hadlow grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types wereidentified with polymerase chain reaction, dot-blot hybridization and restriction fragment lengthpolymorphism. MSI was determined using a panel of eight highly informative microsatellites.

Biphosphonates reduce the risk of skeletal events and are currently part of standards of therapy in myeloma. Recently, zoledronate and pamidronate have been linked to osteonecrosis of the jaw, specially after surgical dental procedures. We report a 84 year-old man with multiple myeloma who developed spontaneous osteonecrosis of both jaws, after 36 months of therapy with zoledronate with a cumulative dose of 136 mg. We discuss the pathogenic mechanisms, and review the recommendations on prevention and management of this new complication for neoplastic patients under prolonged therapy with biphosphonates.

Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time.Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained.All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K0.75) and substantial for APC (K0.45). No correlation was found between survival time and the methylation of the genes studied.The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

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

Background: Promoter genomic DNA methylation is an important inactivation mechanism of tumor suppressor genes. This genetic-molecular pathway for cancer may separate a subset of patients with different prognoses and eventually different responses to specific therapies. Aim: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with gastric cancer (GC) and the relationship with its morphological features and biological behavior. Material and methods: Forty-seven fresh-frozen GC samples were selected. The methylation-specific PCR (MSP) test was used to analyze promoter methylation status for genes MLH1, CDKN2A (p16), APC, CDH1 (Cadherin E) and FHIT. Follow-up and complete morphological features were obtained for all cases. Results: We found methylation in at least one of the genes studied in 83% of the cases. The frequencies of promoter hypermethylation of MLH1, CDKN2A, APC, CDH1 and FHIT were 31%, 43%, 46%, 80% y 62%, respectively. We found a relationship between APC methylation and good histological differentiation (p=0.03); CDH1 methylation with diffuse type by Lauren and 3 or more metastasic lymph nodes (p

Parathyroid carcinoma is an uncommon cause of primary hyperparathyroidism; however, when this condition is severe, cancer must be suspected. We report on a 28-year-old male with severe hypercalcemia, cachexia, acute pancreatitis, urolithiasis, anemia and a severe skelletal involvement with multiple fractures. The patient had a 4-cm parathyroid tumor, that was surgically excised, along with the ipsilateral thyroid lobe. During the postoperative period, he had a severe and prolonged hungry bone syndrome, with a slow recovery of fractures, with functional and anatomical sequelae in the extremities. PTH levels were adequate for the serum calcium during the 16 months of follow-up (Rev Méd Chile 2005; 133; 77-81)

Background: There is a very strong documented correlation between the appearance of cancer cells in blood and occurrence of metastasis in gastrointestinal cancer. Aim: To determine MUC1, CK19, CK20 and CEA mRNA expression in bone marrow of patients with gallbladder cancer and evaluate its clinical significance. Material and methods: Sixty eight samples were analyzed, 38 bone marrow samples of gallbladder cancer patients, 20 healthy donors, and 10 frozen samples of gallbladder cancer. Nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) was used to analyze mRNA expression. Results: All frozen tumors were positive for CEA, CK19, and MUC1 mRNA and 70% were positive for CK20. Seventeen of 20 donor samples were positive for MUC1 and only one sample from donors was positive for both CK20 and CK19 mRNA. Among the 38 blood and bone marrow samples of gallbladder cancer patients, the expression of MUC1, CK19, CK20, and CEA, mRNA was 60.5% (23/38), 31.6% (12/38), 7.9% (3/38), and 7.9% (3/38), respectively. Disregarding the MUC1 results. 37% (14/38), 13% (5/38) and 5% (2/38) were positive for one, two and three markers respectively. Not significant differences were found in survival with a follow up to 12 months. Conclusion: Our results indicate that the molecular detection of tumor cells in bone marrow in patients with gallbladder carcinoma is technically possible, being CEA, CK19 and CK20 gene expression the best markers. The MUC1 gene expression marker was highly unspecific and it should not been considered. The detection of bone marrow micrometastasis might be helpful in prognosis and the selection of clinical treatment but a larger series with a longer follow-up should be studied (Rev Méd Chile 2004; 132: 1489-98).

