Compromiso ganglionar extracapsular en pacientes con cáncer gástrico: determinación del valor pronóstico / Prognostic value of extracapsular lymph node involvement among patients with gastric cancer

Background: Extracapsular lymph node involvement has a negative prognosis in malignant tumors. Aim: To assess the prognostic importance of extracapsular lymph node involvement in patients with gastric cancer with lymph node metastases. Material and Methods: Clinical and morphological features and survival of patients with gastric cancer and lymph node involvement operated between 1986 and 2003, were analyzed. Patients with and without extracapsular involvement were compared. Results: During the study period, 459 gastrectomies were performed, 312 patients (68 percent) had lymph node involvement and 144 (31 percent) had extracapsular involvement. Patients with and without extracapsular involvement were followed for a median of 10 (range 1 to 120) and 41 (range 1 to 193) months, respectively. Five years actuarial survival for patients with and without extracapsular involvement was 23 and 40 percent respectively. Extracapsular lymph node involvement and level of wall infiltration were identified as prognostic factors using a multivariate analysis. Conclusions: Extracapsular lymph node involvement is an independent risk factor for mortality among patients with gastric cancer.

Factores asociados al pronóstico de pacientes operados por cáncer gástrico avanzado / Pathological factors associated with survival in advanced gastric cancer

Background: The degree of tumor infiltration and lymph node involvement are the most relevant pathological features to determine prognosis of advanced gastric cancer. Aim: To determine the association between clinical and pathological features of advanced gastric cancer and patient survival. Material and Methods: The pathological records of patients with advanced gastric cancer subjected to gastrectomy and lymph node excision between 1986 and 2007 were analyzed. Follow up was performed according to data in the clinical records and death certificates obtained at the Chilean National Death Registry. The main outcome analyzed was survival after surgery. Results: The records of 299 patients aged 62 +/- 11 years (68 percent males), were analyzed. Mean follow up ranged from 1 to 206 months. Five and 10 years actuarial survival was 39 and 34 percent, respectively. The pathological predictors of survival were microscopic tumor stage, tumor size and location, Bormann classification, infiltration level, degree of differentiation, pathological type of tumor according to Lauren, Ming y Nakamura, lymph node involvement and the absence of residual tumor after surgical excision. Conclusions: The pathological study of the surgical piece in advanced gastric cancer has important prognostic implications.

Introducción: El estudio de la pieza operatoria de pacientes resecados por cáncer gástrico (CG) ha permitido identificar variables anatomo-patológicas con valor pronóstico en la supervivencia (SV) y recurrencia de estos pacientes, siendo el compromiso ganglionar linfático y nivel de infiltración tumoral, los factores más relevantes identificados. El objetivo de este estudio es determinar asociación entre variables clínicas y morfológicas con la SV de pacientes resecados por CG avanzado (CGA). Material y Método: Estudio de cohorte retrospectiva. Se estudiaron variables clínicas y morfológicas de 299 pacientes operados por CGA entre enero de 1986-diciembre de 2001. Los datos fueron obtenidos desde la Unidad de Anatomía Patológica del Hospital Hernán Henríquez Aravena de Temuco. Se aplicó estadística descriptiva y analítica; confección de curvas de supervivencia, y finalmente se aplicaron modelos de regresión logística para realizar ajuste, calcular odds ratios y sus respectivos intervalos de confianza de 95 por ciento. Resultados: La cohorte tuvo una mediana de edad de 63 años y el 68 por ciento de ella correspondió al género masculino. Con una mediana de seguimiento de 21 meses (1 a 206), se observó una SV actuarial global a 5 y 10 años de 39 por ciento y 34 por ciento respectivamente. En el análisis bivariado, se verificó asociación con la SV en: etapa tumoral macroscópica, localization y tamaño tumoral, tipo según Bormann, nivel de infiltración, grado de diferenciación histológico, tipo histológico según Lauren, Ming y Nakamura, estado ganglionar linfático (N), estadio TNM y resultado de la resección realizada. Conclusiones: Las variables mencionadas deben ser cuidadosamente evaluadas al momento de decidir terapias en pacientes con CGA.

