Prolactin-induced changes in protein expression in human pancreatic islets.

Ex vivo islet cell culture prior to transplantation appears as an attractive alternative for treatment of type 1 diabetes. Previous results from our laboratory have demonstrated beneficial effects of human prolactin (rhPRL) treatment on human islet primary cultures. In order to probe into the molecular events involved in the intracellular action of rhPRL in these cells, we set out to identify proteins with altered expression levels upon rhPRL cell treatment, using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS). An average of 300 different protein spots were detected, 14 of which were modified upon rhPRL treatment (p<0.01), of which 12 were successfully identified using MS and grouped according to their biological functions. In conclusion, our study provides, for the first time, information about proteins that could be critically involved in PRL's action on human pancreatic islets, and facilitate identification of new and specific targets involved in islet cell function and proliferation.

No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas transplantation: a comparative analysis.

UNLABELLED: The optimal immunosuppressive regimen for simultaneous kidney pancreas transplantation (SKPT) is still not established. We conducted a study to compare the safety and efficacy of no induction versus anti-IL-2 receptor induction protocols in SKPT recipients receiving the same maintenance regimen. METHODS: Sixty-three SKPT recipients were divided into two groups: no induction group (n = 42) and anti-IL-2 receptor induction group (n = 21). All patients were maintained on tacrolimus, mycophenolate mofetil, and prednisone. Primary endpoints were 1-year acute rejection incidence and patient and graft survivals. RESULTS: Demographic characteristics were similar between the groups. Acute rejection incidence at 1 year was equal in both groups (28.6%). Kidney and pancreas allograft survival in the no induction group were 78.6% and 76.2%, and in the anti-IL-2R induction group, 81% and 71.4%, respectively (P = NS). Patient survival was also similar: 83.3% in the no induction versus 85.7% in the anti-IL-2R induction group. Deaths due to sepsis were higher in the anti-IL-2R induction group, albeit not significantly. CONCLUSION: The use of a no-induction protocol in SKPT is safe and effective immunosuppression that also reduces transplantation costs.

Pancreas retransplantation: outcomes of 20 cases.

The objective of this paper was to evaluate our initial experience with pancreas retransplantation. From January 26, 1996 to February 2005, 285 pancreas transplantations were performed, including 20 (7%) retransplants. The causes of primary graft loss were graft thrombosis in 11 (55%, 7 venous and 4 arterial); 4 (20%) chronic rejections; 2 (10%) ischemia/reperfusion injury; 1 severe graft pancreatitis; 1 primary nonfunction; and 1 sepsis. Venous drainage was placed in the iliac vessels in 14 (70%), vena cava in 5 (25%), and portal drainage in 1. The exocrine drainage was vesical in 16 (80%) and enteric in 4 (20%). In 14 cases (70%), the primary graft was removed before and in 6 (30%) at the time of retransplantation. Immunosuppression was based on antilymphocyte induction, tacrolimus, mycophenolate mofetil, and steroids in all patients. One-year patient and graft survivals were 95% and 85%. In conclusion, pancreas retransplants were feasible with results comparable to a primary pancreas transplantation.

Influence of pancreas transplantation alone on native renal function.

Pancreas transplantation alone (PTA) has become an accepted treatment of nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus are greater than those of the surgical procedure and the posttransplant immunosuppression. As a decrease in native renal function is expected, we followed this parameter among patients who underwent PTA. From January 1997 through January 2005, we performed 69 PTA in 66 patients. All patients showed glucose hyperlability with hypoglycemic unawareness, or two or more diabetic complications as well as creatinine clearance (CrCl) > or = 45 mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and prednisone. Twenty-four hour CrCl were performed after all successful PTA. We divided patients in two groups according to the pretransplant CrCl: group 1, CrCl < or = 70 mL/min (n = 20) and group 2, CrCl > 70 mL/min (n = 25). The data were analyzed using Student's t-test (P < or = .05 was considered significant). Twenty-one patients were excluded from the analysis because of death (n = 5) or graft loss (n = 8) during the first year or follow-up shorter than 1 year (n = 8). The mean value of CrCl decreased 28.8% (85.0 +/- 31 versus 60.5 +/- 36 mL/min; P < .001). There was also a 39.3% reduction among group 1 subjects (P = .003), including 10 who displayed CrCl < or = 30 mL/min. There was also a 24.4% reduction among group 2 (P = .008), but no patient developed end-stage renal disease. In conclusion, native renal function decreased significantly after PTA, but was well tolerated among patients with CrCl > 70 mL/min. Patients with CrCl < 70 mL/min show a significant risk of worsened renal function.

