Mutational status of PIK3ca oncogene in oral cancer-In the new age of PI3K inhibitors.

In the new age of PI3K inhibitors, the mutational status of PI3Kca oncogene in the Cavity Squamous Cell Carcinoma (OC-SCC) needs further analysis. It is the sixth most common cancer in the world. The aim of this study was to evaluate PI3Kca oncogene mutations and to correlate them with the clinical-histological characteristics of individuals presenting these tumors. We recruited 74 individuals with OC-SCC diagnosis (period 2000-2014). Histological sections were used. DNA was purified; PIK3ca gene exons 9 and 20 were amplified and sequenced. In 49/74 cases (66 %), the complete sequence of both codons was analyzed by Sanger method. We found that 7/49 (14 %) individuals mutated. In exon 9 we found 1/49 (2 %), and in exon 20 M1043I 8/49 (16 %). We have found the coexistence of more than one mutation in a same individual (E542 K and M1043I). A positive association was observed between the mutational status of the codon 9 (E542 K) and the tongue location. In conclusion, the frequency of PI3Kca gene mutation in OC-SCC was 16 %, which is similar to that reported for other populations. We found a mutation not previously described (M1043I) in this pathology. Should its biological effect be confirmed, it must be added to the list of PIK3ca mutations. Total mutations in the PIK3ca were 32 %, with tongue being the site at the greatest risk (E542K-E545K-M1043I). These findings would facilitate the identification of patients with therapeutic targets in the near future.

Tissue alkalosis in cold-ischemia time.

The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain samples have tried to address the impact of cold-ischemia on tissue pH. Here we report pH variations according to time (third-order polynomial model) in mice for liver, kidney and lung samples. Tissue alkalosis in cold-ischemia time may be an underlying mechanism of gene expression changes. Therefore, tissue-pH regulation after organ removal may minimize biological stress in human tissue samples.

Impact of the endoscopic teaching process on colonic adenoma detection.

BACKGROUND: There has been little reported experience in the Latin American hospital setting in relation to the impact of the endoscopic training process on colonoscopy quality. AIMS: To determine the effect that training in the technique of colonoscopy has on adenoma detection in an Argentinian teaching hospital. MATERIAL AND METHOD: Within the time frame of July 2012 and July 2013, 3 physicians received training in colonoscopy from 4 experienced endoscopists. The colonoscopies performed by the supervised trainees were compared with those carried out by the experienced endoscopists. RESULTS: A total of 318 colonoscopies performed by any one of the 3 supervised trainees and 367 carried out by any one of the experienced endoscopists were included. The univariate analysis showed a non-significant difference in the detection rate of adenomas (30.4 vs. 24.7%, P=.09). In the multivariate analysis, the detection rate of adenomas was significantly higher in the colonoscopies performed by one of the 3 trainees (odds ratio = 1.72 [1.19-2.48]). CONCLUSIONS: The supervised involvement of endoscopic trainees has a positive effect on adenoma detection.

The microbiological conditions of carcasses from large game animals in Italy.

This study investigates the microbiological conditions of large game animal carcasses following evisceration. Carcasses of animals (N=291) hunted in the Upper Susa Valley (Italian Alps) were analysed for pH, Aerobic Viable Count (AVC), Enterobacteriaceae, Yersinia spp., Listeria monocytogenes and Salmonella spp. After shooting, evisceration occurred within 60 min in 90.7% of animals and sampling within 90 min in 88.3% of animals. Mean pH values (5.97: ruminants; 5.77: wild boar) were similar to those of regularly slaughtered domestic species. AVC values were highest in animals shot in the abdomen. Within species, AVC and Enterobacteriaceae values did not differ across different shooting-evisceration/sampling times. However, these counts exceeded 5 and 2.5 log, respectively, in 18% of wild boar and 39% of ruminants; the highest values were detected in wild boar. No pathogens were detected in any species. These results reveal inadequate hygiene in game meat handling/harvesting, implicating the need for improved practices.

Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis.

OBJECTIVE: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1). METHODS: liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. RESULTS: Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4(+) and CD20(+) cells were found in the central areas of the portal tracts (portal distribution); (2) CD8(+) cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4(+), CD20(+), and CD8(+) cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56(+) cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. CONCLUSIONS: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.

