[show abstract][hide abstract] ABSTRACT: Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarray and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently found in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers.
Epigenetics: official journal of the DNA Methylation Society 11/2013; 9(2). · 4.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The molecular mechanisms involved in the pathogenesis of GBC remain poorly understood. The vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and is an attractive target for cancer therapy. We characterized VEGF-A expression in advanced GBC and its relation to clinicopathologic features. VEGF-A expression was examined by immunohistochemistry in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 chronic cholecystitis. The cases were classified as low or high expression to evaluate the association of VEGF-A expression level with clinicopathologic variables. The Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analyzed by the log-rank test. High expression of VEGF-A was observed in 81% (183/224) of tumors and 5.1% (2/39) of chronic cholecystitis (P<0.0001). The VEGF-A expression had a significant relationship with histologic grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF-A is associated with a poor prognosis in patients with advanced GBC (P=0.0116). Our results indicate that VEGF-A is highly expressed in GBC and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 10/2013; · 1.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29-95). In more than half of the cases (114/190; 60 %), the tumor was inapparent by gross examination. In 81 cases (42.6 %), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis. Intraepithelial extension into Rokitansky-Aschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (99 %) were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1 %, respectively) were not statistically different from that of the muscle-abutting group (89.7 % and 88.2 % ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39 %) died of disease, whereas only 6 of the 154 patients (4 %) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90 % 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2013; · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Context.-Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. Objective.-To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma. Design.-Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P < .05, and Kaplan-Meier curves were constructed for survival analysis. Results.-Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P = .02). Conclusions.-Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.
Archives of pathology & laboratory medicine 04/2013; 137(4):552-7. · 2.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cervical cancer is a leading cause of cancer deaths in women worldwide and infection by high-risk human papillomavirus types is a precursor event. The cellular FLICE-like inhibitory protein (c-FLIP) has been found to be overexpressed in several types of cancers and could be associated with cervical cancer progression because of its ability to inhibit the apoptotic process. To detect c-FLIP expression in cervical cancer, an immunohistochemical staining was performed, using tissue microarrays, on a series of 536 archival biopsy samples, including normal cervical tissues, low-grade and high-grade squamous intraepithelial lesions, and squamous cervical carcinomas. The epithelium in the normal cervix and low-grade squamous intraepithelial lesions mainly stained negatively for c-FLIP, whereas high-grade intraepithelial lesions and cancer samples showed an elevated expression of c-FLIP. A direct association was observed between the increasing grade of the lesion and the intensity of c-FLIP staining, in which the frequency of intense c-FLIP expression increased from 12.5% in the normal tissue to 82.1% in the cervical cancer tissue. An increased expression of c-FLIP may be an important factor in the progression of cervical cancer. This finding could aid in identifying patients with preneoplastic lesions at greater risk of developing cervical cancer. c-FLIP expression in cervical tissue may be a potential cervical cancer progression marker.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2013; · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Context.- Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Design.- Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Results.- Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Conclusions.- Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.
Archives of pathology & laboratory medicine 02/2013; 137(2):245-250. · 2.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines.
Immunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression.
Our results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 121/137). No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall infiltration level, or histological differentiation (P < 0.05). In vitro treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB cancer cells (P < 0.001).
Our findings confirm the upregulation of this signaling pathway in gallbladder carcinoma and provide a rationale for the potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder carcinoma.
OncoTargets and Therapy 01/2013; 6:1373-1384. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gallbladder cancer is an infrequent neoplasia with noticeable geographical variations in its incidence around the world. In Chile, it is the main cause of death owing to cancer in women over 40 years old, with mortality rates up to 16.5 per 100,000 cases. The prognosis is poor with few therapeutic options; in advanced cases there is only a 10% survival at 5 years.Several studies mention the possible role of DNA methylation in gallbladder carcinogenesis. This epigenetic modification affects tumor suppressor genes involved in regulation pathways, cell cycle control, cell adhesion and extracellular matrix degradation, in a sequential and cumulative way. Determining DNA methylation patterns would allow them to be used as biomarkers for the early detection, diagnosis, prognosis and/or therapeutic selection in gallbladder cancer.
