Gallbladder cancer who is really cured?

BACKGROUND: Although gallbladder cancer (GBCA) is characterized by a dismal prognosis, there is a proportion of patients who are cured. The aim of this study was to analyze the profile of these patients. METHODS: A database was queried for patients who underwent curative resection with a follow-up of at least 5 years. Patients were prospectively treated and registered by the same surgical team. A multivariate regression analysis was used to identify factors associated with long-term survival. RESULTS: From 1988 to 2013, 461 patients were evaluated and 112 who underwent resection were analyzed. Among the patients, five year survival was 57% while lymph node and liver compromise were the only independent factors associated with survival. On the other hand, the elapsed time between the cholecystectomy and the resection, the differentiation grade and the level of wall invasion did not have an independent effect on the prognosis. CONCLUSION: Despite its poor prognosis, a subset of patients can be cured of GBCA. R0 resection of patients without lymph and liver infiltration are key to GBCA survival.

Laparoscopic management of incidental gallbladder cancer.

BACKGROUND: The laparoscopic cholecystectomy has allowed the detection of an increasing number of incidental gallbladder cancers (IGBC). Although laparoscopy is employed in the management of a variety of abdominal tumors, its use in gallbladder cancer is reduced and controversial. This study analyzes the role of laparoscopy in gallbladder cancer with the focus in IGBC. METHOD: We evaluated our prospective series of 51 patients with an IGBC who were treated by laparoscopy between 2006 and 2016 at the Clinica Alemana in Santiago, Chile. RESULTS: The series comprised 7 men and 44 women. Age ranged from 43 to 76 years (mean age 60). Regarding wall involvement, 29 patients had a T2 tumor, which was the most common. 8 and 14 patients had T1b and T3 tumors, respectively. Of the patients, 17 underwent only laparoscopic exploration. This was due to the presence tumor dissemination not being observed in the preoperative staging. 10 patients had to be converted to complete the resection, whereas 24 patients were laparoscopically resected. The quality of the resected material was not different between those who were converted and those who were treated by laparoscopy. In the laparoscopic group, the average number of harvested lymph nodes was 7.9, not statistically different from the converted group. The mean of hospital stay in the laparoscopic group (4.3 days) was significantly lower than the converted group. CONCLUSIONS: Laparoscopy has been shown to be a safe and feasible method for the management of IGBC. This method not only allows for a complete exploration, identifying a previously unseen residual tumor, but also makes it possible to accomplish the same oncology objectives as the open procedure. Therefore, laparoscopy should be considered a valid alternative in the management of IGBC.

Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study.

OBJECTIVE: To determine the prognostic impact of tumor location in gallbladder cancer. BACKGROUND: Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. METHODS: For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated. RESULTS: Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. CONCLUSIONS: After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.

Gallbladder cancer in Chile: what have we learned?

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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 low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer.

[BRAF gene mutation in wild-type KRAS patients with colorectal cancers]. / Mutación del gen BRAF en pacientes con cánceres de colon y recto con KRAS no mutado.

BACKGROUND: In colorectal cancer, BRAF and KRAS mutation are mutually exclusive, but both are independent prognostic factors for the disease. AIM: To determine the frequency of BRAF V600E mutation in colorectal cancer. MATERIAL AND METHODS: A KRAS mutation study was carried out in 100 tissue samples of primary and metastatic adenocarcinomas of colon and rectum from patients aged 61.1 ± 62 years (56 women). Negative KRAS mutation cases underwent study of BRAF V600E mutation by restriction fragment length polymorphism (RFLP) and direct sequencing. RESULTS: Primary tumors were located in the colon and rectum in 88 and six cases respectively. Five were liver metastases and in one case, the sample location was undetermined. Forty two samples were KRAS positive (mutated). In 12 of the 58 KRAS negative (wild type) samples, the V600E mutation in codon 15 of the BRAF gene was demonstrated. No differences in the frequency and distribution of mutations, stratified by gender, age, primary tumor versus metastasis, or tumor location were observed. CONCLUSIONS: Twelve percent of KRAS negative colorectal cancer samples showed BRAF gene mutation. Considering that 42% of samples have a KRAS mutation, 54% of patients should not respond to therapies with monoclonal antibodies directed against epidermic growth factor (EGFR) pathway.

[KRAS gene mutation in colorectal cancer]. / Mutación del gen KRAS en el cáncer de colon y recto.

