Splanchnic non-hepatic hemodynamics and metabolism during liver transplantation

Background/Aims: The aim of this study is to compare the splanchnic non-hepatic hemodynamics and the metabolic changes during orthotopic liver transplantation between the conventional with bypass and the piggyback methods. Methodology: A prospective, consecutive series of 59 primary transplants were analyzed. Oxygen consumption, glucose, potassium, and lactate metabolism were quantitatively estimated from blood samples from the radial artery and portal vein, collected up to 120 minutes after graft reperfusion. Mean arterial pressure, portal venous pressure, portal venous blood flow, and splanchnic vascular resistance were also measured or calculated at postreperfusion collection times. Results: There was a greater increase in portal venous blood flow (p=0.05) and lower splanchnic vascular resistance (p=0.04) in the piggyback group. Mean arterial pressure and portal venous pressure were similar for both groups. Oxygen, glucose and potassium consumption were higher in the piggyback group, but none of the metabolic parameters differed significantly between groups. Conclusions: In conclusion, the study detected a higher portal venous blood flow and a lower and splanchnic vascular resistance associated with the piggyback technique. After graft reperfusion, no difference in the splanchnic non-hepatic metabolic parameters was observed between the conventional with bypass and the piggyback methods of orthotopic liver transplantation.

Organ-Sparing Microsurgical Resection of Incidental Testicular Tumors Plus Microdissection for Sperm Extraction and Cryopreservation in Azoospermic Patients: Surgical Aspects and Technical Refinements

INTRODUCTION The management of nonpalpable testicular masses is a challenging task, and coexisting infertility can further complicate the treatment decisions. We present our technique for microsurgical organ-sparing resection of incidental nonpalpable testicular nodules combined with microdissection for testicular sperm extraction and tissue cryopreservation in azoospermic patients. TECHNICAL CONSIDERATIONS Five infertile patients with azoospermia presented with nonpalpable hypoechoic testicular masses that were detected by Ultrasonography and underwent organ-sparing surgery. The testis was delivered through an inguinal incision, and the blood circulation was interrupted with a vascular clamp placed on the spermatic cord. Sludged ice was used to prevent warm ischemia, and a temperature probe was used to control the temperature at 12 degrees-15 degrees C. Real-time reflex ultrasonography was used to locate the tumor, and a stereotaxic hook-shaped needle was inserted under ultrasound guidance. The needle was placed adjacent to the tumor to guide the microsurgical resection. The tunica albuginea was incised over the tumor, which was dissected and removed, along with the adjoining parenchymal tissue. Frozen section studies were performed and, if malignancy was confirmed, biopsies of the tumor cavity margins and remaining parenchyma were obtained to ensure the absence of residual tumor. Microdissection was performed for excision of selected enlarged tubules that were processed and cryopreserved. CONCLUSIONS We present a technique for microsurgical organ-sparing resection of testicular tumor and sperm extraction that can be used in selected infertile patients with azoospermia in whom incidental masses have been diagnosed by ultrasonography. This conservative approach should be especially considered for patients with a solitary testis or bilateral tumors. UROLOGY 73: 887-892, 2009. (C) 2009 Elsevier Inc.

On the validity of the dispersion model of hepatic drug elimination when intravascular transit time densities are long-tailed

The dispersion model with mixed boundary conditions uses a single parameter, the dispersion number, to describe the hepatic elimination of xenobiotics and endogenous substances. An implicit a priori assumption of the model is that the transit time density of intravascular indicators is approximated by an inverse Gaussian distribution. This approximation is limited in that the model poorly describes the tail part of the hepatic outflow curves of vascular indicators. A sum of two inverse Gaussian functions is proposed as ail alternative, more flexible empirical model for transit time densities of vascular references. This model suggests that a more accurate description of the tail portion of vascular reference curves yields an elimination rate constant (or intrinsic clearance) which is 40% less than predicted by the dispersion model with mixed boundary conditions. The results emphasize the need to accurately describe outflow curves in using them as a basis for determining pharmacokinetic parameters using hepatic elimination models. (C) 1997 Society for Mathematical Biology.

