Malignant melanoma (MM) is the more aggressive form of skin cancer with a mortality rate in Argentina 1997-2001 = 1.1/100 000 in men and 0.6 in women. BRAF proto-oncogene is focus of intense research; its mutation is one of the main tumor promoters and occurs in approximately 50% of MM. Several drugs with clinical activity on BRAF mutations have been approved. The aim of the study is to evaluate the mutational status of BRAF (exon 15) in cutaneous MM biopsies and its relationship with histopathological characteristics. We carried out an observational, retrospective study of samples fixed in formaldehyde and paraffin embedded; reviewing age, sex, diagnosis, histopathological data, tumor size and percentage, viability for molecular analysis and melanin presence. We evaluated BRAF mutations with PCR/Sanger sequencing. For statistics we used Student's t test, Chi square, Wilcoxon and Fisher's exact test. We were able to purify and sequence 76% (38/49) samples, 13/38 (34%) from women and 25/38 (66%) from men, the median age being 70 years. Most frequent location: thorax 14/35 (40%). Histological type: Superficial spreading 18/38 (47%). Clark's levels, 11/38 (29%): I-II and 27/38 (71%): III, IV and V. Breslow's median: 1.6 mm. Radial growth phase 11/38 (29%) and 27/38 (71%) vertical. Presented mutations 16/38 (42%). As reported by other authors, no association was found between the mutational state of exon 15 and clinical or histopathological parameters.

Lung carcinoma is the main cause of cancer death worldwide. Adenocarcinoma molecular biomarkers have been discovered, and targeted therapies have been developed with encouraging results. The epidermal growth factor receptor gene is one of these biomarkers. Exons 18 to 21 should be studied in patients with advanced adenocarcinoma, who are candidates for treatment with tyrosine kinase inhibitors. The objective was to compare the performance of the determination in large and small samples in daily practice conditions, trying to adjust to published consensus guidelines. A retrospective observational study of 141 cases was carried out, with exons 19 and 21 sequencing. Sample size (small vs. large), including number of satisfactory polymerase chain reaction (PCR), sequencing, deletions, and mutations, were evaluated. In small biopsies, sample type, fragment number, and percentage of tumor per sample were analyzed. The results shown 114/141 (80.8) cases that met selection criteria; 60/114 (53%) were large (surgical) and 54/114 (47%) were small samples (19/54 endoscopic, 17/54 fine needle aspiration clots, 4/54 lymph nodes, 14/54 core and other). All large samples were satisfactory PCR, 56/60 (93%) satisfactory sequencing, and 12/56 (21%) had deletions in exon 19. Small samples were satisfactory PCRs in 50/54 (93%) cases, and satisfactory sequencing in 35/50 (65%), 8/35 (23%) showed alterations in exon 19, and 1/35 (3%) in exon 21. In conclusion, the proportion of samples unfit for the study of the epidermal growth factor receptor gene mutational status increased from 7% in large samples to 35% in small ones. Nineteen small samples were inconclusive, with cell blocks predominating, 10/19 (53%).

Antecedentes: el papel del estudio patologico intraoperatorio (EPI) en cirugia tiroidea ha sido discutido largamente y es todavia motivo de controversia. Objetivo: estimar los resultados del EPI en el diagnostico de malignidad, su relacion con la biopsia por puncion-aspiracion preoperatoria con aguja fina (PAAF) y el estudio patologico diferido (EPD), asi como su contribucion al cambio en la estrategia quirurgica en cirugia tiroidea. Material y metodos: revision retrospectiva de las historias clinicas de 773 pacientes operados por patologia tiroidea entre enero de 2014 y diciembre de 2015. En todos se efectuo EPI y EPD; a 686 (89%) pacientes tambien se les efectuo la biopsia por PAAF preoperatoria. Resultados: los resultados del EPI fueron benigno en 215 pacientes (27,8%), maligno en 419 (54,2%) y no definitivo en 139 (18,0%). Cuando estos resultados fueron comparados con la EPD se encontraron 19 casos (8,8%) de falsos negativos y 4 (0,95%) de falsos positivos. Considerando solo los resultados definitivos, el EPI tuvo sensibilidad 95%, especificidad 98%, valor predictivo positivo 99%, valor predictivo negativo 91% y exactitud 91%. Cuando se comparo el EPI con la PAAF preoperatoria, los valores de sensibilidad mas bajos (44%) correspondieron a las categorias de Bethesda III y IV. El EPI influyo en la estrategia quirurgica en 95 pacientes (12,28%): en 53 (6,8%), la hemitiroidectomia cambio a tiroidectomia total; en 37 (4,8%), el diagnostico de metastasis ganglionares permitio realizar un vaciamiento modificado de cuello, y en 5 (0,6%) ocurrieron ambas situaciones. Conclusion: el EPI tuvo altos valores de utilidad diagnostica cuando se compararon con el EPD. Tambien se correlaciono con la PAAF preoperatoria, pero tuvo menos utilidad en las categorias Bethesda III y IV. El EPI contribuyo a cambiar la decision de tecnica quirurgica en un grupo de pacientes y evitar una segunda operacion