Factores morfológicos asociados al pronóstico de pacientes operados por cáncer gástrico incipiente / Pathological features associated with survival in early gastric cancer

Background: Early gastric cancer corresponds to those tumors that only involve mucosa and submuco-sa. It is associated with a high survival rate. Aim: To determine pathological factors associated with survival in early gastric cancer. Material and Methods: Analysis of pathological records of 106 patients, with a median age of 63 years (60 percent> males), subjected to a gastrectomy for early gastric cancer. Follow up was performed according to data in the clinical records and death certificates obtained at the Chilean National Death Registry. Results: Five years global survival of patients was 91 percento. Lymph node involvement was more common among tumors bigger than 35 mm, with a low degree of differentiation and among those tumors classified as diffuse according to Lauren. Survival was significantly lower for bigger tumors, those with of a low degree of differentiation, diffuse tumors according to Lauren and those with lymph node involvement. Conclusions: Early gastric cancer has a high five years survival. Bigger tumors, those with a low degree of differentiation and those with lymph node involvement are associated with lower survival rates.

Introducción: El cáncer gástrico incipiente (CGI) es aquel que compromete la mucosa o submucosa gástrica independientemente del compromiso ganglionar linfático, estimándose su prevalencia en Chile inferior al 20 por cientoo. El objetivo de este estudio es determinar prevalencia de CGI y asociación de variables biode-mográficas y morfológicas con la supervivencia (SV) de pacientes resecados por CGI. Material y Método: Estudio de cohorte retrospectiva. Se estudiaron variables biodemográficas y morfológicas de 106 pacientes resecados por CGI entre 1986-2007. Se aplicó estadística descriptiva y analítica; confección de curvas de SV, y finalmente se aplicaron modelos de regresión logística para realizar ajuste, calcular odds ratio y sus respectivos intervalos de confianza de 95 por ciento. Resultados: 15 por ciento correspondió a CGI. La mediana de edad fue 63 años y el 60 por ciento correspondió a género masculino con una SV global a 5 años de 91 por ciento. Se observaron diferencias estadísticas significativas entre tumores mucosos y submucosos en cuanto a la localización tumoral y compromiso linfonodal junto con presentarse el compromiso nodal más frecuentemente en tumores > 35mm poco diferenciados y difusos de Lauren. El análisis multivariado identificó como factores asociados a la SV: tamaño tumoral, grado de diferenciación histológica en su variedad poco diferenciado, tipo difuso de Lauren y compromiso ganglionar linfático. Conclusiones: Se verificó una prevalencia de CGI de 15 por ciento, los que resecados presentan SV de 91 por ciento a 5 años. El compromiso linfonodal es un factor asociado a la SV; y además, se relaciona con tamaño tumoral, tipo histológico según Lauren, grado de diferenciación histológico y nivel de infiltración.

Cáncer gástrico sin compromiso ganglionar linfático (pN0): características demográfico-patológicas y factores pronósticos / Prognostic factors for gastric cancer without lymph node involvement

Background: The absence of lymph node involvement (N0) in gastric cancer is associated with a better survival. However some N0 gastric tumors still have a bad prognosis. Aim: To study demographic and morphological variables associated with prognosis in N0 gastric carcinoma. Material and Methods: Review of pathologica records of a regional general hospital, identifying patients with a N0 gastric cancer surgically excised between 1986 and 2003. Results: In the study period, 459 gastrectomies were performed for gastric cancer and in 32 percent, the tumor was devoid of lymph node involvement. These later patients were followed for a median of 64 months with a 71 percent fve years actuarial survival. Bivariate analysis identifed age, tumor size, gastric wallinfiltration, pathological type according to Lauren and Ming, lymphovascular involvement, number of lymph nodes excised and TNM stage as prognostic values Multivariate analysis disclosed the level of gastric wallinfiltration, the presence of a poorly differentiated tumor, lymphatic vascular involvement, number of excise lymph nodes and tumor size as independent prognostic factors. Conclusions: N0 gastric tumors are found in 32 percent of gastrectomies for gastric cancer and have a 71 percent fve years actuarial survival. Gastric wallinfiltration, pathological degree of differentiation tumor size and lymphovascular involvement are independent prognostic factors.