Donor risk index does not predict graft survival after pancreas transplantation in Brazil.

BACKGROUND: Pancreas donor risk index (DRI) was developed by using large multicenter American data to predict the risk of adverse outcomes in pancreas transplantation based on donor and technical/logistical characteristics. AIM: The goal of this study was to evaluate the usefulness of the DRI in predicting graft survival in a Brazilian population of pancreas transplant recipients. METHOD: We conducted a retrospective analysis of the 570 procedures performed by the same surgical team between 1996 and 2011. Because of the lack of sufficient data for the calculation of DRI values, only 154 cases were studied (27%), of which 105 underwent simultaneous pancreas-kidney transplantation, 33 underwent pancreas after kidney transplantation, and 16 underwent pancreas transplantation alone. Donor cause of death was classified as cerebrovascular accident (CVA) and non-CVA. Graft origin was divided into three groups: local, if the graft was obtained in the metropolitan area of the city of São Paulo; regional, if collected in other cities of the state of São Paulo; and national, if obtained outside the state. RESULTS: Logistic regression analysis did not find a statistically significant association between DRI values and 1-year graft survival (odds ratio = 0.676; 95% confidence interval 0.152 to 3.014; P = .60). One-year graft survival calculated by the Kaplan-Meier method was 89.8% in transplants with DRI ≤ 1, 77.9% in those with 1 < DRI < 1.5, and 93.3% in those with DRI ≥ 1.5 (P = .106). CONCLUSION: The pancreas DRI model did not prove effective in predicting pancreas graft survival in a Brazilian sample of recipients.

Microencapsulation and tissue engineering as an alternative treatment of diabetes.

In the 70's, pancreatic islet transplantation arose as an attractive alternative to restore normoglycemia; however, the scarcity of donors and difficulties with allotransplants, even under immunosuppressive treatment, greatly hampered the use of this alternative. Several materials and devices have been developed to circumvent the problem of islet rejection by the recipient, but, so far, none has proved to be totally effective. A major barrier to transpose is the highly organized islet architecture and its physical and chemical setting in the pancreatic parenchyma. In order to tackle this problem, we assembled a multidisciplinary team that has been working towards setting up the Human Pancreatic Islets Unit at the Chemistry Institute of the University of São Paulo, to collect and process pancreas from human donors, upon consent, in order to produce purified, viable and functional islets to be used in transplants. Collaboration with the private enterprise has allowed access to the latest developed biomaterials for islet encapsulation and immunoisolation. Reasoning that the natural islet microenvironment should be mimicked for optimum viability and function, we set out to isolate extracellular matrix components from human pancreas, not only for analytical purposes, but also to be used as supplementary components of encapsulating materials. A protocol was designed to routinely culture different pancreatic tissues (islets, parenchyma and ducts) in the presence of several pancreatic extracellular matrix components and peptide growth factors to enrich the beta cell population in vitro before transplantation into patients. In addition to representing a therapeutic promise, this initiative is an example of productive partnership between the medical and scientific sectors of the university and private enterprises.

Anesthesia for pancreas transplantation alone or simultaneous with kidney.

Improvements in perioperative care, namely, organ preservation solutions, immunosuppression, and increased experience of surgical, anesthetic, and intensive care teams, have contributed to the success of pancreas transplantation. The objective of this study was to present data on anesthesia for pancreas transplantation alone (PTA) or simultaneous with kidney (SPKT), evaluating crystalloid, albumin and blood component infusions, graft ischemic times, and weights and ages of recipient. We evaluated patients undergoing SPKT (n=73), PTA (n=49), or SPKT with kidney living donor (n=8). Aggressive monitoring and therapy were used to avoid hypoperfusion, optimized with intravenous fluids, vasoative drugs, and correction of metabolic disturbances. Three SPKT patients were not extubated at the end of surgery. There were no other complications related to anesthesia in any patient. Although it is a high-risk surgery, PTA or SPKT is routine in our practice. Adequate perioperative care is important not only for the safety of the procedure but also for graft viability, contributing to a promising long-term treatment of insulin-dependent diabetic patients.

