Revising the M235T polymorphism position for the AGT gene and reporting a modifying variant in the Brazilian population with potential cardiac and neural impact.

There is a growing need to curate the overwhelming amount of sequencing data which is available in many public databases. For instance, new information shows that the M235T polymorphism at the angiotensinogen gene (AGT) is actually positioned at the position corresponding to the amino acid 268 and not 235. This polymorphism is filled as rs699 in the NCBI SNP database and results in the synthesis of a threonine (T) instead of a methionine (M). It has been widely studied and associated as an important risk factor for several vascular and neuropsychiatric conditions. We faced this new situation during the targeted sequencing of 360 chromosomes from Brazilian subjects studied for the M235T polymorphism, leading to the identification of a novel variation (rs141900991). This report explores the potential impact of such a dinucleotide variation, which promotes the change of alanine (A) to serine (S) at the AGT protein structure (A237S). Considering the previous M268T variation at the four possible haplotypes combined (MA, MS, TA and TS), we performed a comparative hydrophobicity simulation, using the Kyte-Doolittle algorithm, available at the CLB Bio workbench, in the four possible haplotypes. Additional simulations were performed using the programs PolyPhen, I-Mutant and SIFT, in order to evaluate the pathogenicity of both mutations. The predicted hydrophobicity decreases of a similar magnitude, with both MS and TA haplotypes, but the presence of both variations induces a major decrease in hydrophobicity, suggesting a cumulative effect, with possible modifying effect since that this variation per se would limit the hydrophobicity range and the latter chances in finding significant phenotype differences. A better characterization of this kind of variant is particularly important because the current genome wide scan analyses in complex disorders with cardiac or neural etiology are not generating reliable findings, especially if we consider the huge investment with such approach. Additional and unknown variations like this one, with potential modifying effect, might be more common than previously expected.

Insulinoma: diagnostic strategies and surgical treatment. A 22-year experience.

BACKGROUND/AIMS: The efficacy of preoperative localization methods and the results of the surgical treatment of insulinoma were studied. METHODOLOGY: Fifty-nine patients referred for surgical treatment were studied and the results of the diagnostic tools for tumor localization were compared with findings at surgical intervention. The influence of the type of surgical procedure in the immediate and late postoperative course was also studied. RESULTS: Ultrasonography had a sensitivity of 30%, computed tomography 25%, angiography 54%, portal vein sampling 94%, endoscopic ultrasonography 27% and magnetic resonance 17%. Intraoperative palpation localized 98.2% of the tumors and by the addition of intraoperative echography, all lesions were identified. In 55 patients with benign lesions, 22 enucleations, 25 distal pancreatectomies, 7 pancreatectomies plus enucleation and one duodenopancreatectomy were performed. Malignant tumors were treated by pancreatic resection, postoperative hepatic artery embolization and systemic chemotherapy. There was no postoperative mortality. Pancreatic fistula was the most common complication. Three patients who underwent distal pancreatectomy developed late diabetes (9.3%). CONCLUSIONS: Extensive preoperative investigation, mainly with invasive methods, is not indicated and by combining intraoperative palpation and echography most of the cases can be adequately dealt with. Preservation of pancreatic tissue with enucleation and preservation of the spleen are the best choice for treatment of benign insulinomas.

Distal pancreatectomy without splenectomy and with preservation of splenic vessels.

BACKGROUND/AIMS: Conventional distal pancreatic resection routinely involves splenectomy. The awareness that spleen removal may lead to postoperative septic and hematological complications motivated the development of spleen-preserving procedures. Successful distal pancreatectomy with splenic conservation has been reported for treatment of benign pancreatic diseases of the distal pancreas. This report presents the results of spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein. METHODOLOGY: Ten patients underwent distal pancreatectomy with splenic vessel preservation. In all cases, both splenic vessels were separated from the pancreas towards the spleen after transecting the body of the pancreas. RESULTS: The indications for the procedure were: neuroendocrine pancreatic tumors (n = 4), cystic neoplasm of the pancreas (n = 4) and cystic-papillary pancreatic tumors (n = 2). Four patients developed pancreatic fistulas with spontaneous healing and there was no mortality. CONCLUSIONS: Spleen-preserving distal pancreatectomy with splenic vessel conservation can be safely performed and should be indicated in the surgical management of benign pancreatic diseases of the distal pancreas.