BACKGROUND: KRAS oncogene is involved in colorectal carcinogenesis in 22 to 45% of cases. AIM: To determine the frequency, types and distribution of KRAS mutations in colorectal cancer. MATERIAL AND METHODS: KRAS mutations studies were carried out in primary tumors and metastases of colo-rectal cancer from 56 women aged 60 ± 14 years and 53 men aged 61 ± 11 years. Formalin fixed and paraffin embedded tissue samples were evaluated using RFLP (Restriction Fragment Length Polymorphism) and direct sequencing. RESULTS: Primary tumors were located in the colon and rectum in 82 (75.2%) and 24 cases (20%), respectively. In three cases the extraction site of the tumor sample was unknown. In 46 cases (42.2%) KRAS mutations were demonstrated. The main point mutations were located in codon 12 (80.4%), G12D (39.1%), G12V (24.2%), G12S (6.5%), G12A (4.3%); G12C (4.3%), G12R (2.1%) and 19.6% at codon 13 (G13D). No differences were demonstrated in the frequency and distribution of mutations by gender, age, primary versus metastatic tumors or tumor location. CONCLUSIONS: In this series, 42% of colorectal cancer tissue samples had KRAS mutations. Their frequency and distribution are similar to those reported in the literature, except for G12C mutation.

[HER2 gene amplification and overexpression in advanced gastric cancer]. / Expresión y amplificación del gen HER2 en el cáncer gástrico avanzado.

BACKGROUND: Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies. AIM: To determine the frequency of HER2 gene overexpression and amplification in advanced gastric cancer. MATERIAL AND METHODS: One hundred nine advanced gastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62 ± 12 years respectively, were selected. Three histological patterns (diffuse, intestinal and mixed) were recognized. Automated immunohistochemistry was performed with monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridization (FISH) for HER2 was performed in positive cases. RESULTS: In 39% of cases, immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15, 36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal type and mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISH was performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification was positive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance between immunohistochemical staining and in situ hybridization was 85%. CONCLUSIONS: In advanced gastric cancer, HER2 gene overexpression or amplification was observed in 11% and 12% of cases, respectively.

[Quality of DNA from archival pathological samples of gallbladder cancer]. / ¿Es posible utilizar las muestras de colecistectomías con cáncer en investigación?: Calidad del ADN de muestras obtenidas del sistema público y privado de salud.

BACKGROUND: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. AIM: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. MATERIAL AND METHODS: One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (ß-globin products of 110, 268 and 501 base pairs). RESULTS: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. CONCLUSIONS: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

Gallbladder cancer: role of laparoscopy in the management of potentially resectable tumors.

BACKGROUND: The aim of this study was to evaluate the role that laparoscopy plays in the management of gallbladder cancer. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Early gallbladder cancer: is further treatment necessary?

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.

Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. EXPERIMENTAL DESIGN: We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. RESULTS: SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P < 0.001). Real-time quantitative PCR confirmed significant overexpression of CTGF transcripts in microdissected primary GBC (P < 0.05), but not in metastatic GBC, compared with nonneoplastic gallbladder epithelium. By immunohistochemistry, 66 of 182 (36%) GBC had high CTGF antigen labeling, which was significantly associated with better survival on univariate analysis (P = 0.0069, log-rank test). CONCLUSIONS: An unbiased analysis of the GBC transcriptome by SAGE has identified CTGF expression as a predictive biomarker of favorable prognosis in this malignancy. The SAGE libraries from GBC and nonneoplastic gallbladder mucosa are publicly available at the Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.

Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer.

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.

Promoter methylation profile in gallbladder cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. CONCLUSIONS: 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.

Gallbladder cancer: an analysis of a series of 139 patients with invasion restricted to the subserosal layer.

The goal was to study our experience in the management of a series of patients with a potentially curative subserosal gallbladder cancer who were prospectively treated by the authors. Between April 1988 and July 2004, 139 patients were enrolled in our prospective database. Of the above, 120 were operated on with an open procedure and the rest with laparoscopic surgery. In only eight patients was the diagnosis suspected before the cholecystectomy. The majority of tumors were adenocarcinoma. Six patients had an epidermoid tumor, and one had a carcinosarcoma. Of the patients, 74 underwent reoperation, while in 55 (70.2%) it was possible to perform an extended cholecystectomy with a curative aim. Operative mortality was 0%, and operative morbidity was 16%. Lymph node metastases were found in 10 (18.8%), while in 7 (13.2%) the liver was involved. The overall survival rate was 67.7%, while in those who underwent resection, the survival rate was 77%. Through the use of a multivariate analysis, the presence of lymph node metastasis was found to be an independent factor with respect to prognosis. The feasibility of performing an extended cholecystectomy in patients with gallbladder cancer and invasion of the subserosal layer allows for a good survival rate. The presence of lymph node metastases represents the main poor prognosis factor, and some type of adjuvant therapy should be studied in this particular group.