Puntaje de Gleason en cáncer de próstata: Correlación de la biopsia por punción y prostatectomía radical / Concordance between Gleason scores of trans rectal biopsies and the surgical piece of radical prostatectomy

Background: Gleason pathological score in prostate cancer is an importantprognostic indicator. However, the concordance between the score of trans rectal needle biopsies and the final score of the surgical piece may be variable. Aim: To analyze the concordance between Gleason scores of trans rectal prostate biopsies and those of the surgical piece obtained after prostatectomy. Material and Methods: Retrospective analysis of 168 pathological records of radical prostatectomies, performed between 1993 and 2009. All these patients had also a trans rectal biopsy performed previously. Patients with less than 12 tissue cylinders obtained during the trans rectal biopsy or incomplete data were not included in this analysis. Results: Sixty eight percent of trans rectal biopsies had Gleason scores that were concordant with those of the surgical piece. The score was higher or lower in 27 and 10 percent of biopsies, respectively. Conclusions: Gleason scores of trans rectal biopsies and those of the surgical piece were concordant in 68 percent of cases in this series of pathological records.

Linfoadenitis criptococócica mesentérica: Una rara causa de abdomen agudo. Caso clínico / Mesenteric cryptococcal lymphadenitis: Report of one case

Cryptococcosis is an invasive mycotic infection caused by Cryptococcus neoformans, an encapsulated, yeast-like fungus. It is considered an opportunist infection, since it mainly affects immunocompromised subjects. However there are isolated reports of the infection in immunocompetent subjects. Cryptococcal infection of intra-abdominal organs or tissues is extremely rare. We report a 21-year-old HIV positive male that, during the treatment of a meningeal cryptococcosis, presented a clinical picture of an acute abdomen suggesting acute appendicitis. The patient was operated, finding enlarged mesenteric lymph nodes forming conglomerates and a macroscopically normal appendix. The conglomerated lymph nodes and the appendix were excised. The pathological study of the surgical piece revealed an intra abdominal cryptococcal lymphadenitis and a normal appendix.

Carcinoma de células en anillo de sello gástrico: descripción clínico-morfológica y valor pronóstico / Prognosis of signet ring cell carcinoma of the stomach

Background: Signet ring cell carcinoma of the stomach corresponds to 3 to 39 percent of all gastric malignant tumors, and its prognostic significance is not well known. Aim: To compare the prognosis of signet ring cell carcinoma of the stomach with other types of gastric cancer. Material and Methods: Review of 451 patients operated for gastric carcinoma. Signet ring cell carcinomas were compared with the rest of tumors. Results: One hundred twenty tumors (27 percent) were signet ring cell carcinoma, they were more commonly located in the lower third of the stomach, were less differentiated, bigger and had more lymph nodes involved. Patients with this variety of tumor were younger, more often women and their survival was lower, even when separating incipient and advanced tumors. Conclusions: Signet ring cell carcinoma of the stomach had a worst prognosis that other type of gastric tumors.