Linfoma del manto vs. leucemia linfatica crónica atipica: utilización de inmunohistoquímica, citometría de flujo y biología molecular para su correcta tipificación / Mantle cell lymphoma vs. atypical chronic lymphocytic leukemia: use of immunohistochemistry, flow cytometry and molecular biology for their adequate typing

The differential diagnosis of certain B CD5+ lymphoproliferative processes, such as mantle cell lymphoma (MCL) and atypical chronic lymphocytic leukemia (ACLL), is difficult. The aim of this study was to correlate morphological findings, cyclin D1 (cD1) detection by immunohistochemistry (IHC) and immunophenotype by flow cytometry (FC) with the results obtained by molecular biology in this type of neoplasias. We analyzed 20 samples classified as B CD5+ lymphoproliferative processes by FC. PCR was used for t(11;14) bcl-1/IgH determination. Histopathological and IHC studies for cD1 were done in 14 cases. Twelve cases were diagnosed as MCL, with positive cD1 in 5 (5/9), five as ACLL and three as B lymphoproliferative process. PCR revealed t(11;14) in 6/12 MCL and negative results in the other groups (0/8). Molecular biology evidenced translocation in 4/5 MCL positive for cD1 with IHC. The presence of translocation could be demonstrated by IHC and PCR in 7/12 MCL: 4 with both techniques, 2 with PCR alone, and 1 with IHC alone. These findings show a significant association between cD1 by IHC and bcl-1/ IgH gene detection by PCR, which implies that both techniques are complementary for MCL typing.

Algunos procesos linfoproliferativos B CD5+ son de difícil diagnóstico diferencial como es el casodel linfoma del manto (LM) y la leucemia linfocítica crónica atípica (LLCA). El motivo del presenteestudio fue correlacionar los hallazgos morfológicos, la detección de ciclina D1 (cD1) por inmunohistoquímica(IHQ) y el inmunofenotipo por citometría de flujo (CF) con los resultados obtenidos por biología molecular en este tipo de neoplasias. Se estudiaron 20 muestras clasificadas como procesos linfoproliferativos B CD5+ por CF. Se realizó la determinación de t(11;14) bcl-1/IgH por PCR. El estudio histopatológico e IHQ para cD1 se efectuó en 14 casos. Doce casos fueron diagnosticados como LM, con cD1 positiva en 5 (5/9); cinco como LLCA y tres como proceso linfoproliferativo B. Con PCR se observó t(11;14) en 6/12 LM y negatividad en losrestantes grupos (0/8). Se pudo demostrar la presencia de traslocación en 7/12 LM mediante IHQ Y PCR: 4con ambas técnicas, 2 con PCR exclusivamente y 1 con IHQ, evidenciando una alta asociación entre cD1 por IHQ y la detección del gen bcl-1/IgH por PCR, ambas técnicas complementarias en la tipificación de LM.

Rearreglos de genes de cadenas pesadas de las inmunoglobulinas en las gammapatias monoclonales / Immunoglobulin heavy chain gene rearrangements in the monoclonal gammopathies

Las neoplasias de células plasmáticas resultan de la expansión de un clon de células B que secreta inmunoglobulinas, conocido como componente monoclonal o componente M. Las neoplasias malignas incluyen al mieloma múltiple y la macroglobulinemia de Waldenström, y la condición premaligna comprende las gammapatías monoclonales de significado incierto (MGUS). El MGUS presenta un componente monoclonal sin evidencia de mieloma múltiple, macroglobulinemia de Waldenström, amiloidosis primaria u otros desórdenes. El diagnóstico se basa en la combinación de características patológicas, radiológicas y clínicas. Aproximadamente el 25% de las gammapatías monoclonales de significado incierto desarrollarán mieloma múltiple, amiloidosis sistémica, macroglobulinemia o enfermedades linfoproliferativas malignas, indicando que sería una condición premielomatosa. El objetivo del presente trabajo es establecer la utilidad clínica de la inmunofenotipificación por citometría de flujo (CF) y la detección de clonalidad por biología molecular. Se estudiaron 32 pacientes, siete con diagnóstico de mieloma múltiple y veinticinco con gammapatía monoclonal em estudio, los cuales fueron divididos en cuatro grupos basados en los datos clínicos y los resultados de CF. Em el grupo de pacientes con CF no diagnóstica, se realizó la detección de los rearreglos de los genes de las cadenas pesadas de las inmunoglobulinas mediante reacción en cadena de la polimerasa (PCR), detectándose monoclonalidad en el 59% de los casos. El estudio de los rearreglos de los genes de las cadenas pesadas de las IgH mediante PCR incrementa la sensibilidad de detección de monoclonalidad.

[Ischemic colitis after renal transplantation:etiology and pathogenesis]. / Colitis isquémica post-trasplante renal: caso clínico y etiopatogenia.