Surgical treatment of cicatricial biliary strictures.

BACKGROUND/AIMS: Cicatricial biliary strictures are usually associated with high morbidity and mortality rates, frequently related to technical difficulties of their surgical repair, mainly in hilar lesions. Interference with bile duct blood supply during surgical attempts for correction is a major factor for unsuccessful results. The aim of this study is to evaluate, after an extended follow-up period, the results obtained with a modified technique for surgical correction of cicatricial biliary strictures. METHODOLOGY: The medical records of 57 patients surgically treated for cicatricial biliary strictures between January 1984 and July 1995 were reviewed and the immediate and long term results retrospectively analyzed. Patients consisted of 46 females and 11 males. The average age was 43 years. The etiology of the biliary lesion was: cholecystectomy alone (23); cholecystectomy with duct exploration (8); T tube CBD drainage (6); Biliary-enteric anastomosis stricture (16); choledochoplasty (2) and trauma (2). In 28 cases (49.1%) the stricture was located in the upper third of the bile duct, in 28 (49.1%) in the middle third and in one case (1.7%) it was low. All patients were submitted to longitudinal Roux-en-Y hepaticojejunostomy with mucosa apposition after dissection of the anterior aspect of the biliary tract. No transanastomotic stents were used. RESULTS: Ten patients (17.5%) presented 11 postoperative complications: biliary fistula (4), duodenal fistula (1), wound infection (5), and acute pancreatitis (1). Average hospital stay was 11 days and there were no postoperative mortalities. The follow-up study was possible in 54 patients and ranged from one to ten years, with an average of 2.9 years. Four patients of 28 (14%) with hilar lesions developed stricture recurrence and cholangitis episodes, whereas no patients bearing lesions below the biliary junction had such complications. CONCLUSION: Roux-en-Y hepaticojejunostomy with mucosa apposition without transanastomotic stent performed after minimal dissection of the biliary duct, thus avoiding major interference with the bile duct blood supply, is a safe and efficient method for the surgical repair of cicatricial biliary strictures. Using this technique excellent results can be obtained in the lesions below the biliary junction and acceptable results may be achieved in patients with hilar lesions.

[Surgical treatment of insulinoma: study of 59 cases]. / Tratamento cirúrgico dos insulinomas--Estudo de 59 casos.

UNLABELLED: After establishing the diagnosis of an insulinoma the next step is its localization in order to perform the most suitable management approach. PURPOSE: To evaluate the methods used for the diagnosis of insulinoma and the localization of its site as well as the results of the surgical treatment. METHODS: Fifty nine consecutive patients with pancreatic insulinomas were studied. The discriminative power of the preoperative investigations in the localization of insulinomas was analysed. Special attention was focused to the intra operative methods of tumor localizations. The early and late results of the surgical treatment were also investigated. RESULTS: There were 55 benign cases and 4 malignant tumors. Preoperative localization was attempted by using ultrasonography (positive in 28.1%) CT imaging (positive in 25%), selective arteriography (positive in 54.1%), endoscopic ultrasonography (positive in 27.2%) and assay of portal plasma insulin levels (positive in 94.4%). In 54/55 cases (98.2%) the tumors were identified intraoperatively by palpation. By addition of intraoperative ultrasonography all lesions were identified and successfully removed without mortality. Five patients had multiple endocrine neoplasias all with multiple lesions in the pancreas. In patients with benign lesions 29 enucleations and 32 resections were performed. Pancreatic fistulas were the most common complication (29/59). Excluding the patients with malignant lesions the recovery rate was 98.1%. Three patients who underwent corporo caudal pancreactectomy developed diabetes. CONCLUSIONS: The preoperative localization is not necessary, since a combination of palpation and intraoperative ultrasonography can deal with most cases. Enucleation when possible is the best choice for benign lesions.

