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George J Netto

Publications and source records attributed to George J Netto.

11 recordsLinked to original sources
PubMed2006

Liver and kidney transplantation for polycystic liver and kidney-renal function and outcome.

BACKGROUND: Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. METHODS: Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. RESULTS: Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36). CONCLUSION: Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Adult↗
PubMed2006

Widespread high-grade prostatic intraepithelial neoplasia on prostatic needle biopsy: a significant likelihood of subsequently diagnosed adenocarcinoma.

In comparison with earlier studies, recent reports have demonstrated a lower incidence of prostate carcinoma after an initial diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN). The latter has led to a general tendency to reconsider the absolute need for a rebiopsy in this setting. The current retrospective study assesses the subsequent likelihood of identifying prostatic adenocarcinoma (PCa) in 41 patients with an initial diagnosis of "widespread" HGPIN defined as HGPIN present in 4 or more biopsy cores. All patients underwent at least 1 follow-up (F/U) sampling procedure in a period of 1 to 41 months. PCa was found in 16/41 patients (39%), all except 1 identified on the first F/U biopsy with the remaining patients diagnosed on a transurethral resection after a negative first F/U biopsy. All but 1 prostatic carcinoma diagnoses were obtained within 2 years from initial biopsy with 10 rendered within the first year. On average, prostate cancer was identified at 10.4 months (range: 1 to 36). One-fourth of all identified prostatic carcinomas were of Gleason score 7 or more. In 4 additional patients (9.7%), F/U biopsy revealed HGPIN with adjacent atypical small glands suspicious but not diagnostic of carcinoma (PINATYP). Of 41 patients, 10 (24.3%) continued to show HGPIN with the remaining 11/41 patients (26.8%) showing benign prostatic tissue. Patients >or=70 years of age at the time of initial biopsy had a statistically significant higher rate of PCa or HGPIN/PINATYP diagnosis on repeat biopsy compared with younger patients (P=0.02), with 55% of older men being diagnosed with cancer as compared with 33% in younger men. Patients with fewer cores sampled on initial biopsy were more likely to be diagnosed with carcinoma as opposed to HGPIN/PINATYP on F/U (P=0.015). Other factors such as the number of F/U procedures, serum prostate-specific antigen level before initial HGPIN biopsy, number of cores per F/U biopsy, and F/U interval length did not affect the likelihood of finding carcinoma. In summary, our study reveals a 39% risk of finding PCa on repeat biopsies obtained after an initial diagnosis of widespread HGPIN. Our findings support the need for a repeat biopsy in this subset of patients.

Adenocarcinoma↗
PubMed2006

Interobserver agreement in hepatitis C grading and staging and in the Banff grading schema for acute cellular rejection: the "hepatitis C 3" multi-institutional trial experience.

CONTEXT: Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials. OBJECTIVE: To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the "Hepatitis C 3" trial. DESIGN: The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin-stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs. RESULTS: Statistically significant agreement was found among all participating pathologists (P < .001). On kappa analysis, the degree of agreement was rated "moderate" for HCV grade and stage and ACR global grading (kappa = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (kappa = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (kappa = 0.76 "almost perfect" for HCV and 0.62 "substantial" for ACR). CONCLUSIONS: An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.

Acute Disease↗
PubMed2006

Diagnostic molecular pathology: an increasingly indispensable tool for the practicing pathologist.

CONTEXT: Diagnostic molecular pathology is rapidly becoming an indispensable tool for anatomic pathologists. Familiarity with some of the technologic principles and current, as well as upcoming, molecular diagnostic applications is greatly advantageous for today's practice of pathology. OBJECTIVES: To provide a discussion of the most common techniques currently used in molecular pathology laboratories and review their essential applications to diagnosis and management of neoplastic diseases. DATA SOURCES: A literature review and illustrative cases from the authors' molecular diagnostic practices. CONCLUSIONS: Applications such as clonality assays, molecular cytogenetics, and chimerism analysis are providing us with accurate tools to resolve difficult diagnostic and management decisions in hemato-oncology. This should serve as a future model to expand molecular applications into the wider field of solid tumors.

Chromosome Painting↗
PubMed2005

Cadaveric orthotopic auxiliary split liver transplantation and kidney transplantation: an alternative for type 1 primary hyperoxaluria.

Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxaluria (PH1). It has been advocated in combination with kidney transplantation (KTX) in patients with renal failure from PH1 because KTX alone can result in early graft loss. A 58-year-old male patient with PH1 on hemodialysis underwent resection of the left lateral segment of the liver followed by orthotopic auxiliary left lateral segment liver transplantation and kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8 micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1 micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX is an alternative to whole LTX in PH1. By using a split deceased donor liver, it does not deprive the donor pool and protects the recipient from liver failure in case of graft loss.

Cadaver↗
PubMed2003

The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation.

BACKGROUND: Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. MATERIALS AND METHODS: The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. RESULTS: Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3 use (P=0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P=0.11). CONCLUSIONS: Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.

Drug Therapy, Combination↗
PubMed2003

Pretransplant MELD score as a predictor of outcome after liver transplantation for chronic hepatitis C.

