Morphology and Histochemistry of the Liver of Carnivorous Fish Hemisorubim platyrhynchos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Robotic Resection of Intraductal Neoplasm of the Pancreas

Background: Minimally invasive techniques have been revolutionary and provide clinical evidence of decreased morbidity and comparable efficacy to traditional open surgery. Computer-assisted surgical devices have recently been approved for general surgical use. Aim: The aim of this study was to report the first known case of pancreatic resection with the use of a computer-assisted, or robotic, surgical device in Latin America. Patient and Methods: A 37-year-old female with a previous history of radical mastectomy for bilateral breast cancer due to a BRCA2 mutation presented with an acute pancreatitis episode. Radiologic investigation disclosed an intraductal pancreatic neoplasm located in the neck of the pancreas with atrophy of the body and tail. The main pancreatic duct was enlarged. The surgical decision was to perform a laparoscopic subtotal pancreatectomy, using the da Vinci (R) robotic system (Intuitive Surgical, Sunnyvale, CA). Five trocars were used. Pancreatic transection was achieved with vascular endoscopic stapler. The surgical specimen was removed without an additional incision. Results: Operative time was 240 minutes. Blood loss was minimal, and the patient did not receive a transfusion. The recovery was uneventful, and the patient was discharged on postoperative day 4. Conclusions: The subtotal laparoscopic pancreatic resection can safely be performed. The da Vinci robotic system allowed for technical refinements of laparoscopic pancreatic resection. Robotic assistance improved the dissection and control of major blood vessels due to three-dimensional visualization of the operative field and instruments with wrist-type end-effectors.

Antibody-mediated rejection (AMR) after pancreas and pancreas-kidney transplantation

P>Antibody-mediated rejection (AMR) requires specific diagnostic tools and treatment and is associated with lower graft survival. We prospectively screened C4d in pancreas (n = 35, in 27 patients) and kidney (n = 33, in 21 patients) for cause biopsies. Serum amylase and lipase, amylasuria, fasting blood glucose (FBG) and 2-h capillary glucose (CG) were also analysed. We found that 27.3% of kidney biopsies and 43% of pancreatic biopsies showed C4d staining (66.7% and 53.3% diffuse in peritubular and interacinar capillaries respectively). Isolated exocrine dysfunction was the main indication for pancreas biopsy (54.3%) and was followed by both exocrine and endocrine dysfunctions (37.1%) and isolated endocrine dysfunction (8.6%). Laboratorial parameters were comparable between T-cell mediated rejection and AMR: amylase 151.5 vs. 149 U/l (P = 0.075), lipase 1120 vs. 1288.5 U/l (P = 0.83), amylasuria variation 46.5 vs. 61% (P = 0.97), FBG 69 vs. 97 mg/dl (P = 0.20) and 2-h CG maximum 149.5 vs. 197.5 mg/dl (P = 0.49) respectively. Amylasuria values after treatment correlated with pancreas allograft loss (P = 0.015). These data suggest that C4d staining should be routinely investigated when pancreas allograft dysfunction is present because of its high detection rate in cases of rejection.

Extrahepatic portal vein thrombosis after umbilical catheterization: is it a good choice for Rex shunt?

Background: Extrahepatic portal vein thrombosis (EHPVT) is an important cause of portal hypertension in children. Rex shunt has been used successfully to treat these patients. Methods: We report our experience in 19 infants and children (5 months to 14 years) with HPVT eligible for a mesenteric-portal surgical shunt with left internal jugular vein autograft. Eight children had idiopathic EHPVT, nine had post-umbilical catheterization EHPVT, one had portal vein agenesis, and one had posttransplant EHPVT. Results: It was possible to perform the Rex shunt in all patients except for 8 of 9 cases in the post-umbilical catheterization EHPVT group. A Warren procedure was performed in 4 of those patients and a proximal splenorenal shunt in 1. Current follow-up ranges from 3 to 26 months. Shunt thrombosis occurred in one patient with portal vein agenesis and associated cardiac anomaly. Portal hypertension has significantly improved after surgery. None of our patients have experienced new bleeding episodes until now. Conclusions: The Rex shunt should be considered in the treatment of children with idiopathic EHPVT experiencing repeated gastrointestinal bleeding episodes refractory to endoscopic treatment. Nevertheless, the role of this operation for children with post-umbilical catheterization EHPVT is yet to be clearly evaluated. (C) 2011 Elsevier Inc. All rights reserved.