Pyogenic liver abscess: the role of surgical treatment.

MATERIALS AND METHODS: We present an analysis of 48 patients with pyogenic liver abscess (PLA) that were treated according to a protocol between 1975 and 1993. In this period, 35 patients with PLA were treated by surgical drainage (SD). The indication for surgical treatment of the abscess were patients in septic conditions, underlying intra-abdominal surgical disease and the failure/contraindication of other therapeutic methods. Thirty-one patients were submitted to surgical treatment as the initial procedure and four patients unsuccessfully treated by percutaneous drainage, underwent SD. RESULTS: The surgical approach was indicated in patients with severe disease and presented 91.5% of good results, and a mortality rate of 8.5%. CONCLUSIONS: These results suggest that surgical treatment is a good alternative as a first step not only for the treatment of the primary cause of the abscess but also in septic patients with severe disease where a delay in adequate drainage, frequent in percutaneous management, can lead to high morbidity and mortality rates.

[Biliary fistula after elective conventional cholecystectomy]. / Fístula biliar após colecistectomias convencionais eletivas.

The use or not of drainage after elective cholecystectomy has been recently studied, and we will discuss the real incidence of the subhepatic biliary collection and its clinical significance. In this sense, we studied 20 patients with a mean age of 45 years (4 male and 16 female), submitted to elective cholecystectomy according to selective techniques patterned by our group, where we realized ligature of all vessels of the gallbladder bed, and subhepatic drainage. These patients receibed 99 mTc-DISIDA at the moment we closed the abdomen, and in a period of 24 and 48 hours we studied its presence in the subhepatic bed and in the drainage material. All the patients had not post-operative complications and none biliary drainage or subhepatic collection scanned. We concluded that using our preconized techniques, the subhepatic drainage is unnecessary after elective cholecystectomy.

[Results of conventional cholecystectomy. Experience in a university hospital]. / Resultados da colecistectomia convencional. Experiência em hospital universitário.

The experience with open cholecystectomy in an university affiliated hospital is documented in this report. We studied retrospectively 221 patients operated between 1987 and 1992, type of surgery, morbidity and mortality were analyzed. There were 171 (77.3%) cholecystectomy alone and 50 (22.7%) cholecystectomy with other biliary surgery (BS). Pulmonary, urinary and wound complications were the most common. Overall incidence of complications was 7.2%. For patients with cholecystectomy alone morbidity was 3.5% and for patients with BS morbidity was 20% (p < 0.002). There were no mortality in this group of patients.

[Distal pancreatectomy with conservation of the spleen]. / Pancreatectomia corpo-caudal com preservação de baço.

Conventional resection of the body and tail of the pancreas usually involves splenectomy. There are evidence that spleen removal can lead to septic and hematological complications and should, therefore, be avoided when possible. Distal pancreatectomy with spleen conservation has been described by specialized centers with good results. This report describes our experience in 8 cases with conservation of the spleen during the resection of the body and tail of the pancreas. The technique has been applied in patients with pancreatic neuroendocrine tumors (n = 4), cystic tumors (n = 3) and cystic-papillary tumor (n = 1) with no complications and good late results in all cases.

[Effect of omeprazole administration on pancreatic content of enzymes in rats]. / Efeito da administração de omeprazol sobre o conteúdo pancreático de enzimas em ratos.

Gastric chloride acid plays an important role in pancreatic enzyme synthesis and secretion, mediated by cholecystokinin released in the duodenum. This study was designed to evaluate the influence of gastric acid suppression by omeprazole on pancreatic enzyme content. Eighteen male Wistar rats (180-220 g) were divided in two groups: I--control and II--omeprazole. Animals received by intraduodenal catheter 3 doses of 0.5 ml saline solution (NaCl 0.9%)--Group I or 5 mumol/Kg of omeprazole solution--Group II at 24 h intervals. All animals, after an overnight fasting period, were killed 3 h after the last dose. Serum amylase and pancreatic tissue content of protein, trypsinogen, elastase, lipase and phospholipase A2 were determinated. Omeprazole treated animals (group II) showed statistically significant lower levels of serum amylase and pancreatic trypsinogen content (P < 0.05). We believe that this effect is related with acid secretion suppression by omeprazole and that it may be mediated by cholecystokinin.

