Insulinoma: A retrospective study analyzing the differences between benign and malignant tumors.

BACKGROUND/OBJECTIVES: Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors. METHODS: Retrospective study of 103 patients with insulinoma treated in a tertiary center. It was analyzed demographic, clinical, laboratory, localization and histologic analysis of tumor and follow up data of subjects in order to identify differences between individuals benign and malignant disease. RESULTS: Almost all patients (87%) had a benign tumor and survival rates of 100% following pancreatic tumor surgery. Those with malignant tumors (13%) have a poor prognosis, 77% insulinoma-related deaths over a period of 1-300 months after the diagnosis with a survival rate of 24% in five years. The following factors are associated with an increased risk of malignant disease: duration of symptoms < 24 months, fasting time for the occurrence of hypoglycemia < 8 h, blood plasma insulin concentration ≥ 28 µU/mL and C-peptide ≥ 4.0 ng/mL at the glycemic nadir and tumor size ≥ 2.5 cm. CONCLUSIONS: Our data help to base the literature about these tumors, reinforcing that although insulinoma is usually a single benign and surgically treated neoplasia, the malignant one is difficult to treat. We highlight the data that help predict a malignancy behavior of tumor and suggest a long follow up after diagnosis in these cases.

Endemic and opportunistic infections in Brazilian solid organ transplant recipients.

OBJECTIVE: To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. METHODS: Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. RESULTS: From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. CONCLUSIONS: Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality.

Differential gene expression profiles of hepatocellular carcinomas associated or not with viral infection

Chronic hepatitis B (HBV) and C (HCV) virus infections are the most important factors associated with hepatocellular carcinoma (HCC), but tumor prognosis remains poor due to the lack of diagnostic biomarkers. In order to identify novel diagnostic markers and therapeutic targets, the gene expression profile associated with viral and non-viral HCC was assessed in 9 tumor samples by oligo-microarrays. The differentially expressed genes were examined using a z-score and KEGG pathway for the search of ontological biological processes. We selected a non-redundant set of 15 genes with the lowest P value for clustering samples into three groups using the non-supervised algorithm k-means. Fisher’s linear discriminant analysis was then applied in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Different transcriptional levels of genes were identified in HCC of different etiologies and from different HCC samples. When comparing HBV-HCC vs HCV-HCC, HBV-HCC/HCV-HCC vs non-viral (NV)-HCC, HBC-HCC vs NV-HCC, and HCV-HCC vs NV-HCC of the 58 non-redundant differentially expressed genes, only 6 genes (IKBKâ, CREBBP, WNT10B, PRDX6, ITGAV, and IFNAR1) were found to be associated with hepatic carcinogenesis. By combining trios, classifiers could be generated, which correctly classified 100 percent of the samples. This expression profiling may provide a useful tool for research into the pathophysiology of HCC. A detailed understanding of how these distinct genes are involved in molecular pathways is of fundamental importance to the development of effective HCC chemoprevention and treatment.

Differential gene expression profiles of hepatocellular carcinomas associated or not with viral infection.

Chronic hepatitis B (HBV) and C (HCV) virus infections are the most important factors associated with hepatocellular carcinoma (HCC), but tumor prognosis remains poor due to the lack of diagnostic biomarkers. In order to identify novel diagnostic markers and therapeutic targets, the gene expression profile associated with viral and non-viral HCC was assessed in 9 tumor samples by oligo-microarrays. The differentially expressed genes were examined using a z-score and KEGG pathway for the search of ontological biological processes. We selected a non-redundant set of 15 genes with the lowest P value for clustering samples into three groups using the non-supervised algorithm k-means. Fisher's linear discriminant analysis was then applied in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Different transcriptional levels of genes were identified in HCC of different etiologies and from different HCC samples. When comparing HBV-HCC vs HCV-HCC, HBV-HCC/HCV-HCC vs non-viral (NV)-HCC, HBC-HCC vs NV-HCC, and HCV-HCC vs NV-HCC of the 58 non-redundant differentially expressed genes, only 6 genes (IKBKbeta, CREBBP, WNT10B, PRDX6, ITGAV, and IFNAR1) were found to be associated with hepatic carcinogenesis. By combining trios, classifiers could be generated, which correctly classified 100% of the samples. This expression profiling may provide a useful tool for research into the pathophysiology of HCC. A detailed understanding of how these distinct genes are involved in molecular pathways is of fundamental importance to the development of effective HCC chemoprevention and treatment.