Introducción: La incidencia de carcinoma gástrico (CG) de células en anillo de sello (CAS) varía de 3 por ciento a 39 por ciento. Trabajos de supervivencia en pacientes con tumores gástricos reportan resultados contradictorios en cuanto a la importancia pronostica del tipo histológico CAS respecto a los otros tipos histológicos. El objetivo del estudio es describir y evaluar la importancia pronostica del tipo histológico CAS comparado con los carcinomas no anillo de sello (CNAS). Material y Método: Estudio de cohorte retrospectiva. Se estudiaron variables clínicas y morfológicas de 451 pacientes operados por CG en el Hospital Hernán Henríquez Aravena de Temuco entre Enero/1986-Diciembre/2001 agrupándose para el análisis según el diagnóstico histopatológico en CAS y CNAS. Se realizó un análisis exploratorio de los datos y posteriormente se aplicó estadística descriptiva con cálculo de medidas de tendencia central y extrema; y estadísticas analíticas, aplicando Chi cuadrado de Pearson y test exacto de Fisher para variables categóricas, T-Student para variables continuas, Kaplan-Meier y Log-rank test para análisis de supervivencia. Resultados: Un 27 por ciento (120) correspondió a CAS observándose diferencias estadísticamente significativas entre los grupos CAS y CNAS para las siguientes variables: género, edad, localización y tamaño tumoral, grado de diferenciación histológico y compromiso ganglionar linfático. El análisis de supervivencia demostró un peor pronóstico para el grupo de CAS (p = 0,02). En el análisis por separado de tumores incipientes y avanzados respecto del tipo histológico, no observamos diferencias significativas para lesiones incipientes (p = 0,07) mientras que para lesiones avanzadas el CAS se asocia a un pronóstico desfavorable (p < 0,0001). Conclusiones: Observamos en nuestra serie un peor pronóstico asociado al tipo histológico CAS respecto a los otros tipos histológicos (CNAS), información crucial que, aportada al clínico, deberá ser...

Descripción clínico-morfológica y factores pronósticos en carcinomas de apéndice cecal: estudio de cohorte / Appendiceal malignant tumors: review of 84 cases

Background: Malignant appendiceal tumors account for only 0.5 percent of all gastrointestinal tumors and there are usually diagnosed during the pathological study of excised appendices. Aim: To assess the factors influencing the survival of patients with appendiceal carcinomas. Material and Methods: Retrospective review of records of all primary appendiceal carcinomas diagnosed in the pathology unit of a regional hospital between 1993 and 2008. The surgical procedure, clinical history, morphological features of tumor and survival were recorded. Results: Eighty four patients aged 32 ± 15 years (44 women) with appendiceal carcinoma were identified. In 93 percent of patients, the clinical diagnosis was acute appendicitis. Sixty one patients (73 percent) had a carcinoid tumor, 20 (24 percent) an adenocarcinoma and three (3 percent), an adenocarcinoid tumor. Preoperative suspicion of a malignant tumor, level of tumor infiltration, pathological type, involvement of surgical borders, tumor size over 2 cm in the case of carcinoid tumors and the degree of differentiation of adenocarcinomas, had prognostic value. For adenocarcinomas, performing a right hemicolectomy significantly improved survival. Conclusions: Carcinoid tumors are the most common malignant tumor of the appendix. A right hemicolectomy may improve the survival of patients with appendiceal adenocarcinomas.

Introducción: Los tumores malignos del apéndice cecal representan tan sólo el 0,5 por ciento de todas las neoplasias gastrointestinales. Su diagnóstico generalmente no es sospechado por el clínico, siendo su diagnóstico un hallazgo durante el examen de la pieza operatoria. Algunos de estos tumores presentan buena supervivencia con la sola apendicetomía, aunque en ocasiones es necesario realizar tratamientos complementarios. El objetivo de este estudio es determinar la asociación entre variables clínicas y morfológicas con la supervivencia de pacientes con carcinomas del apéndice cecal y analizar el tratamiento quirúrgico realizado. Material y Método: Cohorte retrospectiva de 84 pacientes con carcinomas apendiculares diagnosticados en el Hospital Hernán Henríquez Aravena de Temuco entre los años 1993-2008. Se estudiaron variables clínico-morfológicas, el tratamiento quirúrgico realizado y la supervivencia para estos pacientes. Se utilizó estadística descriptiva y analítica, aplicando Chi-cuadrado y test exacto de Fisher para variables categóricas y T-Student para variables continuas; y prueba Log-rank (Mantel-Cox) para comparación de curvas de supervivencia con un IC de 95 por ciento. Resultados: Del total de apendicectomías (18.563) se verificaron 84 casos (0,45 por ciento); 48 por ciento hombres y 52 por ciento mujeres con una edad promedio de 31,9 +/- 15 años. En el 93 por ciento de los casos el diagnóstico clínico fue apendicitis aguda. Correspondieron a carcinoide, adenocarcinoma y adenocarcinoide en 61 (73 por ciento), 20 (24 por ciento) y 3 (3 por ciento) casos respectivamente. En el análisis bivariado las siguientes variables mostraron asociación pronóstica estadísticamente significativa: sospecha pre-operatoria (p = 0,009), nivel de infiltración tumoral (p = 0,04), tipo histológico (p = 0,009), compromiso de bordes quirúrgicos (p < 0,001), tamaño tumoral > 2 cm en tumores carcinoides (p = 0,001) y grado de diferenciación en adenocarcinomas...