Surgical treatment of pancreatic ascites and pancreatic pleural effusions.

BACKGROUND/AIMS: Massive ascites and pleural effusions are uncommon but well-documented complications of chronic pancreatitis. The present study reviews the results of surgical management of pancreatic ascites and pleural effusions of pancreatic origin. PATIENTS AND MATERIALS: From forty-nine patients with chronic pancreatitis presenting with ascites and/or pleural effusion of pancreatic origin, 31 were surgically treated. RESULTS: Nineteen had ascites only, ten pleural effusions and two presented with both conditions. Diagnosis of the internal pancreatic fistula was based on the findings of high amylase levels and elevated albumin content of the peritoneal and pleural exudates. Failure of medical therapy was the indication of surgical treatment in all patients. Thirteen were submitted to internal pancreatic drainage, 17 to external drainage and one to distal pancreatic resection. Eight of 17 externally drained patients were reoperated for intraperitoneal abscesses (2), infected pseudocyst (1), pain recurrence (3) and pancreatic fistula (2); whereas reoperation occurred in only one of the 13 patients submitted to internal drainage (p < 0.05). CONCLUSIONS: Internal pancreatic drainage was the ideal surgical treatment for patients with pancreatic ascites and/or pleural effusion that did not respond to medical treatment. When this was not feasible external drainage was successfully used as an alternative to pancreatic resection.

[Prognostic value of the sites of pancreatic necrosis determined by computed tomography of the abdomen]. / Valor prognóstico das localizações das necroses pancreéaticas pela tomografia computadorizada de abdome.

Correlations between tomographic findings and the outcome of the disease was made in 49 patients with necrotizing pancreatitis submitted to surgical treatment. Mortality rate was 20.40% resulting mostly from sepsis and multiple organ failures. There was no correlation between APACHE II index and number of necrotic areas diagnosed by abdominal computed tomography although they were closely related with mortality. These findings suggest that different necrotic areas have different prognostic values. The root of the superior mesenteric artery and retropancreatic area were related to worst prognosis with 100% mortality rate. Incomplete necrotic tissue removal is the possible explanation for the high mortality rate.

[Pyogenic hepatic abscess: report of 51 cases]. / Abscesso hepático piogênico: análise de 51 casos.

Pyogenic hepatic abscesses are uncommon. We report our findings in 51 patients with pyogenic liver abscess treated from 1975 through 1992. Twenty-eight patients were men and twenty-three were women. The median age of patients was 46 years (range, 13 to 77 years). Fever was present in 100% of patients, abdominal pain in 58.8% and jaundice in 39.2%. Twenty eight patients (54.9%) had leukocytosis; 45% hyperbilirrubinemia and 35.3% a high serum level of alkaline phosphatase. The most common cause of abscesses was biliary tract disease (66%). Thirty-three (64.7%) were surgically treated and thirteen underwent percutaneous drainage with 90.4% and 69.2% of good results, respectively. Mortality was 9.6% in the surgical group and 0% in the percutaneously drained group. A review of literature of this condition and a discussion about the diagnosis, treatment and etiopathogenesis are presented.

[Acute pancreatitis: a clinically based classification]. / Pancreatite aguda: uma classificação com base clínica.

Acute pancreatitis is a protean disease characterized by wide clinical variation and many pathological alterations. This variability in presentation and clinical course has plagued the study and management of the disease. The lack of accepted definitions for acute pancreatitis and its complications has led to difficulties in devising a clinical classification system useful for case management. An attempt in this direction was made by a diverse group of 40 international authorities from six medical disciplines and 15 countries, joining a Symposium in Atlanta, Ga, in September 1992. From this meeting resulted a clinically based classification system for acute pancreatitis valuable to practicing clinicians and to specialists seeking to compare inter institutional data.