The Model of End-Stage Liver Disease (MELD) score, an accurate predictor of mortality in patients awaiting liver transplantation (OLTX), did not predict graft or patient survival in the post-transplant setting. Our aim was to test the model in patients who underwent OLTX for chronic hepatitis C. Two hundred and eighty-seven adult patients who underwent primary OLTX for chronic hepatitis C between December 1993 and September 1999 were studied from a prospectively maintained database. The group was stratified by MELD scores of less than 15, 15-24, and greater than 24. Patient survival, graft survival, and interval liver biopsy pathology were reviewed. Both patient and graft survival at 3, 6, and 12 months were significantly lower in the higher MELD score groups, as was patient survival at 24 months (p-values, 0.01-0.05). The difference in survival between the low, medium, and high MELD score groups increases in time. The survival without bridging fibrosis in the allograft at 1 year post-transplant was significantly lower with higher MELD scores (p = 0.037). The decrease in survival seen in hepatitis C patients with MELD scores greater than 24 raises questions of transplant suitability for these patients. Therapeutic modalities to decrease post-transplant graft injury in these patients should be explored.

Adult↗
PubMed2002

Hematologic aspects of liver transplantation for Budd-Chiari syndrome with special reference to myeloproliferative disorders.

BACKGROUND: Patients who undergo orthotopic liver transplantation (OLT) for Budd-Chiari syndrome (BCS) traditionally have been anticoagulated with warfarin postoperatively. Because a significant proportion of BCS patients are found to have an underlying myeloproliferative disorder (MPD), antiplatelet therapy may be a more rational treatment strategy for this subgroup. METHODS: All patients who underwent OLT for the diagnosis of BCS at our institution through March 2000 were included in this analysis. Posttransplant therapy consisted of hydroxyurea and aspirin for those with MPDs. Standard anticoagulation or no antithrombotic treatment was given to BCS patients with other causes. Major posttransplantation complications (thrombosis and bleeding) and mortality were determined. RESULTS: Seventeen patients underwent OLT for BCS at our institution. The mean follow-up was 68.4 months. Two of seventeen patients died; one patient died of recurrent thrombosis (124 months after OLT) and the other patient died of acute hepatitis B (7 months after OLT). Twelve patients (71%) had evidence of a MPD. Two of the MPD patients were treated with warfarin before the initiation of hydroxyurea and aspirin therapy. The remaining 10 MPD patients were placed on only hydroxyurea and aspirin after OLT. Anagrelide was used in place of hydroxyurea in two patients because of cytopenias caused by the latter agent. The mean follow-up of this group of 10 patients was 59.9 months. Only one patient experienced recurrent thrombosis, which occurred more than 10 years after the original transplant. There were no major bleeding complications and posttransplant liver biopsies were well tolerated. CONCLUSIONS: Antiplatelet therapy that consists of hydroxyurea and aspirin is a safe and effective alternative to anticoagulation to prevent recurrent thrombosis in MPD patients with BCS after liver transplantation. For patients with a hypercoagulable state corrected by OLT, antithrombotic therapy probably is not required. For those patients with conditions not corrected by OLT or with idiopathic BCS, anticoagulation or other therapy to control the hypercoagulable state should be given.

Adolescent↗
PubMed2002

Incidence and recurrence of autoimmune/alloimmune hepatitis in liver transplant recipients.

We prospectively collected data on 1,429 liver transplant recipients between December 1984 and December 1998. Fifty-five patients (3.8%; 10 men, 45 women; median age, 44.5 +/- 13 [SD] years) with autoimmune hepatitis (AIH) underwent orthotopic liver transplantation (OLT). Transplant recipients with AIH were younger, more likely to be women, and had a greater likelihood of rejection in the first 3, 6, and 12 months. There was no difference in patient survival or graft survival. There were 11 biopsy-proven recurrences (1 man, 10 women) of AIH after OLT. Almost half the episodes occurred within the first year after OLT. No patient required re-OLT because of recurrent disease. AIH has an incidence of 4% and a recurrence rate of 20% in OLT. Transplant recipients are more likely to be young women and have an increased incidence of acute cellular rejection (ACR) during the first post-OLT year. Recurrence should be suspected in those with abnormal liver function test results in the absence of ACR, especially during the first year after OLT. We cannot establish with certainty whether the observed process represents recurrence of the original autoimmune disease, an alloimmune phenomenon, or allograft dysfunction mimicking AIH.

Adult↗
PubMedDate not supplied

Radiofrequency thermal ablation of hepatocellular carcinoma before liver transplantation--a clinical and histological examination.

BACKGROUND: Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is an optional treatment for patients awaiting liver transplantation (LTX). The study evaluates the efficacy of RFA in the explanted liver and its effect on patient outcome. MATERIAL AND METHOD: Forty-seven patients underwent RFA and were listed for transplant between January 1998 and May 2003. The patients were divided into two groups: transplanted and non-transplanted. Both groups were evaluated in terms of tumor characteristics, recurrence, mortality rate, and time on the waiting list. The ablation sites in the explanted livers were examined for percentage of necrosis by Hematoxylin & Eosin (H&E) stain and by TUNEL stain. RESULTS: Transplantation was carried out in 35 patients (74.5%). Ten patients (21.3%) died before transplant or were removed from the wait list, while two patients (4.2%) are still listed. Mortality and tumor-related mortality were significantly higher in the non-transplanted group. The time spent on the waiting list was longer in the non-transplanted patients (350 vs. 186 d average, p = 0.0345). Thirty-eight ablation sites were examined in the explanted livers. The percentage of tumor necrosis by TUNEL staining was 19.6% higher than that reported by H&E staining. After TUNEL staining, 28 sites (73.7%) had more than 90% necrosis, eight sites (21.0%) had 50-90%, and two sites (5.3%) had less than 50% necrosis. CONCLUSIONS: RFA and LTX can be used successfully in HCC patients, and in most cases, tumor necrosis can be achieved with ultrasound-guided RFA. H&E stain tends to under-represent the amount of tumor necrosis on the ablation sites. Survival of RFA patients after LTX is excellent.

Biopsy↗