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.

Glucagon test in insulinoma: Is it useful?

Diagnosis of endogenous hyperinsulinism caused by insulinoma is based on confirmation of hypoglycemia during the symptoms associated to elevated insulin levels. Patients with insulinoma may demonstrate an excessive insulin response and subsequent hypoglycemia after 1 mg of glucagon iv injection. Glucagon test was performed in 11 patients with insulinoma before therapy and in 4 after therapy. Our study suggests that the presence of plasma glucose levels less than 55 mg/dl and below baseline at time 120 min of glucagon test strongly reinforce the diagnosis of insulinoma.

Poor prognosis indicators of type-2 diabetic COVID-19 patients.

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

Total pancreatectomy: porcine model for inducing diabetes - anatomical assessment and surgical aspects.

BACKGROUND: The swine is an essential model for carrying out preclinical research and for teaching complex surgical procedures. There is a lack of experimental models describing anatomical and surgical aspects of total pancreatectomy in the pig. MATERIALS AND METHODS: The experiments were performed on 10 white male swine weighing 27-33 kg. The animals were premedicated with midazolam (0.4 mg/kg, i.m.) and ketamine (4 mg/kg, i.m.). Anesthesia was induced with propofol (1-2 mg/kg, i.v.) and was maintained with propofol and fentanyl (0.3 mg and 0.1 µg/kg/min, respectively, i.v.). The surgical period ranged from 44 to 77 min. The pancreas anatomy, and the main arterial, venous and pancreatic duct anatomy were assessed. RESULTS: The pancreas anatomy was composed of 3 lobes, the 'splenic', 'duodenal' and 'connecting' lobe which is attached to the anterior portion of the portal vein. The splenic artery and the junction of the splenic vein and portal vein were divided. The left gastric artery was dissected and separated from its origin at the splenic artery. The head of the pancreas is disposed in a C shape. The pancreas was dissected and liberated from the right portion of the portal vein and the infrahepatic vena cava. The pancreas was separated from the duodenum preserving the pancreaticoduodenal artery, then we performed the total pancreatectomy preserving the duodenum, common bile duct and spleen. CONCLUSION: Total pancreatectomy with duodenum, bile duct and spleen preservation in the pig is feasible and an important instrument for research purposes and teaching surgical technique.

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.

Poor prognosis indicators of type-2 diabetic COVID-19 patients

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease.

Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7) or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7) for 4 weeks. The control group (N = 7) was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4) and a decrease in respiratory control rate (RCR) in the CD group (S4: 32.70 +/- 3.35; RCR: 2.55 +/- 0.15 ng atoms of O2 min-1 mg protein-1) when compared to the H and control groups (S4: 23.09 +/- 1.53, 17.04 +/- 2.03, RCR: 3.15 +/- 0.15, 3.68 +/- 0.15 ng atoms of O2 min-1 mg protein-1, respectively), P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

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.

Systematic use of isolated pancreatic anastomosis after pancreatoduodenectomy: Five years of experience with zero mortality.

OBJECTIVE: The aim of this study is to perform a comprehensive evaluation of 5 years of experience with the technique of isolated pancreatic anastomosis reconstruction after pancreatoduodenectomy from the perspective of safety and surgical efficacy using a prospective database. METHODS: The study included all consecutive patients undergoing pancreatoduodenectomy from April 2009 to April 2014 at a single referral center for hepato-pancreato-biliary diseases. The primary endpoint was the safety of the procedures, which was assessed as the occurrence of complications during hospitalization. Ninety-day mortality was also assessed. Postoperative pancreatic fistulas were classified as grade A, B, or C according to the International Study Group of Pancreatic Fistula classification. RESULTS: The study group included 214 consecutive patients with a median age of 60 years who underwent pancreatoduodenectomy. Portal vein resection was performed on 41 patients. Indications for resection were 165 pancreatic head tumors, 33 ampullary tumors, 7 chronic pancreatitis, 3 distal bile duct tumors, and 6 duodenal tumors. There was no perioperative or 90-day mortality in this series. Complications occurred in 68 patients (32%), and 42 patients presented with pancreatic fistulas (19.6%). Grade A fistulas were present in 38 patients. Three patients presented persistent pancreatic fistula and were treated with percutaneous drainage. One patient developed combined pancreatic and biliary fistulas and was reoperated on for pancreatic abscess drainage. CONCLUSIONS: The technique of isolated pancreatic anastomosis by diverting the pancreatic from biliary secretion may contribute to reducing the severity of pancreatic fistulas and therefore the severity of this complication.