Enteric conversion after bladder drained pancreas transplantation experience of 14 cases.

The method of exocrine diversion in pancreas allograft continues to be controversial due to the advantages versus disadvantages of bladder versus enteric techniques. Bladder drainage (BD) exposes the patient to urological and metabolic problems that may require conversion to enteric drainage (ED). The purpose of this study was to review our initial experience of conversion from BD to ED for patients who underwent pancreas transplantation originally with bladder diversion. Among 114 pancreas transplantation performed with BD, from January 1996 to April 2003, 60 were simultaneous pancreas-kidney transplantation (SPKT), 35 were pancreas transplantation alone (PA), and 19 were pancreas after kidney transplantations (PAK). Twenty-three (20.2%) cases were excluded due to early death of the patient or the graft, yielding an analyses of 91 patients. Enteric conversion (EC) was performed in 14 (15.4%) patients with a mean follow-up of 15.7 months (range, 3-51 months) after transplantation including 8 (8.8%) SPKT, 4 (4.4%) PAK, and 2 (2.2%) PA. No surgical morbidity or mortality was observed related to EC. All patients had complete resolution of the initial problem with preservation of pancreatic function. EC represents an easy, safe procedure with low morbidity and mortality rates, representing the option of choice for patients with persistent urological or metabolic disturbances.

Glycemic control during pancreas transplantation: continous infusion versus bolus.

Pancreas transplantation is a method to restore endogenous insulin secretion in insulin-dependent diabetic patients. Because glycemia >150 mg/dL may harm pancreatic graft beta cells, early glucose control using insulin administration is recommended during transplantation. The aim of this study was to evaluate the benefits of strict glycemic control during pancreas transplantation by comparing two types of insulin and glucose administration: continuous infusion and bolus. Capillary glucose was measured every 30 minutes after anesthetic induction for pancreas transplantation alone or simultaneously with kidney transplantation. Intravenous regular insulin was administered for values >150 mg/dL or glucose for values <100 mg/dL. The following timepoints were evaluated: anesthetic induction, before pancreatic graft reperfusion, and the first 4 minutes after reperfusion. Pancreatic graft ischemia time was significantly lower in the bolus group (P <.02). Immediately after reperfusion, there was a small increase in glycemia with a decrease in subsequent measurements in both groups. No significant difference in glycemia was observed between the groups at any time. Induction values were greater than all other timepoints in both groups. Glycemic control is important; it was successfully obtained with both methods. The trend to decrease glucose after reperfusion suggest early graft function.

Proximal gastric vagotomy. A comparative study between the standard technique and the extended technique associated with denervation of the greater curvature.

Forty-six patients in the postoperative period of proximal gastric vagotomy (PGV) for duodenal ulcer (DU) were studied comparatively to verify whether the dividing of the gastroepiploic nerves (Rosati's maneuver) can reduce or not the occurrence of recurrent ulcer as it was proposed. Twenty-one patients who underwent PGV associated with Rosati's maneuver (PGV-R) were compared to 25 after standard PGV (PGV-S), according to several criteria: (1) clinical evaluation; (2) pre and postoperative basal and pentagastrin-stimulated gastric acidity; (3) postoperative basal and pentagastrin-stimulated serum pepsinogen; (4) postoperative basal and sham feeding-stimulated serum gastrin; (5) postoperative endoscopy; (6) endoscopic Congo red test. Both groups were similar (P greater than 0.05) as to age, sex, levels of preoperative gastric acidity and had a 24.4 month average follow-up (12 to 58 months). There has been no significant difference between the techniques studied as to clinical, secretory, morphological or hormonal gastric tests, although PGV-R proved more effective in reducing basal gastric acidity than PGV-S (P less than 0.05). We concluded that Rosati's maneuver does not improve the results obtained with PGV, although it provided greater reduction of basal gastric acidity than PGV-S.

Serum pepsinogen before and after proximal gastric vagotomy in duodenal ulcer treatment.