Background: Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms. Aim: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior. Material and methods: Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT. Results: We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHIT were 41.4%, 11.4%, 52.9%, 70% y 42.9%, respectively. We found a relationship between CDKN2A methylation 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 larger tumor size (p

Background: The clinical and morphological characterization of the subserous gallbladder carcinomas is controversial. Aim: To study the prognostic importance of DNA content of subserous gallbladder carcinoma. Material and methods: We studied 104 females aged 60±12 years old and 16 men aged 70±13 years old. In all of them diagnosis was established after mapping of cholecystectomy sample and had a complete clinical follow up. DNA content was measured by flow cytometry. Results: All tumors were adenocarcinoma, and only 16% were well differentiated. Aneuploidy was observed in 29 cases (26%) with DNA index fluctuating between 1.1 and 1.8. Lymphatic vessel tumor involvement was present in 16 of 22 cases with aneuploidy and in 22 of 46 diploid tumors (p= 0.05). Eighty nine percent of aneuploid tumors were detected macroscopically and 11% were unapparent. Five years survival was non significantly better among patients with diploid tumors than in patients with aneuploid tumors (45 and 28%, respectively, p= 0.2). The histological differentiation was the only variable significantly associated with survival. Conclusions: Aneuploidy is present in 26% of subserous gallbladder carcinoma. It is not related with any of the morphological or clinical variables studied in this series of patients (Rev Méd Chile 2004; 132: 794-800)

Background: Chile has a high frequency of gallbladder cancer. Polyps are common lesions of gallbladder mucosa but there is little information about their morphological features. Aim: To report the clinical and pathological features of 219 gallbladder polyps. Material and methods: Cholecystectomies samples in which a polypoid lesion was diagnosed microscopically. In all cases, complete clinical information and digitalized images of the complete surgical specimens was reviewed. Results: In a period of 10 years, 21.412 gallbladders 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 done only 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% were adenomas. Seventy five percent of non-neoplastic polyps were located in the proximal half of the gallbladder and 88% of adenomas in the distal half. Ninety five percent of non-neoplastic polyps 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. Eight adenomas were associated with an adenocarcinoma, two had less than 5 mm lenght. Mean age of patients with adenomas associated to cancer was higher than patients with pure adenomas (64.6 and 44.3 years respectively, p >0.001). Conclusions: There are size and location differences between non neoplastic polyps and adenomas. Adenomas associated to cancer may measure less than 5 mm. Therefore the polyp size criteria to decide surgical behavior in symptomatic gallstone patients may be misleading (Rev Méd Chile 2004; 132: 673-9)

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.

Background: Multifocal chronic gastritis, associated to intestinal metaplasia, is considered a preneoplastic lesion, closely associated to intestinal type gastric cancer. Aim: To study the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) in areas of chronic gastritis and intestinal metaplasia in gastric biopsies of patients without cancer. Material and methods: Gastric biopsy samples from 34 patients without cancer (22 with multifocal atrophic gastritis and 12 with diffuse antral gastritis), were studied. Glands from areas of chonic gastritis and intestinal metaplasia and lymphocytes, were collected using laser microdissection of paraffin embedded samples. The analysis of 15 mono and dinucleotide microsatellites was used to assess LOH and MSI. Results: LOH and MSI were found in some of the markers in 55% (12/22) and 59% (13/22) of cases with intestinal metaplasia, respectively. Only one of 12 areas with diffuse atrophic gastritis had MSI and a different area had LOH (p

Gastric cancer is the leading cause of cancer deaths in the general population in Chile, with mortality rates as high as 33.7 per 105 in males in the IX region. A chain of genetic and morphological events precedes the intestinal type of gastric carcinoma. One of them is the called multifocal atrophic gastritis often associated with intestinal metaplasia. Aim: To study the frequency of microsatellite instability (MSI) and loss of heterocigozity (LOH) in neoplastic and preneoplastic lesions of gastric carcinoma, especially intestinal metaplasia. Material and methods: Ninety four gastric cancer biopsies were studied using laser capture microdissection, to obtain well defined cell populations from paraffin-embedded tissues: lymphocytes (control DNA), intestinal metaplasia and gastric cancer areas. Primer flanking microsatellite 15 highly polymorphic regions were used to study MSI and LOH. Radioactive PCR products were electrophoresed and exposed for autoradiography. Results: LOH was observed in 83% of gastric carcinomas and in 54% areas containing intestinal metaplasia. The most commonly altered regions were the CA repeat associated with the p53 gene and the 3p21 region. High grade MSI was observed in 11.7% of gastric cancer preparations and 17% of intestinal metaplasia associated to cancer with MSI-H phenotype. Conclusions: MSI and LOH were frequently observed in intestinal metaplasia glands in patients with gastric carcinoma. The frequency of MSI-H phenotype in gastric patients was slightly lower than the one described in sporadic colorectal cancer not associated to HNPCC. The high incidence of genetic lesions in intestinal metaplasia area, support the idea that intestinal metaplasia is a genetically highly unstable cell population (Rev Méd Chile 2003; 131: 1227-36).