[show abstract][hide abstract] ABSTRACT: We describe a clinicopathologically distinct subtype of cholecystitis, the extensively calcific version of which has been presented in the clinical literature as "porcelain gallbladder (PG)." This cholecystitis, which we propose to refer to as hyalinizing cholecystitis (HC), is characterized by dense, paucicellular hyaline fibrosis transforming the gallbladder (GB) wall into a relatively thin and uniform band. The process diffusely effaces most of the normal structures of GB, and some cases show calcifications. To determine the clinicopathologic associations of HC, we systematically analyzed 4231 cholecystectomies (606 of which had carcinoma) histopathologically, in addition to a targeted search in our databases. Ninety-six cases of HC were identified (1.6% of cholecystectomies). Patients with HC were a decade older than ordinary cholecystitis patients (56 vs. 47; P<0.001), suggesting that HC may be a long-term complication of chronic injury in some patients. Calcifications of variable amounts and degrees were identified in two thirds of the cases. In addition, 10 cases showed diffuse marked calcifications and were considered separately as "complete porcelain" GB. Thirty-eight HC cases had carcinoma with a calculated frequency of 15% and an odds ratio of cancer risk of 4.6. Only 42% of the invasive cases were associated with calcifications; none of the 10 diffusely calcific cases had carcinoma. HC-related carcinomas were challenging diagnostically. They did not form distinct masses or any significant thickening (mean thickness, 2.6 vs. 4.0 mm in ordinary adenocarcinomas; P<0.002). Microscopically, they had widely scattered and bland-appearing glands embedded in the thin band of hyaline stroma of HC, commonly showing a disappearing lining, leaving behind the granular, necrotic intraluminal debris (regression) with or without calcifications, which could be the only sign of cancer in some sections. The morphologic features that allowed the recognition of these glands as malignant included their longitudinal axis parallel to the surface, their irregular contours, clear cytoplasm with distinct borders, nuclear irregularities, and washed-off chromatin. Surface epithelium, if preserved (and it was not in most cases), typically showed carcinoma in situ of either denuding or micropapillary types. HC-associated carcinomas, with a median survival of 7 months, appeared to have a clinical course at least as aggressive as that of regular carcinomas (median survival 12 months; P=0.02). In conclusion, HC is a distinct clinicopathologic entity, which is often associated with carcinoma, and the carcinomas arising from this group are often very subtle and prone to misdiagnosis microscopically. As HC is typically devoid of epithelium, any glandular elements on the wall of HC should be regarded as a suspect for carcinoma. This study also confirms recent findings in the radiology literature-it is not the complete (diffusely calcific) PG that is associated with cancer. Instead, a distinct, histopathologically defined form of cholecystitis, HC with minimal or no calcifications (incomplete PG), is associated with invasive carcinoma. Thus, imaging protocols ought to focus on the correlates of HC rather than fixating on calcifications. Further studies into the pathogenesis of this process and its mechanisms of progression to carcinoma are warranted.
The American journal of surgical pathology 06/2011; 35(8):1104-13. · 4.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25–99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26–81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had ‘advanced’ (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0–20), and 6 were alive (median=64 months, range 5–112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder carcinomas. The incidence of adenosquamous carcinoma (defined as 25–99% of the tumor being squamous) was 4%, and that of pure squamous cell carcinoma (without any documented invasive glandular component) was 1%. Pure squamous cell carcinomas often showed prominent keratinization. The overall prognosis of adenosquamous carcinoma/squamous cell carcinoma appears to be even worse than that of ordinary adenocarcinomas. Most patients died within a few months; however, those few who were alive beyond 2 years in this cohort experienced long-term survival.Keywords: adenosquamous; carcinoma; gallbladder; squamous
Modern Pathology 04/2011; 24(8):1069-1078. · 5.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Early gastric cancer corresponds to those tumors that only involve mucosa and submucosa.
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% males), subjected to a gastrectomy for early gastric cancer. Follow up was performed
according to data in the clinical records and death certifi cates obtained at the Chilean National Death Registry.
Results: Five years global survival of patients was 91%. Lymph node involvement was more common
among tumors bigger than 35 mm, with a low degree of differentiation and among those tumors classifi ed as
diffuse according to Lauren. Survival was signifi cantly 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 fi ve years survival. Bigger tumors, those with a low degree of differentiation
and those with lymph node involvement are associated with lower survival rates.
Revista Chilena de Cirugia 04/2011; 63(2-63):162-169. · 0.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: The degree of tumor infi ltration 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 certifi cates 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% males),
were analyzed. Mean follow up ranged from 1 to 206 months. Five and 10 years actuarial survival was 39
and 34%, respectively. The pathological predictors of survival were microscopic tumor stage, tumor size
and location, Bormann classifi cation, infi ltration 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.
Revista Chilena de Cirugia 04/2011; 63(2-63):154-161. · 0.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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 pathological 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%, the tumor was devoid of lymph node involvement. These later patients were followed for a median of 64 months with a 71% five years actuarial survival. Bivariate analysis identified age, tumor size, gastric wall infiltration, 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 wall infiltration, 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% of gastrectomies for gastric cancer and have a 71% five years actuarial survival. Gastric wall infiltration, pathological degree of differentiation tumor size and lymphovascular involvement are independent prognostic factors.