Serum pepsinogen (SP) behavior was evaluated under basal conditions and under betazole stimulation in 59 patients: 14 controls, nine unoperated duodenal ulcers (DU) and 36 DU after proximal gastric vagotomy (PGV), 14 with and 22 without recurrent ulcer. The mean follow-up of the 36 patients who underwent PGV was 38.7 months. SP was higher in unoperated DU than in the control group (p less than 0.05). After PGV in DU, there is a significant decrease of SP for both the patients with and without recurrent ulcer (p less than 0.05), being statistically similar to the control group. No difference of SP was observed between DU with and without recurrent ulcer after PGV. We concluded that SP can differentiate normal subjects from DU patients, although it is not a sensitive indicator of recurrent ulcer after PGV.

[Hepatic artery aneurysm: treatment with left hepatectomy. Report of a case]. / Aneurisma da artéria hepática: tratamento pela hepatectomia esquerda. Relato de caso.

A 71-year-old female with a rupture of left intrahepatic artery aneurysm with acute upper abdominal pain, weight loss and fever. The diagnosis was established with doppler ultrasound, contrasted abdominal computer tomography scanning and celiac and mesenteric artery angiography. Prompt recognition and left hepatectomy led to a favourable outcome.

[Hepatic hemangiomas. The importance of the image]. / Hemangiomas hepáticos. Importância da imagem.

In the authors' experience, 0.24% of the patients submitted to liver imaging (ultrasound or computerized tomography) have hemangiomas. These are shown as solid nodular lesions, mostly found by chance. Sometimes they do not appear as typical solid vascular lesions. The authors' experience and the literature are discussed. A clear and concise approach to this benign neoplasm is suggested.

[Use of the Leveen shunt in the treatment of clinically intractable ascites]. / Uso da válvula de Le Veen no tratamento da ascite clinicamente intratável.

From January 1978 to August 1987, 21 patients received a peritoneovenous shunt using the Le Veen valve (LVV). The indications criteria were the long-term diuretic therapy failure (mean time = 24.4 months) or resistence to medical therapy during hospital internment. The 21 patients underwent 36 surgeries, being 4 valve position review and 11 changes of LVV. The mean age was 51.6 years. Fifteen patients had alcoholic cirrhosis, 3 postnecrotic cirrhosis, one Budd-Chiari syndrome, one mansoni Schistosomiasis, and one malignant ascites. Ten were Child B and 9 Child C patients. Eight patients with history of previous esophageal varices bleeding (EVB) underwent endoscopic sclerotherapy (EE) before LVV implantation. Seven patients died in the early postoperative period (3 Child B and 4 Child C patients). Three patients died due to EVB and the others as consequence of hepatic failure (one), cardiac insufficiency (one), sepsis (one), and bronchopneumonia (one). The mean follow-up was 19.9 months (1-61). Early LVV occlusion occurred in 4 patients and late valve occlusion in others 4 patients. The LVV changes were done at ambulatorial preceeding. Ten patients (47.6%) died in late follow-up and in these cases death was related to the main disease course. It is concluded that: 1) LVV is a useful therapy in patients with intractable ascites, since it is not the terminal manifestations of disease; 2) early mortality is related to liver function and late mortality to main disease course; 3) ascitic patients with EVB should undergo endoscopic sclerotherapy before LVV implantation.

[Surgical treatment of portal hypertension in patients with liver cirrhosis]. / Tratamento cirúrgico da hipertensão portal em cirróticos.

Surgical options in the treatment of portal hypertension in cirrhotics are reviewed, regarding elective and emergency cases as well as the results in alcoholics and non-alcoholics. After literature review and personal experience analysis, it is concluded that endoscopic sclerotherapy should be the treatment of choice in cirrhotic patients with bleeding esophageal varices. When this fails, distal splenorenal shunt is indicated for compensated Child A and B. Regarding Child C and decompensated Child B, the choice should be a portocaval or meso caval shunts or esophageal transection with a stapler associated to splenectomy.

Prognostic value of preoperative tests in the surgical treatment of ascites with the implant of Le Veen shunts in cirrhotics.