Fil: Mazzei, Paula. Centro de Educacion Medica e Investigaciones Clinicas “Norberto Quirno”; Argentina

Barrett's esophagus (BE) is a risk factor for esophageal adenocarcinoma (EAC) which prognosis depends on the stage at diagnosis. Several scientific societies have developed guidelines for BE surveillance for early detection of malignancy. Adherence to these guidelines includes following appropriate technique and intervals (IV). Technical aspects are difficult to apply and most studies focus on this topic's compliance.

Serrated adenomas (SA) evolve to Colorectal Cancer (CRC) in 15-20% through the serrated pathway. The prevalence is variable (0.8 to 13%) because some lesions are unseen even in case of experienced endoscopists.

Columnar lined epithelium (CLE) known as Barrett Esophagus (BE), the main complication of Gastroesophageal Reflux Disease, is the strongest risk factor for esophageal adenocarcinoma. Its definition varies worldwide according to the inclusion of globet cells (Intestinal Metaplasia-IM) for the diagnosis. Several studies have shown an equal risk for neoplastic progression in patients either with or without IM. However, if the absence of globet cells is a pathologist misdiagnosis, an early stage in the disease progression or sampling error is still unknown.

Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

Purpose The aim of this work was to investigate the potential protective effects of fish oil on the basis of kidney transcriptomic data on a nutritional experimental model. Methods Male weanling Wistar rats were divided into four groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were killed after receiving the diets for 6 days. Total RNA was purified from the right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array. Differentially expressed genes were analyzed. Results All CSVO, CSMO and CDMO rats showed no renal alterations, while all CDVO rats showed renal cortical necrosis. A thorough analysis of the differential expression between groups CSMO and CDMO was carried out. There were no differential genes for p < 0.01. The analysis of the differential expression between groups CSVO and CSMO revealed 32 genes, 11 were over-expressed and 21 were under-expressed in CSMO rats. Conclusions This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.

Background After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on Tissue Micro-Array. Methods Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. Results Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. Conclusions The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1366310812718988

Risk of lymphatic or blood dissemination of colorectal cancer (CRC) limited to the mucosa and superficial submucosa is low. In these cases, Endoscopic Mucosal Resection (EMR) can be considered a treatment alternative. The efficacy and safety of the procedure has been demonstrated, but only few studies report the recurrence rate after the procedures. To evaluate the short and long-term outcomes of EMR of High Grade Dysplasia (HGD) and Intramucosal (IM) Colorectal Cancer. Adults with High Grade Dysplasia (HGD), Intramucosal (IM) or superficial submucosal colorectal cancer who underwent complete EMR using a submucosal saline injection technique were eligible for surveillance. Patients with invasive carcinoma, incomplete EMR, or a nonlifting sign were referred to surgery. The study was carried out in an outpatient GI clinic in Buenos Aires city between 2005 and 2009. The first follow-up endoscopic examination was performed at 3-6 mo after initial endoscopic resection, the second at 12 mo post- EMR, and subsequent surveillance colonoscopic examinations were individualized. The study design was descriptive, retrospective, observational, and cross sectional. Recurrence was defined as the presence of any amount of adenomatous or carcinomatous tissue on follow-up, confirmed by histology at the site of prior resection. VCCSTAT 2.0. 60/394 EMR were diagnosed with HGD, intramucosal or superficial submucosal CRC. Twelve patients were referred to surgery, 18 were lost to follow up, and a total of 30 patients were followed up. Average age was 63 years, 56% were male, and all were white. Sixty-three percent of lesions were polypoid; mean size was 35mm and the rectum was the most frequent location (27%). Mean follow up period was three years. Recurrence was identified in 3 patients (10%, 95% CI 2.1 - 26). The characteristics of patients with recurrent lesions are shown in Table 1.Table 1Characteristics of patients with recurrent lesions.AgeSexMorphologyLocationSizePrimary HistologyTime to recurrence (mo)Recurrent HistologyFollow up (mo)63MPolypoidRectum60mmVillous Adenoma Vienna 43 moTubulovillous adenoma42 mo58MPolypoidAscending20mmTubulovillous adenoma Vienna 46 moTubular adenoma18 mo51FNon PolypoidSigmoid25mmTubulovillous adenoma Vienna 412 moTubular adenoma12 mo Open table in a new tab EMR is an effective technique. Recurrence of lesions occurred in the short term, within 12 months post-EMR. This finding supports the concept that close follow-up endoscopic examinations are necessary for early detection of recurrence.