[Lymphoma of the biliary tract: report of 2 cases]. / Linfoma das vias biliares: relato de dois casos.

We report two cases one a primary non Hodgkin lymphoma of the hepatic common duct and the other a secondary involvement of the biliary tract in a patient with a Hodgkin's disease. In the first case a local resection of the biliary lymphoma was undertaken being the patient alive six months after the procedure. The second case died early after the operative biliary external drainage in a septic shock before any specific treatment could be initiated.

[Duodenal ulcer clinically simulating pancreatic neoplasm]. / Ulcera duodenal simulando clinicamente o câncer de pâncreas.

A small fraction of solid mass in the head of the pancreas are inflammatory rather neoplastic in origin. The failure to recognize the true nature of a solid tumor in the head of pancreas may lead to an incorrect treatment strategy. This is a report of a patient with clinical history of pancreatic cancer which computed tomography showed a mass in the head of the pancreas with radiologic characteristics of malignancy. The patient underwent exploratory laparotomy with the finding of a mass in the head of the pancreas. The inflammatory palpable characteristic of the mass led to a intraoperative biopsy to confirm the preoperative diagnosis. With the benign result of the biopsy, the final diagnosis was duodenal ulcer which penetrates in the pancreatic parenchyma.

[Cavity effusions in patients with chronic pancreatitis]. / Derrames cavitários em portadores de pancreatite crônica.

In Brazil, the incidence of IPF due to alcohol-induced CP seems to be higher than in other countries. The authors analysed some general, epidemiologic, laboratory and radiologic features in 98 patients with CP, all of them alcoholics, divided in two groups: 49 patients without IPF (I) and 49 patients with IPF (II). The authors first analysed the following parameters in each group and then comparatively in both groups: age, sex, race, smokers and daily consumption of cigarettes, daily consumption of alcoholic beverages, years of alcohol consumption, and mortality. The authors concluded that pancreatic fistula plays in effusions the main role, secondary to cysts disruption or necrosis of the main pancreatic duct.

[Duodenal perforation following endoscopic papillotomy: report of 3 cases]. / Perfuração duodenal pós-papilotomia endoscópica: relato de três casos.

Duodenal perforation is a rare complication of endoscopic sphincterotomy and its treatment is controversial. The authors report three cases of duodenal perforation by endoscopic sphincterotomy. In two cases with history of a previous biliary infection, surgical treatment had to been performed because of a peripancreatic abscess.

[Frantz's tumor (papillary epithelial and cystic neoplasms of the pancreas): report of 3 cases]. / Tumor de Frantz (neoplasia epitelial papilar e cistica do pâncreas): estudo de três casos.

Three cases of Frantz tumor, a papillary and cystic tumor of the pancreas, are discussed and compared with other cases reported in the literature. The neoplasm behaved in these three cases as a benign tumor. Pancreaticoduodenectomy was performed in one patient and distal pancreatectomy in the other two. C T scan and ultrasonography are useful for the diagnosis of these tumors. Cut surfaces show mostly well encapsulated tumors with the characteristically solid and hemorrhagic-necrotic patterns. Usually they are of a very low-grade malignancy so the complete surgical removal is the treatment of choice.

[Cholecystectomy in patients with sickle-cell anemia]. / Colecistectomia em pacientes portadores de anemia falciforme.

The surgical treatment of cholelithiasis in patients with sickle cell anemia is rather frequently followed by the operative complications. In order to study the influence of pre-operative factors and post operative complications, 31 consecutive patients distributed in two groups has been studied. In group I, all the patients have been operated by conventional procedures with 43.75% of complications. In group II, a more appropriated technique and a better metabolic control ensured a lower morbidity (6.67%). There was no pos operative death in this series. Pre operative bilirubin levels was the only condition associated with increased pos operative morbidity.