Cáncer gástrico en una región de Chile: comparación de variables clínicas y morfológicas en dos períodos (1986-1995 y 1996-2005) / Changes in morphological an clinical characteristics of gastric cancer from 1986 to 2005

Background: In the last decade, changes in therapy and on the epidemiological and pathological behavior of gastric cancer have occurred in Chile. Aim: To compare the natural history of gastric cancer in two periods (1986-1995 and 1996-2005) in the ninth region of Chile. Material and Methods: Medical records of 563 gastrectomies for gastric cancer, performed between January 1986 and December 2005 and kept at a Pathology Unit of a public hospital, were reviewed. Clinical and morphological variables were analyzed (histological Lauren type, differentiation degree, location and macroscopic type, infiltration level, number of resected and involved lymph nodes). Results: A significant increase in the frequeney of the diffuse type of gastric cancer was observed in the seeond period in study, with a concomitant deerease of the intestinal type. A reduction in tumor size and number of excised lymph nodes was also observed. Conclusions: In the seeond study period, morphological changes in gastric cancer, were observed.

Introducción: El cáncer gástrico (CG) es la primera causa de muerte por cáncer en Chile (tasa de mortalidad general de 19,5 x 10(5) y 24,8 x 10(5) habitantes a nivel nacional y IX Región respectivamente). Se han descrito cambios epidemiológicos, histopatológicos y de tratamiento para CG. El objetivo de este estudio es describir la historia natural del CG en la IX región de Chile comparando dos periodos (1986-1995 y 1996-2005). Material y Método: Cohorte histórica. Se incluyeron todos los casos de gastrectomías por CG de la Unidad de Anatomía Patológica del Hospital Hernán Henríquez Aravena entre Enero de 1986 y Diciembre de 2005 (n = 563). Se estudiaron variables clínicas (edad, género y estadio TNM) y morfológicas (tipo histológico según Lauren, grado de diferenciación, localización y tipo macroscópico de la lesión, nivel de infiltración, número de ganglios resecados y comprometidos por el tumor). Se aplicó estadística descriptiva y analítica usando t-test y ANOVA para variables continuas, chi² y exacto de Fisher para variables categóricas. Resultados: De las características estudiadas, se evidenció un incremento estadísticamente significativo del tipo difuso en el segundo período en estudio a expensas de un decremento del tipo intestinal; así también una disminución en el tamaño tumoral y número de ganglios linfáticos resecados. Conclusiones: Se verificaron cambios morfológicos del CG experimentados a nivel regional en los períodos estudiados.

Validez diagnóstica de la biopsia intraoperatoria en cirugía de lesiones mamarias palpables / Diagnostic value of frozen section biopsy during surgery for breast lesions or neoplasms

Background: During the surgical treatment of breast neoplasms (benign or malignant), frozen section biopsy is frequently requested to assess the kind of lesion and determine the surgical margins. Aim: To assess the diagnostic yield of frozen section breast biopsy. Material and methods: AH the pathological reports of frozen section biopsies and definitive biopsies of 337 women aged 26 to 88 years, operated for suspected breast neoplasms between 2002 and 2006, were reviewed. The sensitivity, specificity and predictive value of frozen section biopsy, were calculated using the definitive biopsy as the gold standard. Results: The definitive biopsy confirmed the presence of cancer in 290 women (86 percent). There were two false negative (0.59 percent) and no false positive frozen section biopsies for cancer detection. The sensibility for cancer detection was 99.3 percent and the specificity 100 percent. The positive predictive value was 100 percent and the negative predictive value 96.1 percent. The diagnosis of phyllodes tumor was missed by frozen section biopsy in three cases. The margins were informed in the 258 frozen section biopsies (79 percent) and in 59 cases (18 percent), these were positive for cancer. Conclusions: Frozen section biopsy is useful and reliable for cancer detection and margin status assessment in breast cancer surgery (RevMéd Chile 2009; 137: 1173-8).