Background: In the current model for the development of gastric cancer, regions of multifocal atrophic gastritis give rise to intestinal metaplasia, dysplasia and finally, adenocarcinoma. Aim: To study the frequency and characteristics of TP53 gene mutations in preneoplastic and neoplastic lesions of the stomach. Material and methods: DNA sequencing of the TP53 gene was performed in 46 patients with gastric carcinoma. Normal mucosa, intestinal metaplasia and invasive adenocarcinoma tissues were obtained by scraping 6-µm histological sections from formalin-fixed and paraffin-embedded tissue. Results: DNA sequencing of exons 5-9 of the TP53 gene demonstrated a mutation in 31% of patients. These findings were seen both in tumoral tissue (13 cases) and in intestinal metaplasia (2 cases). Most mutations were found in exons 5 and 8, and the majority of them were transitions (10 out of 19 mutations). Discussion: Patients with gastric cancer showed a frequency of TP53 mutations similar to that previously communicated in populations with low gastric cancer risk. Moreover, there was a predominance of transitions, genetic alterations that are identified with carcinogenesis associated with N-nitrosamine compounds. Finally, mutations of TP53 gene were detected in areas of intestinal metaplasia (Rev Med Chile 2003; 131: 359-65).

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 (Rev Méd Chile 2002; 130: 1349-57)

Gallbladder cancer is frequent in Chile, but it is not uniformly mortal. The diagnosis is usually made after a cholecystectomy. indicated for a symptomatic cholelithiasis. Global survival of gallbladder cancer can be as high as 40% at five years. In 69% of women of less than 30 years old, the tumor is detected in early stages. In these cases, cholecystectomy is the curative procedure, with a 90% survival at five years. According to our experience, cholecystectomies should be performed between 40 and 50 years of age in men and between 30 and 40 years in women. The prognostic factors that should be considered are symptoms associated to lithiasis, age, parity, obesity, size of stones and the size of the gallbladder. If the tumor is detected in early stages, the survival is good. The natural history of the disease would change significantly if all women with symptomatic stones were operated (Rev Méd Chile 2002; 130: 1295-1302).

Background: The BCR-ABL fusion gene is the molecular expression of the Philadelphia chromosome. This cytogenetic aberration is the most frequent alteration found in leukemias, which is produced by the translocation t(9;22). Two different fusion proteins are produced depending on the break point (210 kD and 190 kD). The detection of this gene has both diagnostic and prognostic importance, associated with poor prognosis in acute lymphoblastic leukemia (ALL). Aim: To detect BCR-ABL gene sequences in patients with leukemia from the IX Region of Chile. Material and methods: We studied 58 patients: 5 chronic myeloid leukemia (CML), 35 ALL, 15 acute myeloid leukemia (AML) and 3 biphenotypic leukemia. The gene sequences were detected using reverse transcriptase polymerase chain reaction (RT-PCR). Results: BRC-ABL gene sequences were positive in all patients with CML, 2 of 35 ALL (one child and one adult). The remaining patients were negative. We found p210 and p190 co-expression in 2 CML and 1 ALL. Conclusions: Our results are in agreement with other reports. The detection of these and other genetic alterations will allow us to have invaluable diagnostic and prognostic information from our patients with leukemia (Rev Méd Chile 2002; 130: 623-30)

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)

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

Malignant diseases of the digestive tract cause more than 50% of deaths due to cancer in Chile. There is a high incidence of gastric and gallbladder cancer and an increasing frequency of colorectal cancer. P53 tumor suppressor gene has a great importance in carcinogenesis and its alterations are specially important in digestive tract tumors such as colorectal cancer. There is contradictory evidence about the frequency of p53 gene or protein alterations or their biological significance. There is little information about p53 in Chile and it is mostly limited to immunohistochemical studies. This revision analyzes the frequency of p53 alterations in digestive tract tumors in Chile, using immunohistochemical and molecular biology methods. A special emphasis is given to the prognostic importance of this gene (Rev Méd Chile 2000; 128: 1269-78)

Background: Genetic events associated to colorectal carcinoma are well characterized, but there is scanty information about this issue in Chilean subjects. Aim: To determine the frequency and distribution of exons 5, 6, 7, 8 and 9 mutations and the immunohistochemical expression of p53 gene in biopsy samples of colorectal carcinoma. Material and methods: p53 gene exons 5, 6, 7, 8 and 9 were directly sequenced in 42 biopsy samples of colorectal carcinoma. Immunohistochemical expression of p53 was determined in 35 samples. Results: Thirty one discrete mutations (12 transitions, 11 transversions and 8 insertions) were observed in 21 samples (60%). Nine samples had mutations in exon 5, twelve samples had mutations in exon 6, seven samples had mutations in exon 7 and three samples had mutations in exons 8 and 9. Immunohistochemical expression of p53 protein was observed in 18 of 35 cases. There was a high correlation between the genetic alteration and immunohistochemistry, when p53 was expressed in more the 20% of cells. The positive and negative predictive values of p53 expression were 87 and 80% respectively. There was a non significant lower mortality among patients with mutations in their biopsies. Conclusions: These results confirm the involvement of p53 gene mutations in colonic carcinogenesis. Immunohistochemical methods for the detection of p53 protein have a high predictive value (Rev Med Chile 2000; 128: 996-1004)

