Synchronous Periampullary Tumors in a Patient With Pancreas Divisum and Neurofibromatosis Type 1.

INTRODUCTION: In this study, we describe for the first time a Neurofibromatosis type 1 patient with pancreas divisum, multiple periampullary tumors and germline pathogenic variants in NF1 and CFTR genes. CASE REPORT: A 62-year-old female NF1 patient presented with weakness, choluria, nausea, and diffuse abdominal pain to an emergency room service. Magnetic resonance imaging revealed an abdominal mass involving the periampullary region and pancreas divisum. After surgical resection, three synchronous neoplasms were detected including two ampullary tumors (adenocarcinoma of the major ampulla and a neuroendocrine tumor of the minor ampulla) and a gastrointestinal stromal tumor (GIST). Germline multigene panel testing (MGPT) identified two pathogenic heterozygous germline variants: NF1 c.838del and CFTR c.1210-34TG[12]T[5]. CONCLUSION: This is the first report of a Neurofibromatosis type 1 patient with pancreas divisum and multiple periampullary tumors harboring pathogenic germline variants in NF1 and CFTR genes. The identification of two germline variants and a developmental anomaly in this patient may explain the unusual and more severe findings and underscores the importance of comprehensive molecular analyses in patients with complex phenotypes.

THE ROLE OF IMMUNOINFLAMMATORY MARKERS IN THE PROGNOSIS AND RESECTABILITY OF PANCREATIC ADENOCARCINOMA.

BACKGROUND: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. AIM: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. METHODS: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. RESULTS: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). CONCLUSIONS: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

The role of immunoinflammatory markers in the prognosis and resectability of pancreatic adenocarcinoma / O papel dos marcadores imunoinflamatórios no prognóstico e ressecabilidade do adenocarcinoma pancreático

ABSTRACT Background: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. Aim: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. Methods: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. Results: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). Conclusions: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

RESUMO Racional: O adenocarcinoma pancreático apresenta alta taxa de mortalidade. Uma ferramenta que possa predizer adequadamente o seu prognóstico é fundamental para melhor estratificação de risco. A razão neutrófilos/linfócitos e suas adaptações e a razão plaquetas/linfócitos tem se mostrado promissores para este fim. Objetivo: Avaliar o valor prognóstico das razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos, analisar os pontos de corte mais adequados e investigar sua utilidade como fator preditivo de ressecabilidade. Métodos: Foram coletados dados de pacientes com adenocarcinoma pancreático atendidos no Hospital de Clínicas de Porto Alegre entre 2003 e 2013. As razões estudadas foram determinadas com base nos hemogramas coletados na internação e após dois ciclos de quimioterapia paliativa. Resultados: As razões neutrófilos/linfócitos basal, neutrófilos/linfócitos derivada basal e plaquetas/linfócitos basal não tiveram impacto prognóstico na sobrevida (p=0,394, p=0,152, p=0,177 respectivamente). No subgrupo submetido a quimioterapia paliativa, as razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos após dois ciclos de tratamento mostraram-se fatores prognósticos para sobrevida global (p=0,003, p=0,009 e p=0,001 respectivamente). Os pontos de corte encontrados foram 4,11 para neutrófilos/linfócitos (sensibilidade 83% e especificidade 75%), 362 para plaquetas/linfócitos (sensibilidade 91% e especificidade 62,5%) e 2,8 para neutrófilos/linfócitos derivada (sensibilidade 87% e especificidade 62,5%). As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos não se mostraram estatisticamente significativas como preditores para ressecabilidade (p=0,88; p=0,99 e p=0,64 respectivamente). Conclusões: As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos são úteis como marcadores prognósticos de sobrevida global em pacientes com adenocarcinoma pancreático submetidos à quimioterapia paliativa. Seu uso como preditor de ressecabilidade não foi demonstrado.

Perioperative synbiotics decrease postoperative complications in periampullary neoplasms: a randomized, double-blind clinical trial.