Revista medica de Chile 04/2011; 139(4):432-8. · 0.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gleason pathological score in prostate cancer is an important prognostic indicator. However, the concordance between the score of trans rectal needle biopsies and the final score of the surgical piece may be variable.
To analyze the concordance between Gleason scores of trans rectal prostate biopsies and those of the surgical piece obtained after prostatectomy.
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.
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% of biopsies, respectively.
Gleason scores of trans rectal biopsies and those of the surgical piece were concordant in 68% of cases in this series of pathological records.
Revista medica de Chile 02/2011; 139(2):171-6. · 0.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Revista medica de Chile 12/2010; 138(12):1535-8. · 0.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Malignant appendiceal tumors account for only 0.5% 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 identifi ed. In 93% of patients, the clinical diagnosis was acute appendicitis. Sixty one patients (73%) had a carcinoid tumor, 20 (24%) an adenocarcinoma and three (3%), an adenocarcinoid tumor. Preoperative suspicion of a malignant tumor, level of tumor infi ltration, 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 signifi cantly 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.
Revista Chilena de Cirugia 06/2010; 62(3-3):255-261. · 0.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mycophenolate mofetil (MMF) is an immunosupressor agent frequently used in patients after bone marrow or solid organ transplants. The most common adverse reactions of the drug are gastrointestinal, specially diarrhea and vomiting. We report a 53-year-old male, that received a heart transplant receiving immunosuppression with cyclosporine, mycophenolate mofetil and prednisone. Six months after the transplant, the patient started with diarrhea, anorexia and weight loss. A duodenal biopsy showed villous atrophy. Celiac disease and the presence of parasites were discarded. Mycophenolate mofetil was discontinued and one week later, diarrhea subsided. Two months later the patient was asymptomatic and recovered weight. A new duodenal biopsy showed absence of villous atrophy.
Revista medica de Chile 05/2010; 138(5):590-4. · 0.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: El cáncer de colon y recto (CCR) es actualmente la cuarta causa de muerte por cáncer en Chile. Su incidencia, sin embargo, está aumentando continuamente en nuestra población. El objetivo de este estudio es describir aspectos morfológicos y clínicos de pacientes resecados por CCR. Estudio de cohorte retrospectiva. Se estudiaron 322 pacientes intervenidos por CCR entre 1987 y 2003 en el Hospital Hernán Henríquez Aravena de Temuco. Las variables clínicas y morfológicas estudiadas (todas ellas analizadas para los subgrupos de sujetos con tumores de colon y de recto) fueron edad, género, localización tumoral, forma y tamaño tumoral, nivel de infiltración, tipo histológico, grado de diferenciación histológico y compromiso tumoral de nodos linfáticos. Se utilizaron estadísticas descriptivas y analíticas; aplicando chi-cuadrado de Pearson y exacto de Fisher para las variables categóricas; y, T-test para variables
continuas. La mediana de edad fue de 66 años, con promedio de edad para tumores de colon derecho (CD), transverso (CT), izquierdo (CI) y recto fue 62,2, 64,6, 64, y 64,4 años respectivamente (p=0,53). En CD e CI se verificaron 57% y 47% de mujeres respectivamente (p<0,05). El 69% de los casos correspondió a tumores de colon (24% CD, 4% CT y 41% CI) y 31% a tumores de recto. El tamaño tumoral promedio fue 67,2± 33,1 mm CD, 53,5± 19,7 mm CT, 44,1± 22,3 mm. CI y 41,5± 17,5 mm en recto (p<0,001). En CD la forma tipo Bormann I se observó en el 57% mientras que en CI lesiones anulares y ulceradas en 45% en CI. Se encontró 75% de tumores moderadamente diferenciados; correspondiendo el 82% a adenocarcinomas, 16% adenocarcinoma mucinoso y 2% carcinoma de células en anillo de sello. El 76% correspondió a tumores T3 y T4. Se encontró compromiso tumoral de nodos linfáticos en 39% de los cuales el 95% correspondían a tumores T3-T4. Se verificaron a nivel regional para pacientes con CCR las variables clínicas y morfológicas descritas en la literatura.
International Journal of Morphology 01/2010; 28(2-2):393-398. · 0.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.
Pathology International 07/2006; 56(6):309-14. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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 (K > 0.75) and substantial for APC (K > 0.45). 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.
Journal of Gastroenterology 04/2006; 41(3):269-75. · 3.79 Impact Factor