Conversion to Sirolimus in Kidney-Pancreas and Pancreas Transplantation

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21.%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .01.8). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.

Biliary and pancreatic dysgenesis in mice harboring a mutation in Pkhd1

Autosomal recessive polycystic kidney disease is a hereditary fibrocystic disease that involves the kidneys and the biliary tract. Mutations in the PKHD1 gene are responsible for typical forms of autosomal recessive polycystic kidney disease. We have generated a mouse model with targeted mutation of Pkbd1 by disrupting exon 4, resulting in a mutant transcript with deletion of 66 codons and expression at similar to 30% of wild-type levels. Pkhd1(del4/d3l4) mice develop intrahepatic bile duct proliferation with progressive cyst formation and associated periportal fibrosis. In addition, these mice exhibit extrahepatic manifestations, including pancreatic cysts, splenomegaly, and common bile duct dilation. The kidneys are unaffected both histologically and functionally. Fibrocystin is expressed in the apical membranes and cilia of bile ducts and distal nephron segments but is absent from the proximal tubule. This pattern is unchanged in orthologous models of autosomal dominant polycystic kidney disease due to mutation in Pkd1 or Pkd2. Mutant fibrocystin in Pkhd1(del4/d3l4) mice also retains this expression pattern. The hypomorphic Pkhd1(del4/d3l4) mouse model provides evidence that reduced functional levels of fibrocystin are sufficient for cystogenesis and fibrosis in the liver and pancreas, but not the kidney, and supports the hypothesis of species-dependent differences in susceptibility of tissues to Pkbdl mutations.

Metabolic activation of aromatic amines by human pancreas

Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas, Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens, Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethylamine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/ 4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [H-3]N-hydroxy-ABP) of pancreatic cytosols was high, about two-thirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using P-32-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.

Laparoscopic Duodenal-Jejunal Bypass for the Treatment of Duodenal Obstruction Caused by Annular Pancreas: Description of a Surgical Technique

Annular pancreas is a rare congenital anomaly, which is only surgically treated in symptomatic cases. Surgical treatment consists of bypassing the duodenal transit by gastrojejunal or duodenal-jejunal anastomosis. In the absolute majority of published cases, laparotomy is the most widely used access technique. The aim of this article is to report a case of an annular pancreas and describe the technical steps involved in carrying out a laparoscopic duodenal-jejunal anastomosis, for correction of the duodenal obstruction. The patient`s recovery was uneventful; she was discharged on the fourth postoperative day and remained asymptomatic for the 2-year, outpatient follow-up period. Laparoscopic duodenal-jejunal bypass is shown to be feasible and safe, and produce less surgical trauma, when carried out by an experienced surgeon who is duly trained and familiar with the laparoscopic technique.

Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component related to a more malignant behavior?

Background/Aims: Acinar cell carcinomas are uncommon malignant tumors of the pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some authors have estimated acinar cell tumors to be as aggressive as ductal adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to have a favorable clinical outcome. This discrepancy in prognosis may be related to the cellular components of the tumor. Methodology: With the aim to evaluate the possible relationship between the presence of neuroendocrine differentiation and behavior of these tumors, the authors reviewed all patients presenting acinar cell carcinoma of the pancreas in the last 5 years with emphasis in the immunohistochemical evaluation. Results: Four patients presented neuroendocrine differentiation on immunohistochemical evaluation and had a more benign outcome. Two patients without neuroendocrine component had a disseminated disease at presentation. This data suggests that this tumor is less aggressive than ductal adenocarcinoma and even with nodal involvement, long term survival after complete resection can be achieved. Conclusions: It is possible that the absence of neuroendocrine component may be related to a less favorable outcome and adjuvant therapy may be necessary. Due to the rarity of this pancreatic tumor, this relationship remains to be confirmed with a multicentric study including a larger number of patients.

