Bladder neck closure in children: a decade of followup.

PURPOSE: Bladder neck closure necessitates lifelong clean intermittent catheterization. Concerns have been raised regarding well-being and compliance in patients on long-term clean intermittent catheterization. Noncompliance may result in subsequent hydronephrosis, incontinence, infection, cystolithiasis and perforation. We analyzed our long-term results with bladder neck closure followed at least 10 years for patient compliance with clean intermittent catheterization, upper tract preservation, continence, complications and subsequent procedures. MATERIALS AND METHODS: All patients followed at least 10 years after bladder neck closure were included in this study. RESULTS: Seven boys and 5 girls with a mean age of 7.0 years and urinary incontinence underwent bladder neck closure and continent urinary diversion between 1993 and 1998. The primary diagnosis was exstrophy in 5 patients, spinal dysraphism in 3, trauma in 2, sacral agenesis in 1 and a duplicated hindgut in 1. Mean followup was 12.4 years (range 10 to 14). All patients performed clean intermittent catheterization 4 to 6 times daily. Hydronephrosis improved or remained stable in the 11 patients who underwent bladder augmentation. Mild new hydronephrosis developed in 1 patient and resolved after increasing clean intermittent catheterization frequency. Bladder neck closure successfully cured incontinence in all of the last 6 patients who underwent modified bladder neck closure with a posterior bladder neck flap, while 2 of the earlier 6 bladder neck closures required revision for a subsequent 100% success rate. Additional operations were required in 6 patients. To our knowledge this is the longest followup after bladder neck closure reported in the literature. CONCLUSIONS: Patient compliance with long-term clean intermittent catheterization is good after bladder neck closure. Bladder neck closure provides excellent long-term safety for the upper urinary tract and continence. It is associated with relatively low morbidity, which is correctible.

Prolonged international normalized ratio correlates with a large intravascular fluid balance after major abdominal surgery.

We performed a prospective randomized study of 32 patients who had undergone pancreaticoduodenectomy and did not receive blood during and after surgery. The patients were prospectively assigned to two groups related to fluid balance in the immediate postoperative period. Group 1 (14 patients) were maintained at a positive intravascular fluid balance of 0-1000 mL; Group 2 (18 patients) were maintained at a positive balance of 1000-2000 mL. Complete blood counts and coagulation tests (International Normalized Ratio) and activated partial thromboplastin time (aPTT) were performed at three time points: the day before surgery, on arrival at the postanesthesia care unit, and on leaving the postanesthesia care unit (16 h later). There were significant differences in International Normalized Ratio values between the groups with deterioration during the time they were in the postanesthesia care unit but not in aPTT values. Positive correlation was found between the amount of positive fluid balance and International Normalized Ratio prolongation, but not with aPTT, suggesting that restricted intravascular fluid balance is beneficial for preservation of coagulation after major abdominal surgery.

Preclinical evaluation of two neutralizing human monoclonal antibodies against hepatitis C virus (HCV): a potential treatment to prevent HCV reinfection in liver transplant patients.

Passive immunotherapy is potentially effective in preventing reinfection of liver grafts in hepatitis C virus (HCV)-associated liver transplant patients. A combination of monoclonal antibodies directed against different epitopes may be advantageous against a highly mutating virus such as HCV. Two human monoclonal antibodies (HumAbs) against the E2 envelope protein of HCV were developed and tested for the ability to neutralize the virus and prevent human liver infection. These antibodies, designated HCV-AB 68 and HCV-AB 65, recognize different conformational epitopes on E2. They were characterized in vitro biochemically and functionally. Both HumAbs are immunoglobulin G1 and have affinity constants to recombinant E2 constructs in the range of 10(-10) M. They are able to immunoprecipitate HCV particles from infected patients' sera from diverse genotypes and to stain HCV-infected human liver tissue. Both antibodies can fix complement and form immune complexes, but they do not activate complement-dependent or antibody-dependent cytotoxicity. Upon complement fixation, the monoclonal antibodies induce phagocytosis of the immune complexes by neutrophils, suggesting that the mechanism of viral clearance includes endocytosis. In vivo, in the HCV-Trimera model, both HumAbs were capable of inhibiting HCV infection of human liver fragments and of reducing the mean viral load in HCV-positive animals. The demonstrated neutralizing activities of HCV-AB 68 and HCV-AB 65 suggest that they have the potential to prevent reinfection in liver transplant patients and to serve as prophylactic treatment in postexposure events.

Neoadjuvant imatinib for unresectable gastrointestinal stromal tumor.

