Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis.

Bacterial translocation is an important source of pancreas infection in acute pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis has been proved in various studies. The aim of this study was to determine whether potent PAF antagonists influence bacterial translocation in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats treated with PAF factor antagonists received intravenous injection of WEB-2170 (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before induction of acute pancreatitis. Six hours after induction of acute pancreatitis, bacteriologic cultures and histologic scoring of tissues were performed. There was a statistically significant reduction in bacterial translocation to the mesenteric lymph nodes and liver but not to the pancreas of the rats treated with PAF antagonists. No significant increase in the intestinal bacterial population of any group was found. There were no statistical differences between the pancreatic histologic scores of the groups. PAF antagonists reduced bacterial translocation to distant sites other than the pancreas, preventing the bacterial dissemination that occurs in the early phase of acute pancreatitis and may have beneficial effects on the evolution of this disease.

New technique of pancreaticojejunal anastomosis after partial pancreaticoduodenectomy.

The authors propose a new technique of pancreaticojejunal anastomosis after pancreatoduodenectomy with the aim of reducing the incidence of anastomotic disruption and late stenosis of the duct. Basically the technique consists of end-to-end pancreaticojejunal anastomosis with invagination of the pancreas into the intestinal loop and mucosal juxtaposition of the pancreatic duct and jejunum.

A new technique of gastroenterostomy for palliative treatment of pancreatic head carcinoma.

BACKGROUND/AIMS: Most of the patients with pancreatic cancer can be only palliatively treated. Although 30% of the patients submitted to palliative biliary bypass will require further treatment for duodenal obstruction, prophylactic gastric bypass still remains a controversial issue in the management of unresectable pancreatic head carcinoma. The main disadvantage of current techniques of gastrojejunostomy is postoperative vomiting due to impaired gastric motility and circulus vitiosus through the nonobstructed duodenum. A new technique of prophylactic gastrojejunostomy is described herein as an attempt to obviate these complications. METHODOLOGY: An antecolic isoperistaltic gastrojejunostomy was fashioned at the gastric mid-body above the angulus. The afferent limb was partitioned close to the gastrojejunostomy and a Braun type entero-enterostomy constructed joining the afferent and the efferent limbs. Following the gastrojejunostomy a Roux-en-Y choledochojejunostomy was performed. RESULTS: In 19 patients consecutively submitted to this procedure no postoperative mortality or complications occurred. Nasogastric suction was interrupted at postoperative day 3 and oral feeding resumed on the next day. Neither early nor late postoperative vomiting was observed. CONCLUSIONS: These encouraging preliminary results suggest that this procedure may have its place in the palliative treatment of pancreatic head carcinoma.

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.

Pancreatic head tumors with portal vein involvement: an alternative surgical approach.

BACKGROUND/AIMS: One of the determining factors for the unresectability of pancreatic head tumors is the involvement of the portal venous system. Recent reports show that the resection of tumors with portal vein involvement has similar results to lesions with same stage without portal vein invasion. The aim of this study is to present a technique that allows the resection of portal vein segments without the use of grafts and with a shorter period of intraoperative venous occlusion. METHODOLOGY: Fifteen patients with pancreatic head tumors and portal vein involvement were submitted to pancreaticoduodenectomy according to this technique. The main feature of the technique is starting the pancreatic dissection at the posterior aspect of the head of the pancreas. The superior mesenteric artery is completely dissected from the pancreatic tissues leaving the section of the pancreas and the resection of the portal vein to the last step. RESULTS: Portal vein flow occlusion did not exceed 10 minutes. There were no major postoperative complications or mortality. CONCLUSIONS: This maneuver allows an easier resection of the mobilized portal vein with a shorter period of venous clamping and reconstruction without the need of venous graft.

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.

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.

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.

Management of pancreatic pseudocysts in chronic alcoholic pancreatitis with duct dilatation.

Twenty-one patients with pancreatic pseudocysts secondary to alcoholic pancreatitis were treated by cystojejunostomy (16), cystoduodenostomy (4) and external drainage (1). In all patients, the duct of Wirsung was drained into a defunctionalized loop of the jejunum at the same operation. There was no early or late mortality. Pseudocyst recurrence did not occur, and only one patient (4.7%) had light pain recurrence in the follow-up period. The importance of providing an outflow route for the obstructed pancreatic duct, and not just for the pseudocyst, is stressed due to this experience with patients affected by underlying chronic pancreatitis.

Surgical treatment of biliary complications from calcifying chronic pancreatitis.

Obstructive jaundice in patients with chronic pancreatitis still constitutes a surgical problem deserving the attention of many specialized centers throughout the world. Out of a series of 149 patients operated upon for chronic pancreatitis, 45 (30.2%) with common duct stricture secondary to pancreatic disease have been studied in this series. Eleven patients (24.4%) had transient jaundice, eleven (24.4%) persistent cholestasis and six patients (13.3%) presented cholestasis with cholangitis. Seventeen patients (37.7%) were considered to have asymptomatic biliary tract stenosis. In 37 patients, pancreatic and biliary tract surgery were performed at the same time. There were two postoperative deaths (4.4%) and the late mortality was 9.3%. Choledochojejunostomy was preferred in the treatment of biliary stricture associated with pancreatitis. Cholecystojejunostomy provides inadequate biliary decompression and should not be used in the treatment of these patients. When a pancreatojejunostomy needs to be performed in association with biliary tract decompression, a double intestinal loop technique should be used because it is associated with less morbidity and mortality.

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.

[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.

[Surgical treatment of solitary liver cysts]. / Tratamento cirúrgico do cisto solitário de fígado.

Solitary hepatic cysts an uncommon disease in the past, which incidental diagnosis is increasing with the advent of ultrasound and computed tomography, are nowadays very frequent. Cysts that reach massive proportions often become symptomatic and necessitate surgical intervention. Surgical wide unroofing technique is a simple procedure advocated for the treatment of symptomatic patients. Ten patients with solitary liver cysts were submitted to wide unroofing with good immediate and late results.

[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.

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension.

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.

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.

Clinical and pathologic prognostic factors for curative resection for pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related deaths in the world. Operative resection is the only therapeutic option with curative potential for this disease. OBJECTIVE: The aim of the present study was to correlate clinical and pathologic parameters with survival in patients submitted to pancreatic resection for pancreatic adenocarcinoma. METHODS: Surgical resection with curative intent (R0 and R1 resections) was performed in 65 pancreatic cancer patients between 1990 and 2006. The overall results of surgical treatment were retrospectively analyzed and compared with the clinicopathologic features of these patients. RESULTS: Pylorus-preserving pancreatoduodenectomy was performed in 37 patients (56.9%), classic resection in 35.4%, distal pancreatectomy in 4.6% and total pancreatectomy in 3.6%. The inhospital mortality was 5% (three patients). Postoperative complications occurred in 28 patients (43%). Mean survival and five-year survival rate after curative resection were 27 months and 9.0%, respectively. Sex, TNM stage, tumor differentiation, neural invasion, tumor size and involvement of resection margin were significant prognostic factors on univariate analysis. Multivariate analysis showed tumor differentiation and neural invasion as prognostic factors. CONCLUSION: Patients with pancreatic cancer, even those with poor prognostic factors should be given the opportunity of surgical resection with curative intent.

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.