Solid pseudopapillary neoplasm of the pancreas: distinct patterns of onset, diagnosis, and prognosis for male versus female patients

Background. Solid pseudopapillary neoplasm of the pancreas is a distinctive pancreatic neoplasm with low metastatic potential. This study examines clinical differences and prognosis between male and female Patients. Methods. The medical records of 34 consecutive patients with pancreatic solid pseudopapillaly neoplasms between 1990 and 2006 were reviewed. Whenever feasible, organ-preserving operation was performed. Statistical analysis was performed using chi-square and Student t test. Results. There were 27 women (79%) and seven men (21%) with median age of 23 years. Mean diameter of the tumor was 7 cm. Tumor size tended to be smaller in patients treated in more recent years. Conservative surgery was possible in I I patients including spleen-preserving distal pancreatectomy in 3, central pancreatectomy in 5, and enucleation in 3 patients. Median hospital stay was 11 days, morbidity rate was 62%, including 17 patients with grade A pancreatic fistula, and there was no operative mortality. Mean follow-up time was 84 months. Tumor recurred in 2 patients (6%). Overall late morbidity rate was 12%. At the time of diagnosis, age was ((x) over bar +/- SD) higher among male patients (25 +/- 2 years vs 37 +/- 7 years, P < .05) with no difference in tumor size. The neoplasms were more aggressive in male Patients; therefore, conservative surgery was less likely. There was no correlation between tumor aggressiveness and age of the patient or size of tumor. Conclusion. This is the first single center study to demonstrate that solid pseudopapillary neoplasms in male patients have distinct Patterns Of onset and aggressiveness when compared with female patients. Although valid prognostic criteria are still lacking, it appears that male patients may be best treated by more radical operation and should be observed more closely during follow-up.

Long-term follow-up of children with extrahepatic portal vein obstruction: impact of an endoscopic sclerotherapy program on bleeding episodes, hepatic function, hypersplenism, and mortality

Background: Endoscopic sclerotherapy (ES) has been the standard treatment for children with idiopathic extrahepatic portal vein obstruction (EHPVO). Portosystemic shunts are indicated when variceal bleeding cannot be controlled by ES. Recently, mesenteric left portal vein bypass was indicated as a surgical intervention and preventative measure for hepatic dysfunction in children with long-term EHPVO. Nevertheless, there is a lack Of published data confirming the extent of hepatic dysfunction, hypersplenism, and physical development in children with long-term follow-up. Method: We retrospectively verified the long-term outcomes in 82 children with EHPVO treated with ES protocol, focusing on mortality, control of bleeding, hypersplenism, and consequent hepatic dysfunction. Results: Of the children, 56% were free from bleeding after the initiation of ES. The most frequent cause of rebleeding was gastric varices (30%). Four patients had recurrent bleeding from esophageal varices (4.6%). Four patients underwent surgery as a consequence of uncontrolled gastric varices. There were no deaths. Most patients showed good physical development. We observed a mild but statistically significant drop in factor V motion, as well as leukocyte and platelet count. Conclusion: Endoscopic sclerotherapy is an efficient treatment for children with EHPVO. The incidence of rebleeding is low, and there was no mortality. Children develop mild liver dysfunction and hypersplenism with long-term follow-up. Only a few patients manifest symptoms of hypersplenism, portal biliopathy, or liver dysfunction before adolescence. (C) 2009 Elsevier Inc. All rights reserved.