Background: Helicobacter pylori has been involved in gastric epithelial cell damage and gastric gland loss or atrophy. Aims: to evaluate role of Helicobacter pylori infection in acute and chronic changes of chronic gastritis in a high gastric cancer-risk population. Material and methods: 200 patients with chronic gastritis were selected from pathological files of Temuco Hospital. A complete histopathological protocol was fulfilled considering the presence of infection by Helicobacter pylori-like-organism (HLO), acute and chronic inflammatory infiltrate, epithelial cell damage and epithelial cell regeneration. Results: 82% of patients showed infection by HLO. Moreover, this infection reached a frequency of 92.7% in gastric ulcer patients and 94.4% in duodenal ulcer patients. A statistically significant positive correlation was found between HLO infection and polymorphonuclear infiltrate, Iymphocytic infiltrate, mucus depletion and epithelial regenerative activity. There was not a statistical correlation between HLO infection and atrophy. Finally, 90% of patients with multifocal atrophic gastritis and 100% of patients with diffuse antral gastritis had HLO infection. Conclusions: HLO gastric infection frequently caused acute inflammatory changes in gastric mucosa with chronic gastritis. Sometimes these changes were severe, with marked polymorphonuclear migration throughout epithelium and severe epithelial cell damage. Recovery of these changes could be considered as a goal in Helicobacter pylori eradication therapy decision

Background: Gallbladder cancer frequency and mortality renders it one of the most important neoplastic diseases in Chile. P53 tumor suppressor gene has been studied in most types of cancer, but there is scarce information about it in gallbladder cancer. Aim: To study the frequency of P53 gene mutation in gallbladder cancer in the ninth region of Chile. Material and methods: In 25 pathological samples of gallbladder cancer, the direct amplification and sequencing of p53 gene exons 5,6,7,8-8 was possible. Results: Seventeen punctual mutations were observed in 13 cases (52%). There were 10 transitions, 5 transversions, one insertion (codon 194) and one deletion (codon 186). Eight cases had mutations in exon 5, six had mutations in exon 6, two had mutations in exon 7 and one had mutations in exons 8-9. In 14 of 25 cases, gene p53 protein was positive. When immunohistochemical expression of gene p53 protein was positive in more than 20% of cells, there was a high correlation between genetic alterations and immunohistochemical expression of the protein, with a specificity, sensitivity, positive and negative predictive values over 80%. Conclusions: P53 gene mutation is observed in a high proportion of gallbladder cancers at it can be accurately detected with conventional immunohistochemical techniques. The importance of this gene in the genesis of this carcinoma should be determined studying preneoplastic lesions and early carcinomas

Background: p53/p21WAF1/CIP1 and mdm-2 proteins play an important role in cell cycle regulation. The study of the pathogenesis of gastric cancer is important to understand how these tumors progress during their natural history. Aim: To study the relationship between the immunohistochemical expression of p53/p21WAF1/CIP1 and mdm-2 and cell proliferation in gastric cancer. Material and methods: Fifty one gastrectomy specimens with gastric cancer were studied using immunohistochemistry for p53/p21WAF1/CIP1 and mdm-2. Cell proliferation was determined by immunolabelling with PCNA and Ki67 antigens. Mitosis figures were counted in 10 high power microscopic fields. Results: Patients from whom gastric cancer specimens were obtained had a mean age of 59.3 years. Ki67 and mitosis counting showed the highest correlation index with proliferation indexes studied. No correlation was found between the expression of protein complex p53/p21WAF1/CIP1 and mdm-2 and morphological characteristics of gastric tumors. Mdm-2 protein overexpression was the only marker that showed an independent correlation with cell proliferation. Moreover, mdm-2 positive tumors showed the highest proliferation indexes when p53 was not immunohistochemically over-expressed, as determined by PCNA labelling index. Conclusions: In gastric cancer, a direct correlation between mdm-2 overexpression and cell proliferation was observed. Moreover, the fact that mdm-2 positive tumors showed the highest cell proliferation when p53 was not overexpressed, entitles us to hypothesize that mdm-2 overexpression could play a major role in gastric carcinogenesis.

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

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.