Estudio de patrones de metilación génica en tumores del tubo digestivo / Gene methylation patterns in digestive tumors

Background: The loss of tumor suppresor gene function damages the defensive mechanisms that protect the indemnity of genetic material. Promoter gene methylation is one of the inactivation mechanisms of suppressor genes. Aim: To study the methylation pattern of a group of genes in biopsy samples of gastrointestinal tumors. Material and methods: Forty eight gastric, 25 gallbladder, 24 colon and 6 pancreas cancer biopsy samples were randomly selected. The methylation pattern of CDH1, FHIT, CDKN2A, APC and MLH1 genes, was studied using a specific polymerase chain reaction test for methylation. Demographic, morphological and follow up variables of patients bearing the tumors were also analyzed. Results: The general methylation frequency of CDH1, FHIT, CDKN2A, APC and MLH1 genes was 64.1, 56, 39.8, 18.1 and 34 percent respectively. In gastric cancer samples there was a correlation between APC gene methylation and well differentiated tumors; between CDH1 methylation and Lauren diffuse type and the presence of three or more metastasic lymph nodes; between FHIT, CDKN2A and CDH1 gene methylation and male gender. In ¡ess differentiated gallbladder tumors, the frequency of CDH1 methylation was higher. There was a tendency towards a lower survival in colon and gastric cancer when MLH1 (p =0.07) y CDKN2A (p= 0.06) were methylated, respectively. Conclusions: An abnormal methylation pattern was associated with morphological features in gastric and gallbladder cancer and with a tendency towards a lower survival in colon and gastric cancer.

Estudio del patrón de metilación génico en el cáncer gástrico en Chile / Promoter methylation profile in gastric cancer

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 <0.05); FHIT, CDKN2A and CDH1 methylation and female condition (p <0.04). We also found a non-significant relationship between CDKN2A methylation and better survival (p=0.07). Conclusions: The high frequency promoter methylation found confirms its importance in gastric carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search for new criteria in clinical and therapeutic decision making.

Relación de la genotipificación de Helicobacter pylori con la forma e intensidad de la gastritis en población adulta portadora de patología gástrica benigna / Association between helicobacter pylori genotype and the severity of gastritis in infected adults

Background: The damaging capacity of Helicobacter pylori is variable and depends, in part, on its genetic polymorphism. Aim: To study H pylori genes vacA, cagA and iceA and the relationship of these genotypes with the features of acute damage in chronic gastritis. Material and methods: Gastric endoscopic biopsies were obtained in 75 adults for pathological study and genetic typification of H pylori by specific PCR. Results: In only 64 cases, complete information was available. In 53 of these, there was H pylori infection demonstrated by PCR. Twenty one percent had infection by two or more H pylori strains, vacA gene had genotypes s2/m2, s1/m1 and s1/m2 in 36, 25 and 8% of cases respectively, cagA gene was present in 49% of infected patients. iceA gene had genotypes iceA 1 ad iceA 2 in 15 and 60% of patients respectively. The presence of cagA or alleles s1/m1 and s1/m2 of vacA gene was directly correlated with polymorphonuclear infiltration and the severity of epithelial damage. The genotype s2/m2 of vacA gene was significantly associated with a milder or absent mucosal damage. No association was found between iceA alleles and the pathological features of gastritis. Conclusions: Alleles of vacA and cagA genes of H pilory are associated with the severity of gastric mucosal damage.

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

Background: The CDKN2A gene encodes a cyclin dependent kinase inhibitor, p16, which promotes cell cycle arrest. Methylation of the promoter region trans-criptionally 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.