Laparoscopic resection of uncinate process of the pancreas

Solid pseudopapillary neoplasm of the pancreas is an uncommon but distinctive pancreatic neoplasm with low metastatic potential [1]. Therefore, whenever feasible, an organ-preserving operation should be performed. As previously reported, women with solid pseudopapillary neoplasm of the pancreas may be best treated by more conservative procedures [2]. Recently, laparoscopic pancreatic resections became more common and are being performed in highly specialized centers. There are only six cases of laparoscopic resection for solid pseudopapillary neoplasm of pancreas published in the English literature and, to our knowledge, laparoscopic resection of uncinate process of the pancreas has never been reported [3-6]. This video demonstrates the technical aspects of a totally laparoscopic resection of the uncinate process of the pancreas in a patient with solid pseudopapillary neoplasm. A 26-year-old woman with a 4-cm solid pseudopapillary pancreatic neoplasm was referred for surgical treatment. According to preoperative echoendoscopy, there was a safe margin between neoplasm and main pancreatic duct. The patient was placed in supine position with the surgeon standing between her legs. Four trocars, one 10-mm and three 5-mm, were used. At inspection, the inferior vena cava, transverse colon, duodenum, and pancreas are clearly identified. A Kocher maneuver was performed with complete exposure of pancreatic head and uncinate process. The uncinate process was dissected from the superior mesenteric vein and venous branches were divided between metallic clips or by use of laparoscopic coagulation shears (LCS; Ethicon Endo Surgery Industries, Cincinnati, OH, USA). Blood supply of the duodenum was preserved by ligature of small pancreatic branches from inferior pancreatoduodenal artery. Transection of pancreatic parenchyma was performed using laparoscopic coagulation shears, which is an effective tool for cutting the pancreas [7, 8]. Surgical specimen was removed through a suprapubic incision inside a retrieval bag. A hemostatic absorbable tissue (Surgicel; Ethicon Inc., Cincinnati, OH) was placed in the cutting pancreatic surface, and one round 19F Blake abdominal drain (Ethicon) was left in place. Operative time was 180 minutes and blood loss estimated in 40 ml with no blood transfusion. Hospital stay was 4 days. The patient did not have postoperative pancreatitis or pancreatic leakage, and the abdominal drain was removed on the tenth postoperative day. Final pathology confirmed the diagnosis of solid pseudopapillary neoplasm of pancreas with free surgical margins. The patient was well and asymptomatic 2 months after the procedure. Laparoscopic resection of uncinate process of the pancreas is safe and feasible and should be considered for patients suffering from pancreatic neoplasms.

Hepatoportal Sclerosis and Extrahepatic Portal Venous Obstruction Associated with Anti-phospholipid Antibody Syndrome in Child

We report a 2-year-old child with extrahepatic portal venous obstruction, hepatoportal sclerosis and pulmonary thromboembolism whose sole hypercoagulability factor was the presence of anti-phospholipid antibodies.

Effect of Sodium Cyclamate on the Rat Fetal Exocrine Pancreas: a Karyometric and Stereological Study

The cyclamate, a sweetner substance derived from N-cyclo-hexyl-sulfamic acid, is largely utilized as a non-caloric artificial edulcorant in foods and beverages as well as in the pharmaceutical industry. The objective of this study was to evaluate karyometric and stereological alterations in the rat fetal pancreas resulting from the intraperitoneal administration of sodium cyclamate. The exocrine pancreas of ten fetuses of rats were evaluated, five treated and five controls chosen at random, in which five rats that received from the 10th to 14th days of pregnancy an intraperitoneal daily injection of sodium cyclamate at 60 mg/Kg of body weight during 5 days. At the 20th day of gestation, the animals were removed and weighed, as were their placentas; the length of the umbilical cords also were measured. After the laboratory processing, semi-seriated 6mm cuts stained with haematoxyline and cosine were performed. In seven karyometric parameters (major, minor, and medium diameters, volume, area, perimeter, and volume-area ratio), the increase was statistically significant in the treated group when compared with control group. Stereological parameters showed in the treated group a significant increase in the cellular volume and a significant reduction in the numerical cellular density. These results showed that the sodium cyclamate in pregnant rats led to retardation of fetal development and hypertrophy in the exocrine pancreas of the rat fetuses.

Studies of the anatomy of the extrahepatic biliary tract in Mammalia.

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