Interconnected-tubes model of hepatic elimination

The distributed-tubes model of hepatic elimination is extended to include intermixing between sinusoids, resulting in the formulation of a new, interconnected-tubes model. The new model is analysed for the simple case of two interconnected tubes, where an exact solution is obtained. For the case of many strongly-interconnected tubes, it is shown that a zeroth-order approximation leads to the convection-dispersion model. As a consequence the dispersion number is expressed, for the first time, in terms of its main physiological determinants: heterogeneity of flow and density of interconnections between sinusoids. The analysis of multiple indicator dilution data from a perfused liver preparation using the simplest version of the model yields the estimate 10.3 for the average number of interconnections. The problem of boundary conditions for the dispersion model is considered from the viewpoint that the dispersion-convection equation is a zeroth-order approximation to the equations for the interconnected-tubes model. (C) 1997 Academic Press Limited.

Predictive factors for local recurrence and incomplete resection of early gastric cancer treated by endoscopic resection: A Western experience

BACKGROUND: Early gastric cancer (EGC) is defined as adenocarcinoma limited to the mucosa or submucosa regardless of lymph node involvement. Local EGC recurrence rates have been described ill Lip to 6% of cases. OBJECTIVES: To evaluate predictive factors for incomplete resection and local recurrence of EGC treated by endoscopic mucosal resection (EMR) that was followed up for at least one year. METHODS: From June 1994 to December 2005, 46 patients with EGC underwent EMR. Possible predictive factors for incomplete endoscopic resection and local recurrence were identified by medical chart analysis. Demographic, endoscopic and histopathological data were retrospectively evaluated. EMR was considered complete or incomplete. Patients from the complete resection group were divided into subgroups (with and without local EGC recurrence). RESULTS: Complete resection was possible in 36 cases (76.6%). Predictive factors for incomplete resection were turnout location (P=0.035), histological type (P=0.021), lesion size (P=0.022) and number of resected fragments (P=0.013). On multivariate analysis, undifferentiated histological type (OR 0.8; 95% Cl 0.036 to 0.897) and number of resected fragments (OR 7.34; 95% Cl 1.266 to 42.629) were independent predictive factors for incomplete resection. In the complete resection group, a larger lesion size was associated with a higher the number of resected fragments (P=0.018). Local recurrence occurred in nine cases (25%). Use of the cap technique was the only predictive factor for local recurrence in five of seven cases (71.4%) (P=0.006). CONCLUSIONS: A larger lesion size was associated with a higher number of resected fragments. Undifferentiated adenocarcinoma and piecemeal resection were predictive factors for incomplete resection. Technique type was a predictive factor for local EGC recurrence.

Clinical and pathologic prognostic factors for curative resection for pancreatic cancer

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

Laparoscopic right hemihepatectomy for hepatolithiasis

Background Liver resection is the definitive treatment for unilateral hepatolithiasis [1]. Recently, laparoscopic major hepatectomias have become more common and are being performed in highly specialized centers [2-4]. However, few laparoscopic liver resections for hepatolithiasis have been reported. Chen et al. [5] 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 [1] 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.

