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I Dvorchik

Publications and source records attributed to I Dvorchik.

At least 19 recordsLinked to original sources

Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy.

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty-seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow-up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1-year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin-dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach.

Adult↗

Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C.

Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.

Adult↗

Real-time monitoring of acute liver-allograft rejection using the Banff schema.

BACKGROUND: The Banff schema is the internationally accepted standard for grading acute liver-allograft rejection, but it has not been prospectively tested. METHODS: Complete Banff grading was prospectively applied to 2,038 liver-allograft biopsies from 901 adult tacrolimus-treated primary hepatic allograft recipients between August 1995 and September 2001. Histopathologic data was melded with demographic, clinical, and laboratory data into a database on an ongoing basis using locally developed software. RESULTS: Acute rejection developed in 575 of 901 (64%) patients and the worst grade was mild in 422 of 575 (73%). At least one episode of moderate or severe acute rejection developed in 153 of 901 (17%) patients and most episodes, irrespective of severity, occurred within the first year after transplantation. Patients with moderate or severe acute rejection showed higher alanine aminotransferase (P =0.007) and aspartate aminotransferase ( P=0.07) levels and were more likely to develop perivenular fibrosis on follow-up biopsies (P =0.001) and graft failure from acute or chronic rejection ( P=0.004) than those with mild rejection. Regardless of severity, 80% of patients with acute rejection did not develop significant fibrosis in follow-up biopsies, and graft failure from acute or chronic rejection occurred in only 11 of 901 (1%) allografts. CONCLUSIONS: Most acute-rejection episodes are mild and do not lead to clinically significant architectural sequelae. When tested prospectively under real-life and -time conditions, the Banff schema can be used to identify those few patients who are potentially at risk for more significant problems. Creation, capture, and integration of non-free text, or "digital," pathology data can be used to prospectively conduct outcomes-based research in transplantation.

Acute Disease↗

An analysis of early renal transplant protocol biopsies--the high incidence of subclinical tubulitis.

To investigate the possibility that we have been underestimating the true incidence of acute rejection, we began to perform protocol biopsies after kidney transplantation. This analysis looks at the one-week biopsies. Between March 1 and October 1, 1999, 100 adult patients undergoing cadaveric kidney or kidney/pancreas transplantation, or living donor kidney transplantation, underwent 277 biopsies. We focused on the subset of biopsies in patients without delayed graft function (DGF) and with stable or improving renal function, who underwent a biopsy 8.2+/-2.6 d (range 3-18 d) after transplantation (n = 28). Six (21%) patients with no DGF and with stable or improving renal function had borderline histopathology, and 7 (25%) had acute tubulitis on the one-week biopsy. Of the 277 kidney biopsies, there was one (0.4%) serious hemorrhagic complication, in a patient receiving low molecular weight heparin; she ultimately recovered and has normal renal function. Her biopsy showed Banff 1B tubulitis. In patients with stable or improving renal allograft function early after transplantation, subclinical tubulitis may be present in a substantial number of patients. This suggests that the true incidence of rejection may be higher than is clinically appreciated.

Adult↗

De novo malignancies after liver transplantation: a major cause of late death.

1. Recurrent and de novo malignancies are the second leading causes of late death in liver transplant recipients, following age-related cardiovascular complications. 2. The increased incidence of de novo malignancies in liver transplant recipients compared with the general population reflects their demographic makeup, known preexistent risk factors for cancer, greater rate of chronic viral infection, and actions of exogenous immunosuppression. 3. The greatest incidence of de novo malignancies is seen in cancers associated with chronic viral infections, such as Epstein-Barr virus-associated posttransplant lymphoproliferative disease, and skin cancers, including squamous cell carcinoma and Kaposi's sarcoma. 4. Although a greater incidence of such malignancies as oropharyngeal malignancy and colorectal cancer was noted, there did not appear to be an increased risk for liver transplant recipients matched for age, sex, and length of follow-up using modified life-table technique and Surveillance Epidemiology End Result data with a similar at-risk group. However, they may present with more advanced stages of disease. 5. An increased incidence of de novo cancers in chronically immunocompromised liver transplant recipients demands careful long-term screening protocols to help facilitate diagnosis at an earlier stage of disease.