Adenomatous polyps are predictors of cancer and advanced adenomas. Certain characteristics alert endoscopists about features suggestive of malignancy. Early Colorectal Cancer (CRC) limited to the superficial submucosa, is considered a low-risk disease for lymphatic and blood dissemination. In these cases, Endoscopic Mucosal Resection (EMR) can be considered a therapeutic option. 1) To describe a large series of colonic polyps resected by Endocoscopic Mucosal Resection (EMR), 2) To estimate the prevalence of High Grade Dysplasia (HGD) and early carcinoma in this cohort. reports from EMR of colonic polyps were reviewed Colonoscopies were performed at an outpatient' GI clinic, in Buenos Aires city, between 2004 and 2009. EMR consisted on a submucosal saline injection technique, and main outcome measurement was the description of resected lesions. VCCSTAT 2.0. 394 EMR of 25000 colonoscopies were performed in this period. 48% (190/394) were males. Average age was 56 years (min 24 - max 88 years).All patients were white. 1. With regards polyps 'description the most prevalent findings were : by morphology: non - polyploidy lesions were detected in 70% (95% CI 64 - 75); by location: most lesions were in right colon :43% (95% 39-49); by size: most prevalent size was >10 and ≤ 20 mm in 53% [95% CI 46- 57]; by histology: tubular adenoma was the most prevalent lesion, diagnosed in 33% (95% CI 28- 38). 2. The prevalence of HGD and early carcinoma was 19% (95% CI 15-23). Predominant characteristics of these 68 lesions are described in table 1.Table 1Predominant characteristics of lesions with HGD and early adenocarcinomaMost prevalent characteristics of lesionsN lesions%(95% CI)MorphologyPolypoid3857 (44 - 69)LocationRectum2232 (21 - 44)Size>10 and ≤ 20 mm2133 ( 22 - 46)HistologyHGD3957 (44 - 69) Open table in a new tab According to these results, morphology and location cannot be used to infer histology as benign and malignant lesions are different in these features. HGD and early carcinoma can be detected in fifth of these lesions, so efforts should aim to promote and improve this effective and safe technique.