Chronic hepatitis C: Hepatic fibrosis evolution after ineffective specific treatment

Background/Aims: Specific treatment of chronic hepatitis C is effective in 50% of patients, improving the]liver`s fibrosis, necroinflammatory changes and steatosis. However, in patients still viremic after treatment the extension of these benefits remains doubtful. The evolution of the disease in this group and its relationship to demographic data, biometric indices and time lapse between biopsies was evaluated. Methodology: In 141 patients, paired biopsies were classified and compared according to fibrosis grading. Necroinflammation, steatosis, demographic data (age and gender), body mass index (BMI) and time lapse between biopsies were compared with fibrosis grading. Results: The grade of fibrosis of the patients, after approximately 3.5 years time lapse between biopsies, could be classified into 4 groups; Improved: 29(20.0%), Unaltered: 64(45.0%), Worsened: 48(34%) and Cirrhotic: 14(9.93%). For necroinflammation, the Improved/Unaltered groups were statistically similar but different from the Worsened and Cirrhotic. The mean age, BMI and time lapse between biopsies were statistically similar in all groups. Steatosis occurred in 35 (24.82%) between biopsies and its incidence was reduced in the Worsened and Cirrhotic groups. Conclusions: Fibrosis turned into cirrhosis in a significant number of patients, after a short time lapse. The reverse correlation of steatosis to fibrosis and its occurrence during the time lapse between biopsies suggests it might induce hepatic necrosis and contribute to fibrogenesis.

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.

TGF-beta and mesenchymal hepatic involvement after visceral leishmaniasis

The liver involvement in the human visceral leishmaniasis (VL) has been related to parasitism and activated Kupffer cells with further occasional fibrotic alterations, especially after long-term disease without treatment. However, fibrotic alterations have been reported after therapy, whose clinical finding is the persistence of hepatomegaly. Fibrotic involvement of the liver after therapy was never well understood, and the aim of this study was to evaluate this finding through ultrastructural and morphometric analysis. A case-control study was performed with 20 patients (15 cases and five controls). Cases included patients with persistent hepatomegaly (residual) after treatment of VL submitted to liver biopsy to exclude other causes of liver enlargement, including serum tests of viral hepatitis. The material was evaluated by electron microcopy allowing ultrastructural with morphometric analysis of medium portion of hepatic lobule. Narrow sinusoidal lumen and prominent Kupffer cells were found with insignificant alterations of hepatocytes, pit, and endothelial cells. On ultrastructural analysis, the enlargement of the space of Disse was due to fibrous collagen, increase of number of Ito cells, and nonfibrous extracellular matrix that were associated with Kupffer cells enlargement. Immunohistochemistry showed an intense expression of TGF-beta in patients with VL. These findings suggest a production of TGF-beta by Kupffer cells that resulted in the characteristic fibrotic involvement of the liver. Residual hepatomegaly in visceral leishmaniasis could result from sustained Kupffer cell activation with perihepatocytic fibrosis.

Dose-dependent hepatic response to subchronic administration of nandrolone decanoate

Background: Androgenic anabolic steroids (AAS) are synthetic hormone derivatives of testosterone and are mainly used to enhance athletic performance and muscle mass, but medical applications also have been described. Short- and long-term side effects have been demonstrated in many organs, but the liver adverse effects are the most common and serious ones associated with AAS use. However, these effects have been supported by few clinical and experimental studies. Objective: To evaluate the hepatic function and structure after 5 wk of nandrolone decanoate administration at three different doses. Methods: Twenty-seven adult male Wistar rats were randomly assigned to the following groups: control, clinical, intermediate, and suprapharmacological doses of nandrolone decanoate during 5 wk. Results: The biochemical studies showed that nandrolone decanoate administration leads to a dose-dependent increase in serum levels of the aspartate aminotransferase (AST) (P < 0.05), alanine aminotransferase (ALT) (P < 0.01), and alkaline phosphatase (ALP) (P < 0.001), as well as a significant decrease in total proteins (P < 0.01), bilirubin (P < 0.05), total cholesterol and fractions (P < 0.05), and triglycerides (P < 0.05). Although a significant statistical difference was found for AST, ALT, and ALP when compared with the control group, their values remained within the normal range. The number of Kupffer cells was increased in the liver parenchyma (P < 0.05), and the content of collagen was increased in the central lobular vein wall, in the hepatic parenchyma, and in the portal space (P < 0.05). Conclusions: These results suggest that subchronic treatment with nandrolone decanoate, mainly administered at higher-than-clinical doses, are potentially deleterious to the liver, leading to incipient fibrosis.