Periampullary neoplasms are rapidly progressive tumors with a poor prognosis and high morbidity and mortality rates, which have a negative influence on patient outcomes. Some probiotics and prebiotics have the ability to protect the intestinal barrier and prevent bacterial translocation, infection, and postoperative complications. We evaluated the use of synbiotics in a prospective, double-blind study of patients undergoing surgery for periampullary neoplasms (PNs) and assessed the effect of these agents on nutritional status, postoperative complications, antibiotic use, length of hospital stay, and mortality. Patients were randomized to receive probiotics and prebiotics-synbiotics--group S [Lactobacillus acidophilus 10, 1 × 10(9)CFU, Lactobacillus rhamnosus HS 111, 1 × 10(9) CFU, Lactobacillus casei 10, 1 × 10(9) CFU, Bifidobacterium bifidum, 1 × 10(9)CFU, and fructooligosaccharides (FOS) 100 mg]--or placebo-controls--group C, twice daily, for a total of 14 days. Risk, clinical status, and postoperative complication rates were assessed. Twenty-three patients were allocated to each group. The incidence of postoperative infection was significantly lower in group S (6 of 23 patients, 26.1%) than in group C (16 of 23 patients, 69.6%) (P = 0.00). Duration of antibiotic therapy was also shorter in group S (mean = 9 days vs. 15 days in group C; P = 0.01). Noninfectious complications were less common in group S (6 of 23 vs. 14 of 23 patients in group C; P = 0.03). Mean length of hospital stay was 12 ± 5 days in group S vs. 23 ± 14 days in group C (P = 0.00). No deaths occurred in group S, whereas 6 deaths occurred in group C (P = 0.02). Perioperative administration of synbiotics reduces postoperative mortality and complication rates in patients undergoing surgery for PNs.

Ressecções pancreáticas: experiência do grupo de vias biliares e pâncreas do Hospital de Clínicas de Porto Alegre entre 2000 e 2003 / Pancreatic resections: experience of the pancreato-biliary group at Hospital de Clínicas de Porto Alegre, Brazil, between 2000 and 2003

Este trabalho apresenta a experiência de 20 ressecções pancreáticas e tem como objetivo principal ressaltar a importância dos centros de referência para doenças de tratamento cirúrgico complexo, como é o caso dos portadores de neoplasia da confluência biliopancreática. De 60 doentes com neoplasia biliopancreática tratados no período de janeiro de 2000 a janeiro de 2003, 20 foram submetidos a ressecção: 16 a duodenopancreatectomia, três a ressecção corpo-caudal e um a ressecção da Papila de Vater. As complicações mais freqüentes foram: cinco fístulas pancreáticas, sete abscessos intra-abdominais e oito infecções do aparelho respiratório. A mortalidade foi de 0 por cento. Nos Estados Unidos, em hospitais com pequena experiência, nos anos de 1984 a 1991, a mortalidade foi de 21,8 por cento; já em centros de referência, foi de 4 por cento. Em série anterior do Hospital de Clínicas de Porto Alegre, referente ao período de 1988 a 1999, a mortalidade foi de 20 por cento. A presente série confirma a experiência internacional: o resultado das ressecções pancreáticas é melhor em centros de referência. A indicação da cirurgia, os cuidados pré e pós-operatórios e a experiência de uma equipe que realiza o procedimento no mínimo de 10 a 15 vezes por ano são fundamentais para a obtenção de bons resultados, com a gradativa diminuição do tempo de internação e dos custos hospitalares

Digital karyometry in pancreatic adenocarcinoma.

OBJECTIVE: To characterize nuclei from pancreatic adenocarcinoma and nonneoplastic pancreatic tissue by digital karyometry, demonstrating specific nuclear signatures for each of them. STUDY DESIGN: Of cells from malignant and nonmalignant pancreatic tissue, 1,300 nuclei were assessed by digital karyometry from paraffin blocks stored at the Pathology Service of Hospital de Clinicas de Porto Alegre. A set of 40 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus. Signatures were created for both types of tissue, and a distance metric from "normal" was defined and calculated for them. RESULTS: There were significant differences in 11 features between the 2 groups, allowing the creation of digital signatures. CONCLUSION: Nuclear chromatin texture signature can offer a specific digital characterization for both pancreatic adenocarcinoma and nonmalignant pancreatic tissue. Several isolated nuclear features serve as markers for the diagnosis of pancreatic adenocarcinoma. The present karyometric study of normal and malignant pancreatic tissue may be of use as a continuing tool to early diagnosis of pancreatic adenocarcinoma as it can be applied to cytologic specimens, also. In the future, studies using this technique should assess the chemopreventive potential of different agents as well as prognosis and treatment options for pancreatic adenocarcinoma.