Infarto agudo al miocardio secundario a disección coronaria espontánea biarterial: reporte de un caso y revisión de literatura / Acute myocardial infarction due to spontaneous two vessel coronary artery dissection

Resumen: La disección coronaria espontánea ha surgido como una causa interesante y poco reconocida de síndrome coronario agudo no aterosclerótico. Ocurre más frecuentemente en mujeres jóvenes, donde de forma importante puede asociarse a anomalías arteriales no coronarias. La clave para un tratamiento oportuno es el diagnóstico precoz que impida su evolución a cuadros más severos. Se presenta el caso de una mujer de 36 años con un síndrome coronario agudo secundario a una disección coronaria espontánea bi-arterial que evolucionó de forma grave a una insuficiencia cardíaca aguda. El objetivo es informar un cuadro poco usual y proporcionar evidencia que respalde el cómo debe enfrentarse.

Abstract: Spontaneous coronary dissection is an important cause of acute non-atherosclerotic coronary syndrome. It occurs more frequently in young women, often without significantly associated coronary arterial anomalies. Early diagnosis is a key to prompt treatment, in order to prevent severe complications. We report the case of a 36-year-old woman with an acute coronary syndrome secondary to spontaneous bi-arterial coronary dissection progressing to severe acute heart failure. A discussion of the management of this condition is included.

Somatic Mutations of PI3K in Early and Advanced Gallbladder Cancer: Additional Options for an Orphan Cancer.

Gallbladder cancer (GBC) is the second-leading cause of death from malignant tumors in Chilean women. The phosphatidylinositol 3-kinase (PI3K) pathway is involved in proliferation, cell survival, and growth. We investigated mutations in exons 9 and 20 of the PI3K gene in GBC. Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC. The patient group consisted of 110 women and 20 men, and mutations were found in 22 cases (16.9%). Of these, 14 cases had mutations in exon 9 (63.6%) (E542K, 64%; E545K, 29%; and E545G, 7%) and 8 in exon 20 (37.4%; H1047L, 50%; H1047R, 50%). No differences were noted in the frequency and type of mutations analyzed by sex, age, or histologic features. We observed mutations in 22% of the early-stage GBC and 14.6% of the advanced cases. In this series of GBC, 17% of cases were noted as having mutations in either exons 9 or 20 of PI3K. These results suggest that therapeutic testing of inhibitors of the PI3K/AKT pathway may be of benefit in advanced GBC patients.

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder.

BACKGROUND: Gallbladder cancer is very common in Chile and is the leading cause of cancer deaths in women aged over 40 years. However, there is limited information about the molecular changes involved in its pathogenesis. Microsatellite analysis was performed using polymerase chain reaction (PCR)-based assays to identify genetic loci that were altered in neoplastic and preneoplastic conditions of early and advanced gallbladder cancer. Our findings were then correlated with clinicopathological variables and survival time. METHODS: We selected 59 surgical specimens of gallbladder adenocarcinomas (29 early cancers and 30 advanced cancers) and 22 surgical specimens from patients with chronic cholecystitis from a high-risk area for gallbladder cancer (Temuco, Chile). Laser capture microdissection (LCM) was used to harvest tumor cells and preneoplastic lesions. Microsatellite analysis was performed using 13 different markers. The tumors and preneoplastic lesions were also examined with immunohistochemistry for hMLH1, hMSH2, and hMSH6. RESULTS: We found that 10% (6/59) of gallbladder cancers showed high-frequency microsatellite instability (MSI-H), with identical proportions in both early and advanced cancers. In premalignant lesions adjacent to the six MSI-H tumors, we detected instability in two of six examples of intestinal metaplasia (33%) and five of six examples of dysplasia (83%). All MSI-H cases showed an altered pattern with the antibodies studied. MSI status was not associated with survival or other clinicopathological features. No MSI or immunohistochemical alterations were found in the chronic cholecystitis group. CONCLUSIONS: Microsatellite instability was observed in equal proportions in early and late cancers, and it was also found in premalignant lesions, indicating that inactivation of mismatch repair genes occurs early in gallbladder carcinogenesis.

Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer.

BACKGROUND: PTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR pathway, which is frequently altered in human cancers including gallbladder cancer (GBC). To determine the frequency of PTEN expression in GBC and to establish its relation to clinical and morphological parameters and survival in GBC. METHODS: The immunohistochemical expression of PTEN was studied in 108 GBC. All the cases included areas of non-tumor mucosa adjacent to the tumor. RESULTS: The group was comprised of 108 patients, 91 women (84.3%) and 17 men (15.7%) with an average age of 65.2 years (SD ± 12.3 years). Thirty-five cases (33%) were early carcinomas (EC) and the remaining 73 (67%) were advanced cases (AC). All the internal controls were positive (moderate or intense in 96.3%). Only in three AC (4.1%) was there a complete absence of PTEN immunohistochemical expression. There were no significant differences in relation between PTEN expression and tumor infiltration or degree of differentiation. The three patients with PTEN inactivation died before 10 months; however, the other patients with AC had a survival of 53% at 10 months. DISCUSSION: Loss of PTEN expression was observed in 4.1% of the advanced GBC. All the patients with this alteration died before 10 months. PTEN inactivation could be a rare event, but with a poor prognosis in advanced GBC.

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.