Tratamento da diabetes mellitus tipo 2 e comorbidades hepáticas: relato de caso e revisão da literatura / The challenge of treating diabetes mellitus type 2 oral antidiabetic agent whenliver comorbidities represent a problem: case report and literature review

JUSTIFICATIVA E OBJETIVOS: A resistência à insulina (RI) desempenha papel fundamental na etiopatogenia do diabetes mellitus tipo 2 (DM2). A hiperinsulinemia compensatória impede a adequada metabolização dos ácidos graxos, levando ao acúmulo de gordura no hepatócito. A doença hepática gordurosa não alcoólica (DHGNA), na qual a esteatose hepática é a expressão clínica mais comum, têm alta incidência entre os portadores de DM2. Este estudo teve como objetivo discutir os riscos de lesão hepatocelular quando o fígado é exposto a doenças graves e o potencial de hepatotoxicidade de um grupo específico de fármacos.RELATO DO CASO: Paciente do sexo masculino, 51 anos, portador de DM2 e de psoríase numular. História de uso moderado de bebidas alcoólicas por longo período com risco de desenvolver doença hepática alcoólica (DHA). Acresce sorologia positiva para hepatite pelo vírus C (VHC). O fígado palpável, a confirmação da hepatomegalia em exame ultrassonográfico e a elevação das aminotransferases denunciam afecção hepática. CONCLUSÃO: As interações entre o DM2, DHGNA, DHA, VHC e a psoríase, bem como a toxicidade potencial cruzada dos fármacos indicados para o tratamento dessas comorbidades, representam risco real de agressão hepatocelular. A análise comparativa do perfil de segurança dos antidiabéticos orais (ADO) permite eleger os inibidores da dipeptidilpeptidase 4 (i DPP4) como os fármacos de menor potencial de lesão hepática, considerando que não são, em geral, substratos para o sistema do citocromo CYP450 e não atuam como indutores ou inibidores deste sistema com ações metabolicamente apreciáveis.

BACKGROUND AND OBJECTIVES: Insulin resistance (IR) plays a key role in the pathogenesis of type 2 diabetes mellitus (DM2). Compensatory hyperinsulinemia prevents the proper metabolism of fatty acids, leading to accumulation of fat in hepatocytes. The non-alcoholic fatty liver disease (NAFLD) in which hepatic steatosis is the most common clinical expression, has a high incidence among DM2 patients. This paper aims to discuss the risk of hepatocellular injury when the liver is exposed to serious diseases, and the potential hepatotoxicity of a specific group of drugs. CASE REPORT: Male, 51 year-old patient, with DM2 and nummular psoriasis with a history of moderate use of alcoholic beverages for long periods at risk of developing alcoholic liver disease (ALD), and positive serology for hepatitis C virus (HCV). The liver was palpable, the confirmation of hepatomegaly in ultrasound and elevated aminotransferases show liver disease. CONCLUSION: The interactions between DM2, NAFLD,ALD, HCV and psoriasis, as well as the potential cross-toxicity of drugs indicated for the treatment of these comorbidities, represent real risk of hepatocellular injury. The comparative analysis of the safety profile of oral antidiabetic (OAD) drugs allows the election of dipeptidyl peptidase 4 inhibitors (DPP4 i) as the drugs of lower liver damage potential, considering that generally they are not substrates for the CYP450 system and do not work as inducers or inhibitors of this system with substantial metabolic actions.

Safety and efficacy of large balloon sphincteroplasty in a third care hospital.

BACKGROUND AND AIMS: large balloon sphincteroplasty (LBS) associated with sphincterotomy (ES) has gained acceptance as a useful tool in extracting difficult bile duct stones. Our purpose was to evaluate the efficacy and safety of LBS with balloons > or = 10 mm in clinical practice setting. PATIENTS AND METHODS: unicentre prospective study in a tertiary care hospital. All patients who underwent LBS associated with ES between July 2007 and March 2011 were included prospectively in a database recording clinical aspects, procedure data, outcome and complications.Success is the main outcome defined as complete stone removal documented by absence of any filling defect during a final occlusion cholangiogram and absence of clinical or radiological findings after the ERCP consistent with remaining stones. Complications as pancreatitis, cholangitis, post-ERCP bleeding, perforation and others were also measured. RESULTS: one hundred twenty procedures were made in 109 patients with balloons ranging from 10 to 20 mm. Success rate was 91% in the first attempt and 96.7% after two procedures. Mechanical lithotripsy was only needed in one case (0.8%). Complication rate was 4.2% due to five cases of post-ERCP bleeding in high risk patients. CONCLUSION: large balloon sphincteroplasty associated to sphincterotomy in clinical practice is a very effective and safe technique.

Dilatación con balón asociada a esfinterotomía, evaluación de eficacia y seguridad en un hospital terciario / Safety and efficacy of large balloon sphincteroplasty in a third care hospital

Introducción y objetivos: la dilatación con balón de gran tamaño asociada a esfinterotomía es un recurso cada vez más utilizado en la extracción de coledocolitiasis de gran tamaño. El objetivo de este estudio es evaluar la eficacia y seguridad de la dilatación con balones mayores de 10 mm en un entorno de práctica clínica habitual. Pacientes y métodos: estudio prospectivo en un hospital terciario. Todos los pacientes en los que se realizó dilatación con balón mayor de 10 mm asociado a esfinterotomía entre julio de 2007 y marzo de 2011 se incluyeron prospectivamente en una base de datos incluyendo aspectos clínicos, del procedimiento, resultados y complicaciones. El éxito del procedimiento se definió como la extracción de todos los cálculos presentes documentada como ausencia de defectos de repleción en la colangiografía final y la ausencia de signos clínicos y/o radiológicos tras la CPRE sugestivos de persistencia de litiasis. La presencia de pancreatitis, colangitis, perforación y hemorragia post-CPRE también se documentó. Resultados: se realizaron 120 procedimientos en 109 pacientes diferentes, con balones entre 10 y 20 mm de diámetro. La tasa de éxito fue del 91% en el primer intento y del 96,7% tras dos procedimientos. La litotricia mecánica solo se necesitó en un caso (0,8%). La tasa de complicaciones fue del 4,2% debido a cinco casos de hemorragia post-CPRE en pacientes de alto riesgo de sangrado. Conclusión: la dilatación con balón asociada a esfinterotomía en condiciones de práctica clínica habitual muestra una tasa de éxito excelente con un índice de complicaciones reducido(AU)