Interferon alpha-2B and liver resection to treat multifocal hepatic epithelioid hemangioendothelioma: a relevant approach to avoid liver transplantation.

BACKGROUND: Hepatic epithelioid hemangioendothelioma is a rare malignant tumor of vascular origin with frequent multifocal appearance. Liver resection may cause tumor spread. Liver transplantation has been indicated for unresectable nodules. We hypothesized that adjuvant interferon treatment is effective to prevent metastasis after liver resection. We report a case of multifocal hepatic epithelioid hemangioendothelioma successfully treated with interferon pulse therapy and bilobar hepatic resection. METHODOLOGY: CT scan and magnetic resonance imaging diagnosed three nodules in the liver (segments IV, VI and VII). Histopathology and specific immunostaining of a percutaneous nodule biopsy confirmed the diagnosis of hepatic epithelioid hemangioendothelioma. The treatment protocol included daily interferon alpha 2b 9 weeks before and 1 week after resection of liver segments IV, VI and VII. RESULTS: The postoperative outcome was complicated by a self-limited biliary fistula. The patient remains tumor free at 3 years after liver resection and currently enjoys excellent health. CONCLUSION: Interferon pulse therapy and hepatic resection was a good option to treat multifocal bilobar hepatic epithelioid hemangioendothelioma; it may prevent metastasis dissemination.

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.

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.

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.

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%) 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.

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.

Radial endoscopic ultrasound and spiral computed tomography in the diagnosis and staging of periampullary tumors.

BACKGROUND AND STUDY AIMS: The early detection and accurate staging of pancreatic and ampullary cancer is of utmost importance for the achievement of surgical radical treatment. The aim of this study was to assess prospectively the role of endoscopic ultrasonography (EUS) in detection and staging of pancreatic and ampullary cancer, comparing its results to those obtained with spiral computed tomography (SCT). PATIENTS AND METHODS: Sixty-one patients with suspected pancreatic and ampullary tumors were included, 46 (75, 4%) of whom presented with obstructive jaundice. Patients underwent EUS and SCT within a 7-day period. Examiners were unaware of the previous imaging results, except conventional echography. Image interpretation was compared to surgical and histopathological findings. RESULTS: Fifty-six (91, 8%) patients were surgically explored. Clinical follow-up and/or tissue diagnosis determined the correct diagnosis in the remaining five patients. Pancreatic cancer and ampullary cancer were observed in 29 (47, 6%) and 10 (16, 4%) patients, respectively. Chronic pancreatitis and choledocholithiasis were the most common diagnosis in patients with non-neoplastic disease. EUS was more effective than SCT for the definition of the final diagnosis in patients with obstructive jaundice (87.0 vs. 67.4%, p = 0.04). Both exams were equally effective for detecting pancreatic cancer but EUS predicted more accurately the involvement of portal-mesenteric axis by the tumor (87.0 vs. 67.4%, p = 0.04). EUS was particularly useful in the diagnosis of cancer of papilla of Vater. CONCLUSION: In patients with pancreatic adenocarcinoma without unequivocal signs of distant metastatic disease, EUS is more accurate than SCT to predict venous involvement by the tumor. EUS is superior to SCT to detect ampullary adenocarcinoma. Both methods are equally ineffective to detect nodal involvement in pancreatic and ampullary cancer.