Ischemic colitis is a well-recognized complication occurring in renal transplant recipients. It has often been associated with cytomegalovirus (CMV) vasculitis. However, the diagnosis of this pathology in the absence of CMV suggests that other etiological factors might be involved. Drugs inducing mesenteric vasoconstriction, such as non-steroidal anti-inflamatory drugs (NSAIDs) and cyclosporine could be related to this entity.

[Influence of diet on lipoprotein profile in familial combined hyperlipidemia affected children]. / Profilo lipoproteico in bambini con iperlipemia combinata familiare. Effetti della dietoterapia.

BACKGROUND: Familial Combined Hyperlipidemia is an inherited disorder affecting cholesterol and triglycerides metabolism, well known myocardial infarction risk factors. The FCHL clinical presentation is usually silent until the third decade although children can be affected, and the more recent opinion is that precocious diagnosis is mandatory in preventing complications. Aim of this study is to examine the effectiveness of the diet therapy (Step-One-Diet) in a group of 13 children affected by Familial Combined Hyperlipidemia. METHODS: The patients have been submitted to a normocaloric diet, 30% fat of the total caloric daily intake according with the Dietary Intervention Study in Children (Step-One-Diet). The patients then have been submitted to a two year-follow-up and lipoprotein levels (total cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B), nutritional status (macro- and micro-nutrients) as well as anthropometric data (height, weight, BMI) have been monitored. RESULTS: Results showed a 10% total cholesterol and 30% triglycerides decrease, Iron and Calcium intake show increased levels approaching to the normal ones after controlled diet, while cholesterol intake was correct on both regimen. The growth parameters show a decrease in weight only in two obese and two overweight patients. CONCLUSIONS: The present study confirmed the effectiveness and safety of the Step-One-Diet in children patients, allowing triglycerides normalization in 60% of the patients, and a 10% cholesterol decrease, in agreement with the complex genetic inheritance of the disease.

[Diagnosis and treatment of Helicobacter pylori infection. Its relationship with gastrointestinal ulcer and antimicrobial resistance]. / Diagnóstico y tratamiento de la infección por Helicobacter pylori. Su relación con la úlcera gastrointestinal y la resistencia a los antimicrobianos.

Reliable data regarding the efficacy of different schemes of triple therapy for the eradication of Helicobacter pylori in our country, are not available. Patients with Helicobacter pylori infection and non-ulcer dyspepsia or active peptic ulcer disease were randomized in three different groups for therapy with, omeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1000 mg, twice daily for one week (OCA 1, 40 patients) and the same treatment but for two weeks in a second group (OCA 2, 40 patients). The third group received omeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg twice daily during one week (OCM, 40 patients). The primary efficacy end point was the eradication of Helicobacter pylori as confirmed by negative urea breath test, 4 weeks after the completion of treatment. Of 120 patients enrolled in the study, 113 met the entry criteria. Of them, 103 completed the treatment. When analyzed by intention to treat, after 4 weeks of finishing the treatment, Helicobacter pylori was eradicated in 92.3% of patients in OCA 1, 89.7% in OCA 2, and 82.8% in OCM. There was no significant difference between the three groups, regarding the eradication efficacy. Side effects were observed more frequently in OCA 2 and OCM groups. Primary resistance to amoxicillin and clarithromycin was not demonstrated, while 20% of cultured strains were resistant to metronidazole. In patients with peptic ulcer disease or non-ulcer dysplasia, triple therapy with omeprazole and two antibiotics is highly effective in the eradication of Helicobacter pylori. One week of OCA therapy is as effective as two weeks of OCA or one week of OCM, with less side effects.

[Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis]. / Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un transplantado renal con hepatitis crónica B y C asintomática.

Hepatocellular carcinoma is a primary tumor complicating liver disease, associated with cirrhosis in 80-90% of the cases. A kidney transplant recipient with chronic B and C viral hepatitis was admitted because of general malaise, renal function impairment and positive AST, ALT and alkaline phosphatase tests, and very high alpha-fetoprotein levels. Ascites, spontaneous bacterial peritonitis and renal failure developed. A CT showed multiple liver masses. Renal failure required hemodialysis. The patient died 17 days after the initial symptoms with hepatic encephalopathy. A postmortem liver biopsy confirmed the diagnosis of cirrhosis and hepatocellular carcinoma (HCC). This report, as well as a few others, shows the accelerated evolution of chronic viral hepatitis in kidney transplant patients and questions the convenience of kidney transplantation and the adequate follow up in chronic viral hepatitis.

Primitive neuroectodermal tumor of the lung.