Background and aims: large balloon sphincteroplasty (LBS) associated with sphincterotomy (ES) has gained acceptance as a useful tool in extracting difficult bile duct stones. Our purpose was to evaluate the efficacy and safety of LBS with balloons >=10 mm in clinical practice setting. Patients and methods: unicentre prospective study in a tertiary care hospital. All patients who underwent LBS associated with ES between July 2007 and March 2011 were included prospectively in a database recording clinical aspects, procedure data, outcome and complications. Success is the main outcome defined as complete stone removal documented by absence of any filling defect during a final occlusion cholangiogram and absence of clinical or radiological findings after the ERCP consistent with remaining stones. Complications as pancreatitis, cholangitis, post-ERCP bleeding, perforation and others were also measured. Results: one hundred twenty procedures were made in 109 patients with balloons ranging from 10 to 20 mm. Success rate was 91% in the first attempt and 96.7% after two procedures. Mechanical lithotripsy was only needed in one case (0.8%). Complication rate was 4.2% due to five cases of post-ERCP bleeding in high risk patients. Conclusion: large balloon sphincteroplasty associated to sphincterotomy in clinical practice is a very effective and safe technique(AU)

[Signet ring cell carcinoma of the ampulla of Vater]. / Carcinoma de células en anillo de sello de la ampolla de Vater.

INTRODUCTION: Signet ring cell carcinoma of the ampulla of Vater is a rare entity and less than 20 cases have been described in the literature. We report the cases of two patients with this disease and provide a literature review of previous studies. CASE REPORT: We describe two patients with obstructive jaundice. Abdominal ultrasonography and abdominal computed tomography showed dilatation of the intrahepatic and common bile duct. Duodenoscopy indicated a protruding mass on the ampulla of Vater. Histopathological examination showed round cells and their nuclei were located on one side with prominent signet-ring features. One patient underwent a cephalic pancreatoduodenectomy with lymphadenectomy and the other a total pancreatectomy. DISCUSSION: Signet ring cell carcinoma of the ampulla of Vater has only been described in isolated cases in the literature. Therefore, the clinicopathological features and prognosis of this disease have not yet been well defined.

Carcinoma de células en anillo de sello de la ampolla de Vater / Signet ring cell carcinoma of the ampulla of Vater

Introducción El carcinoma de células en anillo de sello de la ampolla de Vater es una entidad infrecuente, con menos de 20 casos descritos en la literatura. El objetivo de este artículo es presentar dos pacientes con esta patología y realizar una revisión de los estudios previos. Observación clínica Los dos pacientes ingresaron por ictericia obstructiva. En la ecografía y la tomografía computarizada abdominales se apreció una dilatación de la vía biliar intra y extrahepática. En la duodenoscopia, se visualizó una masa excrecente de la ampolla de Vater que, histológicamente, presentaba células con características típicas de células en anillo de sello. Se realizaron una duodenopancreatectomía cefálica con linfadenectomía y una pancreatectomía total respectivamente. Discusión El carcinoma de células en anillo de sello de la ampolla de Vater ha sido descrito únicamente en casos aislados en la literatura. Por este motivo, sus características clínicopatológicas y su pronóstico aún no están bien definidos (AU)

Introduction: Signet ring cell carcinoma of the ampulla of Vater is a rare entity and less than20 cases have been described in the literature. We report the cases of two patients with thisdisease and provide a literature review of previous studies. Case report: We describe two patients with obstructive jaundice. Abdominal ultrasonographyand abdominal computed tomography showed dilatation of the intrahepatic and common bileduct. Duodenoscopy indicated a protruding mass on the ampulla of Vater. Histopathologicalexamination showed round cells and their nuclei were located on one side with prominentsignet-ring features. One patient underwent a cephalic pancreatoduodenectomy with lymphadenectomyand the other a total pancreatectomy. Discussion: Signet ring cell carcinoma of the ampulla of Vater has only been described in isolatedcases in the literature. Therefore, the clinicopathological features and prognosis of this diseasehave not yet been well defined (AU)

[Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts]. / Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies. Although inhibition of synthesis of GAG and the recovery of enzyme activity with small molecules also may play a role in the management of MPS, the breakthrough is the currently available intravenous ERT. ERT radically changed the setting for treatment of mucopolysaccharidosis I, II and VI in the last decade., Benefits can even be extended soon to MPS IV A (ERT for this condition is already in clinical development), with prediction for treatment of MPS III A and the cognitive deficit in MPS II by administration of the enzyme directly into the central nervous system (CNS). A large number of Brazilian services, from all regions of the country, already have experience with ERT for MPS I, II and VI. This experience was gained not only by treating patients but also with the participation of some groups in clinical trials involving ERT for these conditions. Summing up the three types of MPS, more than 250 patients have already been treated with ERT in Brazil. The experience of professionals coupled to the data available in international literature, allowed us to elaborate this document, produced with the goal of bringing together and harmonize the information available for the treatment of these severe and progressive diseases, which, fortunately, are now treatable, a situation which bring new perspectives for Brazilian patients, affected by these conditions.