Esophageal adenocarcinoma (EAC), the worst complication of Gastroesophageal Reflux Disease (GERD) and Barrett's Esophagus (BE), has had an exponential growth in the last four decades. Male gender, white race and age at the time of diagnosis are known risk factors for this disorder. Its correlation with reflux symptoms and whether Intestinal Metaplasia (IM) is a necessary event in the progression of BE to dysplasia and EAC, remain controversial. To estimate the prevalence of: 1. BE and type of metaplasia; 2. Dysplasia and EAC in the BE population; 3. Reflux symptoms in these patients. 21765 upper endoscopy reports of adults seen at the GI outpatients' clinic in Buenos Aires city between 2001 and 2009 were reviewed. Patients with endoscopic suspicion of BE and columnar metaplasia confirmed on histology were included. Intestinal Metaplasia (IM) was the criterion for the diagnosis of BE. Data collection to assess symptoms was based on the information provided in the "reason for study indication". The study design was descriptive, observational, retrospective, and cross sectional. Statistical analysis: VCCSTAT 2.0 617 patients with endoscopic suspicion of BE were analyzed; 63% were male, average age was 49.5 years (range 14 - 85) and all were white. Columnar metaplasia was confirmed in 586 (95%). Hiatal Hernia and esophagitis were described in 44 and 38% of cases respectively. Other endoscopic findings are described in table 1. Histologic findings included: IM in 46% (283/617), Glandular Metaplasia (GM) in 49%(303/617), and chronic esophagitis in 5% (31/617) of cases. Prevalence of IM in the selected population was 1.3% (CI 95% 1.2 - 1.5). Prevalence of Low Grade Dysplasia was 3.8% (CI 95% 1.7 - 7), that of High-Grade Dysplasia was 2.5 (CI 95% 0.9 - 5.4) and that of EAC was 2.1% (CI 95% 0.7 - 4.8) in the BE population; none of these findings were reported in the GM group. Table 1 The prevalence of reflux symptoms (table 2) was 41% (95% CI 35-47). However, complications of GERD (42%) were the main indication for the procedure. Table 2Table 1Endoscopic findingsEndoscopic findingsn%TotalBarrett's Esophagus Union27144617 < 3 cm (short)23838.5 > 3 cm (long)10817.5 Open table in a new tab Table 2Reasons for study indicationIndications for Upper endoscopyn%SymptomsAcidity227.8Heartburn7426Epigastralgia217.5Regurgitation1−ComplicationsControl of esophaqitis1842Surveillance in BE95Control of Antireflux surgery3Others4917.3Total283100 Open table in a new tab Prevalence of BE, Low and High Grade Dysplasia in our setting is in keeping with data reported in the literature. Dysplasia or EAC were only observed in the IM group. In view of these findings and that complications prompted endoscopy in most cases, implementation of preventive strategies emphasizing the importance of a strict protocol for biopsy collection is imperative.

Weanling Sprague-Dawley rats were fed on a choline-deficient diet with hydrogenated vegetable oil and corn oil as lipids develop acute renal failure. Pathogenesis of the latter is controversial and an ischemic mechanism has been proposed. Arachidonic acid derivatives are involved in the regulation of vascular tonus. Vasospasm could be due to an increase in tromboxane A2-mediated vasoconstriction or to a decrease in prostacyclin-induced vasodilatation. Enzymes involved in the synthesis of both compounds are tromboxane A2- and prostacyclin-synthase respectively. The aim of this study was to identify the variable number tandem repeats (VNTR) in the promoter region of prostacyclin synthase gene and verify if there exists a relationship between the occurrence of VNTR in those choline-deficient rats which die because of acute renal failure and those which do not. We verified the presence of the VNTR in the prostacyclin synthase rat gene, but we did not find any difference in the molecular weight of the alleles between experimental and control rats. Renal reparation of the acute kidney injury due to choline deficiency in some rats is not related with differences in VNTR in the promoter region of the prostacyclin synthase gene.

Lymph node mapping and sentinel lymph node biopsy are currently used to stage patients with cutaneous malignant melanoma. Immunohistochemical stains contribute to the detection of micrometastases; however, molecular biology techniques are associated with better diagnostic sensitivity. Sixty sentinel lymph nodes were included in this study. The primary lesions were malignant melanoma stage I or II, with a follow-up of longer than 2 years. Sentinel lymph nodes were studied with hematoxylin–eosin, immunohistochemistry for S-100 and HMB-45, and molecular biology techniques (reverse transcription (RT)-PCR) for the detection of tyrosinase messenger RNA. In 15 of 60 cases (25%), tyrosinase was detected by RT-PCR; three of these cases were also positive by immunohistochemistry. The population was divided into three groups: (i) hematoxylin–eosin−/immunohistochemistry+/molecular biology techniques+ (3 cases); (ii) hematoxylin–eosin−/immunohistochemistry−/molecular biology techniques+ (12 cases); (iii) hematoxylin–eosin−/immunohistochemistry−/molecular biology techniques− (45 cases). Correlation of the groups with overall survival showed the following: (i) 2 of 3 patients died (67%); (ii) 5 of 12 died (42%), and (iii) all 45 patients are alive, with no lymphadenectomy and a median follow-up of 84 months. The inclusion of molecular biology techniques appears to be of great value for the detection of sentinel lymph node micrometastases in patients with cutaneous malignant melanoma. In our series, those patients who showed negativity with all the three methods had a null recurrence rate. Therefore, this triple negativity could be a positive prognostic factor for overall survival. Our findings suggest the possibility of molecular oncological staging, which would allow the selection of patients with submicroscopic metastases for a complete treatment.