Primitive neuroectodermal tumors occur most frequently in bone and soft tissue but have been reported in other locations. Primary lung primitive neuroectodermal tumors without pleural or chest wall involvement are extremely rare. We present a case with immunohistochemical and ultrastructural studies and follow-up of the patient. An 18-year-old man presented with hemoptysis. Chest radiographs revealed a right middle lobe mass, and bronchoscopy showed an endobronchial tumor. The lesion was resected by middle lobectomy. After 2 years, a local recurrence was treated by pneumonectomy. The patient died after surgery. Histologically, the tumor was composed of uniform cells with round nuclei and scanty cytoplasm arranged in cohesive lobules with occasional rosette formation. Immunohistochemically, the tumor was positive for vimentin, CD99, neuron-specific enolase, and neurofilaments. Ultrastructural study revealed neurosecretory granules and cytoplasmic processes. Our case shows the value of immunohistochemistry and electron microscopy in the diagnosis of primitive neuroectodermal tumors in unusual locations.

Thyroid hormone changes in males exposed to lead in the Buenos Aires area (Argentina).

The relationship between lead levels in blood (PbB) and hormones T3, T4, T4F and TSH were studied in 75 subjects exposed to lead at work. PbB levels in blood were determined by atomic absorption spectrophotometry and hormones by enzymoimmunoassay. Positive and significant correlations among thyroid hormones and TSH vs blood lead level in the ranges 8-50 and 26-50 micro g dl(-1)were found ('r' between 0.304 and 0.621 and 0.431 and 0.619, respectively). At PbB levels between 8 and 26 micro g dl(-1)significant correlation was only found for TSH (r= 0.731). In the range PbB 50-98 micro g dl(-1), 'r' was significant only for T3 (-0.746) and T4 (-0.514). Significant differences were observed in T4 and T4F levels between exposed and non-exposed groups. The results obtained indicate the need for monitoring thyroid hormones and TSH levels in workers exposed to lead.

Masas de tumores testiculares del síndrome adrenogenital: presentación de un caso / Testicular masses of adrenogenital syndrome: report of a case

Se presenta el caso de un paciente masculino de 19 años de edad que consultó por tumefacción testicular bilateral. El estudio ecográfico reveló formaciones nodulares sólidas, bilaterales. Se efectuó una orquiectomía bilateral. Macroscópicamente se observaron sendas formaciones tumorales de 4,8 y 4 cm de diámetro, sólidas de color marrón claro y bordes lobulados que reemplazaban casi totalmente el parénquima testicular. Se observaban, además pequeños nódulos a nivel del epidímo. Histológicamente las masas testiculares estaban constituídas por células de citoplasma amplio, granular, eosinófilo, con pigmento lipofucsínico intracitoplasmático y ausencia de cristaloides de Reinke con un grado variable de fibrosis interpuesta entre las mismas. Los hallazgos observados correspondían a las masas tumorales del síndrome adrenogenital el que fue confirmado por los datos clínicos y de laboratorio del paciente. El diágnostico de esta rara entidad permite un tratamiento adecuado. Desde el punto de vista morfológico en ausencia de datos clínicos, como en nuestro caso, es necesario hacer el diágnostico diferencial, con tumores de células de Leydig

[Distribution of the genotypes of hepatitis C virus in intravenous drug addicts in Argentina]. / Distribución de los genotipos del virus de la hepatitis C en una población Argentina de drogadictos endovenosos.

Intravenous drug addiction (IVD) is an unfrequent risk factor in Argentina, representing less than 10% of patients (pts) with chronic HCV infection seen in our Unit. In order to study the genotypes (Gt) in IVD and compare them with a non drug addicted control population, 68 pts with a history of IVD were enrolled in this study and compared with 68 non drug addict (NDA) pts with chronic HCV, with similar age and gender distribution. In all pts a liver biopsy was performed. Genotyping was done by INNO LiPA (Innogenetics, Belgium). Mean age in both groups was 35 +/- 7.8 years and 50 were males. No difference was observed between both groups in the prevalence of Gt1a, Gt2a/c and in those with mixed infections. The prevalence of Gt1b in IVD was 19.1% and in NDA 38.2% (p = 0.0228). A highly significant difference was also observed in the prevalence of Gt3a, of 42.6% in IVD and only 11.8% in NDA (p = 0.0001). Gt1a was the second most frequent genotype in IVD pts (26.5%). Simultaneous HIV infection was present in 8 IVD pts (11.8%) and in none of NDA group. Liver biopsies showed a higher prevalence of mild chronic hepatitis in NDA (57.3%) than in IVD (32.4%) (p = 0.0058). Severe chronic hepatitis with advanced fibrosis or cirrhosis was more frequent in the Gt3 of the group with IVD when compared with Gt3 of the NDA group. It can be concluded that in accordance with other geographical areas, Gt3a is far more prevalent in intravenous drugs addicts than in the general population in Argentina where Gt1b is more frequent. Mild forms of chronic hepatitis are less frequent in IVD. In spite of the relatively small group with HCV co-infection with HIV, it seems important to note that 2/8 (25%) showed severe hepatitis C or cirrhosis.