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil

Occult hepatitis B virus (HBV) infection has been reported among patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Our aim was to evaluate the presence of occult HBV infection in patients with HCV-related liver cirrhosis (LC) with or without HCC in São Paulo, Brazil. Serum and liver tissue samples from 50 hepatitis B surface antigen-negative patients with HCV-related LC who underwent liver transplantation at the University of São Paulo School of Medicine Hospital from 1993 to 2004 were divided into groups with LC only (N = 33) and with LC plus HCC (N = 17). HBV DNA was assayed for serum and paraffin-embedded liver tissue (tumoral and non-tumoral) using real time PCR and only 1 case with HCC had HBV DNA-positive serum. All liver samples were negative. HCV genotype 3 was detected in 17/39 (43.7 percent) cases. In conclusion, using a sensitive real time PCR directed to detect HBV variants circulating in Brazil, occult hepatitis B infection was not found among HCV-positive cirrhotic patients and was rarely found among HCV-positive HCC patients. These results are probably related to the low prevalence of HBV infection in our population. Furthermore, we have also shown that HCV genotype 3 is frequently found in Brazilian cirrhotic patients, particularly when they also have HCC. More studies involving a large number of cases should be carried out to confirm these data and to further characterize Brazilian HCV genotype isolates to elucidate genetic features that might be related to its carcinogenic potential.

Laparoscopic right hemihepatectomy for hepatolithiasis.

BACKGROUND: Liver resection is the definitive treatment for unilateral hepatolithiasis. Recently, laparoscopic major hepatectomias have become more common and are being performed in highly specialized centers. However, few laparoscopic liver resections for hepatolithiasis have been reported. Chen et al. reported two cases of laparoscopic left lobectomy for hepatolithiasis, but to our knowledge, right hepatectomy has never been reported to date. This video demonstrates technical aspects of a totally laparoscopic right hepatectomy in a patient with hepatolithiasis. METHODS: A 21-year-old woman with right-sided nonoriental primary intrahepatic stones was referred for surgical treatment. The operation followed four distinct phases: liver mobilization, dissection of the right portal vein and right hepatic artery, extrahepatic dissection of the right hepatic vein, and parenchymal transection with harmonic shears and linear staplers for division of segment 5 and 8 branches of the middle hepatic vein. No Pringles' maneuver was used. In contrast to liver resection for other indications, the right bile duct was enlarged and filled with stones. It was divided during parenchymal transection and left open. After removal of the surgical specimen, the biliary tree was flushed with saline until stone clearance, under radioscopic surveillance, was complete. The right hepatic duct then was closed with running suture. RESULTS: The operative time was 240 min, and the estimated blood loss was 120 ml, with no blood transfusion. The hospital stay was 5 days. At this writing, the patient is well and asymptomatic 7 months after the procedure. CONCLUSION: Laparoscopic liver resection is safe and feasible for patients with hepatolithiasis and should be considered for those suffering from intrahepatic stones. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00464-007-9666-1) contains supplementary material, which is available to authorized users.

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil.

Occult hepatitis B virus (HBV) infection has been reported among patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Our aim was to evaluate the presence of occult HBV infection in patients with HCV-related liver cirrhosis (LC) with or without HCC in São Paulo, Brazil. Serum and liver tissue samples from 50 hepatitis B surface antigen-negative patients with HCV-related LC who underwent liver transplantation at the University of São Paulo School of Medicine Hospital from 1993 to 2004 were divided into groups with LC only (N = 33) and with LC plus HCC (N = 17). HBV DNA was assayed for serum and paraffin-embedded liver tissue (tumoral and non-tumoral) using real time PCR and only 1 case with HCC had HBV DNA-positive serum. All liver samples were negative. HCV genotype 3 was detected in 17/39 (43.7%) cases. In conclusion, using a sensitive real time PCR directed to detect HBV variants circulating in Brazil, occult hepatitis B infection was not found among HCV-positive cirrhotic patients and was rarely found among HCV-positive HCC patients. These results are probably related to the low prevalence of HBV infection in our population. Furthermore, we have also shown that HCV genotype 3 is frequently found in Brazilian cirrhotic patients, particularly when they also have HCC. More studies involving a large number of cases should be carried out to confirm these data and to further characterize Brazilian HCV genotype isolates to elucidate genetic features that might be related to its carcinogenic potential.