Humans↗

Clinical intestinal transplantation: a decade of experience at a single center.

OBJECTIVE: To assess the long-term efficacy of intestinal transplantation under tacrolimus-based immunosuppression and the therapeutic benefit of newly developed adjunct immunosuppressants and management strategies. SUMMARY BACKGROUND DATA: With the advent of tacrolimus in 1990, transplantation of the intestine began to emerge as therapy for intestinal failure. However, a high risk of rejection, with the consequent need for acute and chronic high-dose immunosuppression, has inhibited its widespread application. METHODS: During an 11-year period, divided into two segments by a 1-year moratorium in 1994, 155 patients received 165 intestinal allografts under immunosuppression based on tacrolimus and prednisone: 65 intestine alone, 75 liver and intestine, and 25 multivisceral. For the transplantations since the moratorium (n = 99), an adjunct immunosuppressant (cyclophosphamide or daclizumab) was used for 74 transplantations, adjunct donor bone marrow was given in 39, and the intestine of 11 allografts was irradiated with a single dose of 750 cGy. RESULTS: The actuarial survival rate for the total population was 75% at 1 year, 54% at 5 years, and 42% at 10 years. Recipients of liver plus intestine had the best long-term prognosis and the lowest risk of graft loss from rejection (P =.001). Since 1994, survival rates have improved. Techniques for early detection of Epstein-Barr and cytomegaloviral infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, and most recently allograft irradiation may have contributed to the better results. CONCLUSION: The survival rates after intestinal transplantation have cumulatively improved during the past decade. With the management strategies currently under evaluation, intestinal transplant procedures have the potential to become the standard of care for patients with end-stage intestinal failure.

Adult↗

Is the pathologic TNM staging system for patients with hepatoma predictive of outcome?

BACKGROUND: The pathologic TNM (pTNM) staging system was designed to aid in determining the prognosis of cancer patients and in planning and evaluating their treatment. The current pTNM classification system was not found to be predictive for patients undergoing orthotopic liver transplantation (OLTx) in the presence of hepatocellular carcinoma (HCC). Therefore, the authors examined the current system to determine whether improvements would allow the development of a more predictive system. METHODS: Three hundred seven patients with HCC underwent OLTx between 1981 and 1997. Risk factors for recurrence were identified using the Kaplan-Meier method with the log rank test. The Cox proportional hazards model was used to identify factors independently predictive of recurrence which were then used to create a new staging system. RESULTS: There was neither a direct correlation between the current pTNM system and tumor free survival nor homogeneity in outcomes for patients within certain current pTNM categories. Depth of vascular invasion, lobar distribution, lymph node status, and largest tumor size were found to be independent predictors of tumor free survival; tumor number was not found to be significant in multivariate analysis. A new staging system is proposed, which takes into account the results of the multivariate analysis in which tumor free survival correlates directly with stage. CONCLUSIONS: The proposed staging system is superior to the current pTNM staging system in predicting tumor free survival following OLTx with HCC. Further studies will determine the appropriateness of this system for staging HCC after subtotal hepatic resection.

Adolescent↗

Liver transplantation for hepatocellular carcinoma: a proposal of a prognostic scoring system.

BACKGROUND: The current staging system of hepatocellular carcinoma established by the International Union Against Cancer and the American Joint Committee on Cancer does not necessarily predict the outcomes after hepatic resection or transplantation. STUDY DESIGN: Various clinical and pathologic risk factors for tumor recurrence were examined on 344 consecutive patients who received hepatic transplantation in the presence of nonfibrolamellar hepatocellular carcinoma to establish a reliable risk scoring system. RESULTS: Multivariate analysis identified three factors as independently significant poor prognosticators: 1) bilobarly distributed tumors, 2) size of the greatest tumor (2 to 5 cm and > 5 cm), and 3) vascular invasion (microscopic and macroscopic). Prognostic risk score (PRS) of each patient was calculated from the relative risks of multivariate analysis. The patients were grouped into five grades of tumor recurrence risk: grade 1: PRS = 0 to < 7.5; grade 2: PRS = 7.5 to < or = 11.0; grade 3: PRS > 11.0 to 15.0; grade 4: PRS > or = 15.0; and grade 5: positive node, metastasis, or margin. The proposed PRS system correlated extremely well with tumor-free survival after liver transplantation (100%, 61%, 40%, 5%, and 0%, from grades 1 to 5, respectively, at 5 years), but current pTNM staging did not. CONCLUSIONS: 1) Patients with grades 1 and 2 are effectively treated with liver transplantation, 2) patients with grades 4 and 5 are poor candidates for liver transplantation, and 3) patients with grade 1 do not benefit from adjuvant chemotherapy.