In the period of January 1978 to October 1988, 32 Le Veen shunts (LVS) were implanted in 20 patients, out of which 16 were alcoholic cirrhotics and 4 postnecrotic cirrhotics. In the present study, we correlated preoperative laboratory data of these patients with their postoperative evolution, comparing the clinical results of patients who survived more than 30 days (13 patients = 65%) with the results of those who died within the same period (7 patients = 35%). For that matter, 14 laboratory tests were performed in order to measure the serum levels of hematocrit, hemoglobin, urea, creatinine, sodium, potassium, bilirubin, albumin, AST, ALT, alkaline phosphatase, fibrinogen, gamma GT and prothrombin activity. After statistical analysis, we observed that 6 of the 14 tests performed could be considered of prognostic value in the following decreasing order of importance: fibrinogen, alkaline phosphatase, prothrombin activity, urea, gamma GT and bilirubin. We observed that all the 7 patients who died prematurely presented 3 or more of these levels altered, when compared with standard values. Based on these data, we concluded that serum levels of fibrinogen, alkaline phosphatase, urea, gamma GT, bilirubin and activity of prothrombin proved to be important factors in determining the prognosis of immediate survival in cirrhotic patients who underwent LVS implantation. We also concluded that when 3 or more of these factors are altered, the implant of LVS is contraindicated, whatever clinical criteria for indication and contraindication were taken into account.

[Surgical treatment of ascites with Le Veen shunt in patients with alcoholic liver disease]. / Tratamento cirúrgico da ascite com o implante da válvula de Le Veen em pacientes com doença hepática alcoólica.

Studies were carried out on 16 alcoholic cirrhotics with clinically intractable ascites who underwent the implant of peritoneovenous (LeVeen) shunts. Our purpose was to find out how this group of patients responded to this kind of surgical treatment for ascites. Fifteen of these patients were male and one female, with a median age of 51.3 years. According to Child classification, 7 were Child B and 9 Child C. Thirty-three surgeries were conducted, in that 5 were performed for revision of the shunt positioning and 12 for the replacement of the valves. A total of 28 shunts were used. Postoperative immediate mortality occurred in 5 patients (4 Child C and one Child B). The median late postoperative follow-up of the 11 patients who survived was 25.8 months. We concluded that LeVeen shunt implantation is a valid palliative therapeutic resource for the treatment of ascites in alcoholic cirrhotics. The results obtained with this patient population are similar to those observed in cirrhotics who presented other etiologies. We also concluded that late mortality was not related to the implant of a LeVeen shunt but was due to the normal course of the disease.

[Immunological parameters in the differential diagnosis of ascites secondary to peritoneal carcinomatosis, hepatic cirrhosis, and congestive heart failure]. / Parâmetros imunológicos no diagnóstico differencial de ascite secundária à carcinomatose peritoneal, cirrose hepática e insuficiência cardíaca congestiva.

As a contribution to the study of ascites in patients with liver cirrhosis, congestive heart failure and peritoneal carcinomatosis evaluate in serum and ascites the concentrations of alphafetoprotein, carcinoembryonic antigen and fibronectin, they might suggest a diagnosis for the basic pathology. Forty-seven patients were studied, from whom 23 with cirrhosis, 17 peritoneal carcinomatosis and 7 with congestive heart failure. We conclude that: a) none of the tools usually employed in the analysis of ascitic fluid alone can make the base pathological process responsible for producing ascites; b) fibronectins were more useful for differential diagnosis between cirrhosis and carcinomatosis; c) alpha-fetoprotein and carcinoembryonic antigen were not useful for the definition for differential diagnosis.

[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.

[Diagnosis of hepatocellular carcinoma performed by searching for serologic tumor markers]. / O diagnóstico do carcinoma hepatocelular (CHC) realizado através da pesquisa de marcadores sorológicos tumorais.

Serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, -1 fucosidase and glutathione-S-transferase are increased in 60, 90, 75 and 64% of patients with hepatocellular carcinoma. In these patients the mean plasma fibrinogen levels is 461.78 mg/dl, while mean serum copper is 200.50 mg/dl. Serum levels of desgamma-carboxiprothrombin is over 900 mg/dl in 67% of the patients (60% of them have HB virus, mostly anti HBe positive). Forty to 95% of them have increased levels of -fetoprotein (AFP). The authors suggest that cirrhotic patients, with or without HB virus, specially those with increased AFP, should have ultrasound examination of the liver every 6 months. This method of imaging has been shown to be more sensitive than AFP (72% versus 25%) in the detection of hepatocellular carcinoma smaller than 2 cm in diameter.