Alteraciones genéticas en gastritis crónica: Estudio de inestabilidad microsatelital y pérdida de la heterocigocidad / Genetic changes in chronic gastritis: study of microsatellite instability and loss of heterozygosity

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 <0.05 or less, when compared with areas of multifocal atrophic gastritis). Three areas of normal epithelium in patients with multifocal atrophic gastritis, also had alterations. Most of these alterations were concordant with adjacent areas with intestinal metaplasia. Conclusions: LOH and MSI was found in areas of intestinal metaplasia in more than half of the studied cases and in few areas of atrophic gastritis without intestinal metaplasia. These findings suggest that genotypic alterations may precede phenotypic modifications and that intestinal metaplasia is a preneoplastic lesion (Rev Méd Chile 2003; 131: 1365-74).

Inestabilidad microsatelital y pérdida de la heterocigocidad en lesiones neoplásicas y preneoplásicas gástricas / Microsatellite instability and loss of heterozygosity in neoplastic and preneoplastic gastric lesions

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).

Mutación del gen p53 en el cáncer de colon y recto / P53 gene mutation in colorectal cancer

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 percent). 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 percent of cells. The positive and negative predictive values of p53 expression were 87 and 80 percent 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

Heterotopía pancreática: un caso de localización duodenal y coledociana / Heterotopic pancreas: a case of duodenal and common bile duct site

Se describe un caso de heterotopia pancreática de localización duodenal y coledociana en un paciente en el que realizó una colecistectomía electiva por vía tradicional por colecistolitiasis. Durante el transcurso de la cirugía constatamos una dilatación de la vía biliar extrahepática. Por ello, se realizó una colangiografía intraoperatoria, que permitió verificar la existencia de una masa ocupante a nivel de colédoco distal. Se decidió entonces la exploración de la vía biliar para resecar la lesión. El estudio histológico del espécimen fue concluyente de tejido heterotópico pancreático. Después de este procedimiento, se decidió explorar la región de la papila, hecho que significo realizar una duodenotomía longitudinal. Así, se logró observar una masa nodular de un cm de diámetro en la porción medial, que protruía hacia la mucosa duodenal. Se practicó una esfinterotomía y resección de la masa, cuya biopsia contemporánea fue informada como tejido pancreático, compatible con heterotopia. Al mes después de la cirugía se realizó una colangiografía de control a través de la sonda de Kehr, con un paso normal del medio de contraste al duodeno. El curso postoperatorio fue correcto. El control ambulatorio, con un seguimiento de 10 meses, el paciente se encuentra en buenas condiciones

Hepatocarcinoma: descripción de características clínicas verificadas en una región del sur de Chile / Hepatocellular carcinoma: description of clinical features in south region from Chile

Background: Hepatocellular carcinoma is the most frequent primary tumor of the liver. It is associated to chronic liver diseases and has a high prevalence in some regions of Africa and Asia. Aim: To describe the clinical characteristics of patients with hepatocellular carcinoma, admitted to two hospitals of the IX region of southern Chile. Material and methods: Prospective study of 29 consecutive patients admitted to two hospitals in Temuco, Chile. Clinical features, laboratory values and viral markers were analyzed. Results: Eighteen patients were male and ages ranged from 29 to 75 years old. The most frequent presenting symptom was abdominal pain in 21 patients. Seven subjects had a history of alcoholism. Serum bilirubin values ranged from 0.1 to 15.8 mg/dl, alkaline phosphatases ranged from 171 to 3476 U/l, ASAT from 24 to 5400 U/l and alpha feto protein from 1.4 to 350 ng/ml. Two patients had a positive hepatitis B surface antigen and all had negative hepatitis C virus antibodies. Mean tumoral diameter was 9.6 cm and the most common presentation was nodular. Mean survival after the diagnosis was 6.3 months. Conclusions: These patients with hepatocellular carcinoma have a low frequency of positive viral markers and tumors of large sizes on presentation

Mutación del gen p53 en el cáncer de la vesícula biliar / P53 gene mutation in gallbladder cancer

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 percent). 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 percent 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 percent. 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