Small bowel and colon transplantation in rats using porto-portal cuff anastomosis.

Portal versus systemic venous drainage and colon grafting are major controversies in the techniques of intestinal transplantation. The rat is the best animal for research in this field. Nevertheless, this model requires complex microvascular anastomoses that are responsible for the high incidence of technical failures. A cuff technique is an easier anastomosis method than a hand-suture. We describe a simplified rat model of small bowel and colon transplantation using a porto-portal cuff anastomosis. DONOR: The entire small bowel, cecum, and ascending colon are harvested on a vascular pedicle, consisting of a long aortomesenteric conduit and portal vein. The right colonic vessels are preserved. The graft is flushed and a cuff device is placed on the end of the portal vein. RECIPIENT: The graft is implanted through an end-to-side aorto-aorta hand-sewn anastomosis. A segment between the first and second jejunal branch is isolated between clamps to insert into the portal cuff. After reperfusion, the recipient's mesentery is divided just below the cuff anastomosis. The recipient jejunum, ileum, and ascending colon are removed en bloc, and the graft is anastomosed in continuity with the remaining naive intestine concluding the operation. This simplified technique surmounts the technical obstacles in rats because it is easily and quickly performed, maintaining the physiological portal drainage, preserving graft ileocecal valve and ascending colon, and reaching acceptable success after a short period of training.

Surgical and interventional treatment of chronic pancreatitis.

The management of patients with chronic pancreatitis (CP) remains a challenging problem. Main indications for surgery are intractable pain, suspicion of malignancy, and involvement of adjacent organs. The main goal of surgical treatment is improvement of patient quality of life. The surgical treatment approach usually involves proximal pancreatic resection, but lateral pancreaticojejunal drainage may be used for large-duct disease. The newer duodenum-preserving head resections of Beger and Frey provide good pain control and preservation of pancreatic function. Thoracoscopic splanchnicectomy and the endoscopic approach await confirmatory trials to confirm their efficiency in the management of CP. Common bile duct obstruction is addressed by distal Roux-en-Y choledochojejunostomy but when combined with dudodenal obstruction must be treated by pancreatic head resection. Pancreatic ascites due to disrupted pancreatic duct should be treated by internal drainage. The approach to CP is multidisciplinary, tailoring the various therapeutic options to meet each individual patient's needs.

The first clinical liver transplantation of Brazil revisited.

The first clinical orthotopic liver transplantation in Brazil was performed on August 5, 1968. The patient was awake after surgery and died on the seventh postoperative day due to subdural hematoma, bronchopneumonia, renal failure, and graft rejection. The report of this case is important to understand the evolution of clinical liver transplantation in Brazil, where this procedure is now routinely carried out in many medical centers.

Early mortality in liver transplantation: bilirubin as predictor of outcome.

The shortage of donor organs and the long waiting lists have increased the need to better select liver transplant candidates using predictors of success. We reviewed the results of 29 liver transplantations performed from January 2002 to February 2003 analyzing the correlations with early mortality (30 days) of patient data, pretransplant laboratory data, warm ischemia time, intraoperations blood unit transfusions, and postoperative complications of prolonged mechanical ventilation, dialysis, and infection. Overall early mortality was 27.6% and 44% in fulminant hepatic failure (n = 9), there were four retransplants with one death, and two intraoperative deaths. Only pretransplant bilirubin (P =.045) and postoperative lactate levels (P =.002) were significantly different between alive versus dead patients. In this small population bilirubin was more related to death than the MELD score. Lactate levels, nonspecific predictor of death in shock syndromes were probably related to septic complications.