Tumores neuroendocrinos no funcionantes de páncreas / Pancreatic islet cell tumors

Antecedentes: Dentro del capítulo de las neoplasias de páncreas, los tumores insulares no funcionantes son los menos frecuentes. Generalmente son de diagnóstico tardío, de comportamiento biológico maligno en un 80 por ciento de los casos y presentan una tasa de sobrevida a los 5 años de 40 a 60 por ciento. Objetivo: Analizar la experiencia en este tipo de tumores en los últimos 10 años. Material y métodos: Desde enero de 1987 a enero de 1997 se operaron 23 pacientes con tumores insulares de páncreas, de los cuales 10 casos eran no funcionantes, 8 mujeres y 2 varones con una edad promedio de 49,5 años. El tiempo promedio transcurrido entre el comienzo de los síntomas y el diagnóstico fue de 1.5 años. El síntoma más frecuente fue el dolor abdominal. Todos fueron evaluados por ecografía y TAC. Ecoendoscopía en 5 casos, ecografía intraoperatoria en 5, RNM en 3 y angioresonancia en 1. En un caso localmente avanzado se realizó punción diagnóstica preoperatoria. Resultados: Nueve pacientes fueron resecados con criterio curativo, siendo un caso irresecable. Se realizaron una duodenopancreatectomía y 8 esplenopancreatectomías corporocaudales. El promedio de internación fue de 13 días. No se registró mortalidad perioperatoria. La tasa de morbilidad fue del 20 por ciento. El diagnóstico histológico fue tumor insular en los 10 casos, 8 de los cuales fue carcinoma insular. Al momento del análisis 4 pacientes se encontraban vivos y libres de enfermedad, 4 murieron a los 49, 50, 60 y 62 meses y dos fueron perdidos del seguimiento a los 18 y 24 meses. Conclusiones: Debido al comportamiento biológico maligno de estos tumores, la resección es la mejor opción independientemente del tamaño tumoral. Sin embargo, debido a que poseen mejor pronóstico que el adenocarcinoma, siempre se debe realizar diagnóstico histológico en los tumores considerados irresecables

[Great vessel and temporal artery involvement in temporal arteritis]. / Arteritis de células gigantes con compromiso de grandes vasos y arteria temporal.

The importance of this case report resides in the unusual initiation of an arterial inflammatory disease. The patient presented ischemic symptoms and signs with bilateral upper limb claudication and Raynaud's phenomenon, with ulcerations on her left hand. We describe the patient's clinical history, diagnosis and therapy.

Ketoconazole-induced liver damage.

Five cases (four females, one male) of ketoconazole-related liver damage are presented, two of whom died. All patients received ketoconazole (400 mg/day) for various mycoses. In the four women the first signs of hepatotoxicity appeared after four weeks of therapy. One fatal case developed massive necrosis with fulminant liver failure and the other, submassive necrosis. In four cases cholestasis was a prominent finding. Biochemical evidence of biliary stasis may persist for several months, as occurred in the three surviving patients of our series. The two fatal cases continued receiving the drug in spite of its adverse effects. Consequently, repeated evaluation is recommended to detect early signs of liver environment.

[Follicular dendritic cell sarcoma in a lymph node]. / Sarcoma de celulas foliculares dendriticas en ganglio linfatico.

We report the case of a 39 years old man who presented with a rapidly enlarging, painless mass in his left side of the neck. The mass was excised and turned out to be a lymph node. Histologically, it showed a proliferation of oval to spindle cells growing in sheets and fascicles, occasionally forming a storiform pattern. Tumor cells showed large nuclei, dispersed chromatin and small evident nucleoli. Neoplastic cells were positive for immunohistochemical markers vimentin, CD 68, CD 21, CD 35 and R 4/23. Ultrastructural examination showed long cytoplasmatic processes joined by desmosomes. The patient was treated with local radiotherapy and is alive and well 18 months after the excision. Follicular dendritic cell sarcoma is a very unusual tumor that merits wider recognition.