Cirurgia videolaparoscópica nas doenças biliopancreáticas / Laparoscopic surgery in pancreatobiliary diseases

Com a experiência adquirida na cirurgia da vesícula biliar, a videocirurgia está sendo indicada cada vez mais em outras doenças. Decorridos 15 anos da primeira cirurgia, os autores avaliam os resultados e analisam as perspectivas deste procedimento nas doenças biliopancreáticas. Seguem a proposta que divide este procedimento em procedimentos de rotina, avaliação e desenvolvimento. Nas doenças da vesícula biliar, a colecistectomia laparoscópica é considerada padrão ouro, levando vantagem em todos os itens sobre a laparotômica, excluídas as lesões da via biliar e o vazamento biliar pelo coto cístico. Enfatizam situaçõesespeciais: da colecistite aguda, da colecistectomia durante a gravidez, da vesícula em porcelana e do câncerda vesícula. Comentam as perspectivas da videocirurgia nas complicações da colecistectomia laparoscópica. No tratamento da coledocolitíase, consideram o procedimento como em avaliação pela falta de ensaios clínicos prospectivos randomizados com grupo controle comparáveis e acompanhados por prazo de tempo maior. Nas doenças do pâncreas, a videocirurgia é um procedimento em desenvolvimento, com exceção da pancreatite aguda biliar não complicada, que se beneficia com a colecistectomia laparoscópica. O mesmoocorre com as cirurgias de derivação para desobstrução da via biliar. Embora factíveis dentro dos princípios da cirurgia convencional, faltam estudos comparativos com outras técnicas existentes analisando eficácia e efetividade.

With the acquired experience with laparoscopic cholecystectomy, videosurgery has been used more andmore for treatment of other diseases. Since the first surgery, nearly 15 years ago, the authors evaluate the outcome and the perspectives of this procedure in pancreatic-billiary diseases. They followed the proposition which divides these procedures in routine procedures, in evaluation and in development. In gallbladder diseases the laparoscopic cholecystectomy is considered gold-standard, taking advantage upon opencholecystectomy, excluding bile duct injury and cystic stump leakage. They emphasize the aspects related to acute cholecystitis, cholecystectomy during pregnancy, calcified gallbladder and cancer. The laparoscopic cholecystectomy during pregnancy is considered as a procedure in evaluation. Long term effects of pneumoperitonium on foetus are not well known. The approach in calcified gallbladder, because the high incidence of adenocarcinoma, remains questionable. Perspectives of videosurgery in complications of laparoscopic cholecystectomy are commented. Cystic stump leakage, misplaced clips and partial section or laceration of main biliary tract could be treated by new videosurgery in selected situations. In the treatment of choledocolithiasis, they consider the procedure as one for evaluation, due to the lack ofrandomized prospective trials. Until now, videocholedocolitotomy is reserved to specialized centers. Inpancreatic diseases, videosurgery is a procedure in development, except for the non-complicated acute biliary pancreatitis, in which benefits with laparoscopic cholecystectomy has been shown. The same occurs with diversion surgeries for desobstruction of the biliary tree. Although performed within the conventional surgery principles there is a lack of comparative studies with other techniques analysingefficacy and efficiency.

Associaçao entre doença coronariana e pregas no lobo da orelha (PLO) / Association between coronary disease and ear lobe creases (ELC)

Este artigo de revisao comenta inicialmente o papel da prega no lobo da orelha (PLO) na seleçao de pacientes com maior risco para acidentes coronarianos. Em seguida, detém-se na apresentaçao das evidências da associaçao entre esses dois achados. Finalmente, concluindo-se que a PLO deve ser valorizada na identificaçao dos indivíduos com doença coronariana, principalmente pela simplicidade deste exame

Cistos hepaticos nao parasitarios / Nonparasitic cystic liver disease

Os cistos hepaticos nao parasitarios constituem uma afeccao rara para a qual nao exsite um consenso quanto a forma de classificacao e tratamento. Os autores realizam uma revisao da literatura enfocando principalmente a abordagem diagnostica e terapeutica. Evidenciam uma maior frequencia de diagnostico devido a melhor qualidade e maior disponibilidade dos modernos metodos de imagem. Alem das formas tradicionais e discutido o uso da cirurgia videolaparascopica como um novo metodo de tratamento