Peritumoural, but not intratumoural, lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers

To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and LVI correlate to the classical clinical-pathological parameters, we analysed 120 cases of colorectal carcinomas selected from the files of Division of Pathology, Hospital das Clinicas, Sao Paulo University, Brazil. Assessment of LVD and LVI was performed by immunohistochemical detection of lymphatic vessels, using the monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when comparing with normal and peritumoural areas (p < 0.001). However, peritumoural LVD, but not intratumoural, correlated with both colonic-wall-invasion depth (p=0.037) and liver metastasis (p=0.012). Remarkably, LVI was found associated with local invasion (p=0.016), nodal metastasis (p=0.022) and hepatic metastasis (p < 0.001). Peritumoural LVD and LVI are directly related to histopathological variables indicative of poor outcome such as lymph-node status and liver metastasis.

Identification of hepatic stem/progenitor cells in canine hepatocellular and cholangiocellular carcinoma

Hepatic progenitor cells (HPCs) are bipotential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic or cholangiocytic lineages. HPCs are present in both hepatocellular (HCC) and cholangiocellular carcinoma (CC) in humans; and a small percentage of HCC can originate from cancer stem cells. However, its distribution in canine liver tumour has not been studied. Herein, we searched for stem/progenitor cells in 13 HCC and 7 CC archived samples by immunohistochemical analysis. We found that both liver tumours presented a higher amount of K19-positive HPCs. Besides, 61.6% of HCC cases presented immature CD44-positive hepatocytes. Nevertheless, only two cases presented CD133-positive cells. As observed in humans, hepatic canine tumours presented activated HPCs, with important differentiation onto hepatocytes-like cells and minimal role of cancer stem cells on HCC. These findings reiterate the applicability of canine model in the search for new therapies before application in humans.

Hepatic Artery Graft in Pediatric Liver Transplantation: Single-Center Experience With 58 Cases

Introduction. The use of arterial grafts (AG) in pediatric orthotopic liver transplantation (OLT) is an alternative in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, and retransplantations (re-OLT) due to hepatic artery thrombosis (HAT). AG have been crucial to the success of the procedure among younger children. Herein we have reported our experience with AG. Methods. We retrospectively reviewed data from June 1989 to June 2010 among OLT in which we used AG, analyzing indications, short-term complications, and long-term outcomes. Results. Among 437 pediatric OLT, 58 children required an AG. A common iliac artery interposition graft was used in 57 cases and a donor carotid artery in 1 case. In 38 children the graft was used primarily, including 94% (36/38) in which it was due to poor hepatic arterial inflow. Ductopenia syndromes (n = 14), biliary atresia (BA; n = 11), and fulminant hepatitis (n = 8) were the main preoperative diagnoses among these children. Their mean weight was 18.4 kg and mean age was 68 months. At the mean follow-up of 27 months, multiple-organ failure and primary graft nonfunction (PNF) were the short-term causes of death in 9 children (26.5%). Among the remaining 29 patients, 2 (6,8%) developed early graft thrombosis requiring re-OLT; 5 (17%) developed biliary complications, and 1 (3.4%) had asymptomatic arterial stenosis. In 20 children, a graft was used during retransplantation. The main indication was HAT (75%). BA (n = 15), ductopenia syndromes (n = 2), and primary sclerosing cholangitis (n = 2) were the main diagnoses. Their mean weight was 16.7 kg and age was 65 months. At a mean follow-up of 53 months, 7 children died due to multiple-organ failure or PNF. Among the remaining 13 patients, 3 developed biliary complications and 1 had arterial stenosis. No thrombosis was observed. Conclusion. The data suggested that use of an AG is useful alternative in pediatric OLT. The technique is safe with a low risk of thrombosis.