We have evaluated the feasibility of the use of neoadjuvant imatinib mesylate in the management of unresectable localized gastrointestinal stromal tumors. In a pilot experience, two patients with unresectable gastrointestinal tumors were treated with neoadjuvant imatinib. Their treatment course and surgical outcomes are described. In both cases, the patient attained sufficient tumor regression to enable complete resection of tumor. We conclude that in the management of unresectable gastrointestinal stromal tumors, neoadjuvant administration of imatinib may facilitate sufficient tumor regression to facilitate subsequent tumor resection with curative intent.

Clinical outcomes of surgical resections for primary liver sarcoma in adults: results from a single centre.

BACKGROUND: Primary hepatic sarcoma is a rare tumour with a poor prognosis. METHODS: From 1997 to 2002 eight patients had liver resection for primary sarcoma of the liver at our institution. The clinical characteristics, imaging findings, surgical procedures, adjuvant therapy and outcome were retrospectively reviewed. There were two patients each with angiosarcoma (AS), leiomyosarcoma (LMS), and undifferentiated embryonal sarcoma (UES), one patient with epithelioid hemangioendothelioma (EHE) and one patient with malignant peripheral nerve sheath sarcoma (PNSS). RESULTS: The most common presenting symptoms were right upper quadrant pain and fever. Typical imaging findings were a heterogenous mass with poorly defined margins, pseudocapsule and aberrant vasculature. Preoperative diagnosis of a primary liver sarcoma was made in 7/8 cases, either by fine needle aspiration (n = 5) or angiography (n = 2). Five right hepatectomies and three trisegmentectomies were performed. An R (0) resection was possible in three cases. Two patients developed complications and there was one death. Adjuvant chemoradiotherapy was administered to 5/7 patients. Systemic chemotherapy led to tumour regression in both patients with UES which enabled a second hepatic resection. CONCLUSIONS: The majority of patients with primary liver sarcoma present with right upper quadrant pain, fever and a liver mass. Differentiating the rare primary liver sarcoma from the much more common hepatocellular carcinoma (HCC) may aid in planning therapy. Patients with resectable tumours should be referred for surgery. Liver resection combined with adjuvant chemotherapy are the mainstays of treatment for UES in the adult.

Epidural anesthesia and analgesia in liver resection.

IMPLICATIONS: In patients undergoing major liver resection, the decision to introduce an epidural catheter and the timing of its removal should be made with care because of the prolonged changes in platelet count and in prothrombin time that develop in some patients.

Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections.

BACKGROUND: Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH). METHODS: The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population. RESULTS: During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups. CONCLUSIONS: Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood.

The hepatitis C virus (HCV)-Trimera mouse: a model for evaluation of agents against HCV.

The lack of small-animal models that are suitable for evaluation of agents used to treat infection with hepatitis C virus (HCV) severely hinders the assessment of potential new therapies for the disease. This study created such a model, termed the "HCV-Trimera" model. The HCV-Trimera model was developed by using lethally irradiated mice, reconstituted with SCID mouse bone marrow cells, in which human liver fragments infected ex vivo with HCV had been transplanted. Viremia (positive-strand HCV RNA levels) in HCV-Trimera mice peaked at approximately day 18 after liver transplantation, and an infection rate of 85% was reached. Viral replication in liver grafts was evidenced by the presence of specific negative-strand HCV RNA. The usefulness of this model for evaluation of anti-HCV agents was demonstrated by the ability of a small molecule (an HCV internal ribosomal entry site inhibitor) and an anti-HCV human monoclonal antibody (HCV AB(XTL)68) to reduce virus loads in HCV-Trimera mice in a dose-dependent manner.

Analysis of differentially expressed genes in hepatocellular carcinoma using cDNA arrays.

Hepatocellular carcinoma (HCC) is characterized by multiple somatic mutations, including DNA rearrangements, that affect many cell-growth regulatory pathways. Many genes differentially expressed in HCC have been reported previously, but the patterns of expression varied significantly between patients who bore different risk factors for HCC. To identify genes whose differential expression could serve as a "signature" for diagnosis and prognosis of HCC, we performed analyses of differentially expressed genes in three cases of HCC with different risk factors using the Atlas Human Cancer cDNA Expression Arrays. Among all 597 genes present on the array, only three were found to be coordinately differentially expressed in all three HCC cases, in agreement with published data. These three genes, Cu/Zn superoxide dismutase, osteonectin/secreted protein acidic and rich in cysteine, and matrix metalloproteinase 14, could serve as candidates for the HCC "signature." Ten genes were found to be coordinately differentially expressed in only two of three tested HCC cases. On the other hand, many genes that had been reported previously as differentially expressed in HCC failed to show the described pattern of expression in this group. The results of this study confirm the great variability in gene-expression patterns in HCC and establish the utility of the array technology for identifying both the HCC signature genes and individual gene-expression patterns for purposes of patient-oriented therapy.