Biliary reconstruction without T-tube in liver transplantation.

Biliary complications have been reported in 9% to 34% of liver transplant patients. Although most centers seem to prefer a duct-to-duct anastomosis without a T-tube when feasible, the best method of biliary reconstruction remains controversial. The aim of this study was to review our experience on reconstruction of the biliary tract without drainage. Forty-one patients underwent 45 liver transplants over two periods. Forty patients underwent 15 liver transplants from October 1992 to March 1995; and 27 underwent 30 liver transplants from January 2002 to February 2003. Our standard biliary reconstruction was an end-to-end anastomosis without drain. The overall actuarial survival was 72.7% at 1 year, 64.7% at 3 years, and 56.6% at 5 years. The mean follow-up was 23 months. Eight patients (22.2%) developed biliary tract complications: five patients papillary dysfunction (13.9%); two, biliary stricture (5.5%); and one, biliary sludge without evidence of stricture (2.8%). Papillary dysfunction represented 62.5% of all complications. Biliary reconstruction without drainage may be routinely performed since the complications are only those not related to the T-tube.

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.

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.

Preoperative diagnosis of pancreatic leiomyosarcoma.

BACKGROUND: The low incidence of pancreatic leiomyosarcoma is responsible for the small number of cases correctly diagnosed preoperatively, the tumor being frequently confused with benign pancreatic lesions. RESULTS: We describe a symptom free 52-yr-old male bearing an abdominal mass incidentally found at physical examination. Imaging techniques revealed a nonhomogenous large mass at the head of the pancreas that dislodged the portal vein and the superior mesenteric vein. Increased metabolic activity in the tumor area demonstrated by 18F-fluorodeoxyglicose positron emission tomography scan allowed the diagnosis of a malignant lesion. The patient was operated on and a pylorus preserving pancreatoduodenectomy performed. The pathology diagnosis was a low grade leiomyosarcoma. Immunohistochemistry revealed positivity for vimentin and smooth muscle specific actin. The clinical course was uneventful after 2 yr follow-up. CONCLUSION: Pancreatic leiomyosarcoma may be preoperatively diagnosed by image techniques and differentiated from benign lesions by means of fluorodeoxyglicose positron emission tomography scanning (FDGPET).

Hepatic adenoma and focal nodular hyperplasia: differential diagnosis and treatment.

The diagnosis of benign hepatic tumors as hepatic adenoma (HA) and focal nodular hyperplasia (FNH) remains a challenge for clinicians and surgeons. The importance of differentiating between these lesions is based on the fact that HA must be surgically resected and FNH can be only observed. A series of 23 female patients with benign liver tumors (13 FNH, 10 HA) were evaluated, and a radiologic diagnostic algorithm was employed with the aim of establishing preoperative criteria for the differential diagnosis. All patients were submitted to surgical biopsy or hepatic resection to confirm the diagnosis. Based only on clinical and laboratory data, distinction was not possible. According to the investigative algorithm, the diagnosis was correct in 82.6% of the cases; but even with the development of imaging methods, which were used in combination, the differentiation was not possible in four patients. For FNH cases scintigraphy presented a sensitivity of 38.4% and specificity of 100%, whereas for HA the sensitivity reached 60% and specificity 85.7%. Magnetic resonance imaging, employed when scintigraphic findings were not typical, presented sensitivities of 71.4% and 80% and specificities of 100% and 100% for FNH and HA, respectively. Preoperative diagnosis of FNH was possible in 10 of 13 (76.9%) patients and was confirmed by histology in all of them. In one case, FNH was misdiagnosed as HA. The diagnosis of HA was possible in 9 of 10 (90%) adenoma cases. Surgical biopsy remains the best method for the differential diagnosis between HA and FNH and must be performed in all doubtful cases. Surgical resection is the treatment of choice for all patients with adenoma and can be performed safely. With the evolution of imaging methods it seems that the preoperative diagnosis of FNH may be considered reliable, thereby avoiding unnecessary surgical resection.