Adolescent↗

Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence.

OBJECTIVE: To describe our experience with total hepatectomy and liver transplantation as treatment for primary hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) in children. STUDY DESIGN: A retrospective analysis of the perioperative course of 31 children with unresectable primary HBL (n = 12) and HCC (n = 19) who underwent transplantation between May 1989 and December 1998. Systemic (n = 18) and intraarterial (n = 7) neoadjuvant chemotherapy were administered; follow-up ranged from 1 to 185 months. RESULTS: For HBL, 1-year, 3-year, and 5-year posttransplantation survival rates were 92%, 92%, and 83%, respectively. Intravenous invasion, positive hilar lymph nodes, and contiguous spread did not have a significant adverse effect on outcome; distant metastasis was responsible for 2 deaths. Intraarterial chemotherapy was effective in all patients treated. For HCC, the overall 1-year, 3-year, and 5-year disease-free survival rates were 79%, 68%, and 63%, respectively. Vascular invasion, distant metastases, lymph node involvement, tumor size, and gender were significant risk factors for recurrence. Intraarterial chemotherapy was effective in 1 of 3 patients. Six patients died of recurrent HCC, and 3 deaths were unrelated to recurrent tumor. CONCLUSION: Liver transplantation for unresectable HBL and HCC can be curative. Risk factors for recurrence were significant only for HCC, with more advanced stages amenable to cure in the HBL group.

Adolescent↗

Should hepatomas be treated with hepatic resection or transplantation?

BACKGROUND: The aim of this collaborative study was to compare the long term results of hepatic resection (Hx) with those of orthotopic liver transplantation (OLTx) in large numbers of cirrhotic patients with hepatocellular carcinoma (HCC) and to delineate the roles of these two surgical treatments. METHODS: The databases of the National Cancer Center Hospital in Japan and the University of Pittsburgh Medical Center in the U. S. were exchanged and 294 cirrhotic patients who underwent curative Hx and 270 cirrhotic patients who underwent curative OLTx were selected for comparison. RESULTS: The mortality rate within 30 days and that within 150 days after Hx were significantly lower than those after OLTx (P = 0.001 and P = 0.00007, respectively). Overall survival was similar between the Hx group and the OLTx group (P = 0.40). When compared in the HCC patients without macroscopic vascular invasion and lymph node metastases, the overall survival rate after OLTx was significantly higher than that after Hx (P = 0.006). However, this difference was not significant between the patients with Child-Pugh Grade A tumors in the Hx group and all patients (majority with Child-Pugh Grade C tumors) in the OLTx group (P = 0.25). Tumor free survival after OLTx was significantly higher than that after Hx (P < 0.0001), particularly in HCCs measuring </=5 cm, unilobarly distributed tumors, and HCCs with either no or only microscopic vascular invasion. In HCCs measuring > 5 cm and those with macroscopic vascular invasion, the tumor free survival rate was similar between the Hx group and the OLTx group. CONCLUSIONS: In the face of organ shortage, HCC developing in a well compensated cirrhotic liver initially may be treated with Hx. However, the authors believe OLTx should be applied selectively to those patients with tumor recurrence and/or progressive hepatic failure.

Carcinoma, Hepatocellular↗

An analysis of pretransplantation variables associated with long-term allograft outcome in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy.

BACKGROUND: The present study analyzes pretransplantation variables associated with long-term liver allograft survival in 278 children who underwent transplantation under primary tacrolimus (FK506) therapy at a single center between October 1989 and October 1996. METHODS: The influence of 17 pretransplantation variables on long-term liver allograft outcome was analyzed. Donor variables included age, weight, gender, and cold ischemia time. Recipient variables included age, weight, gender, original liver disease, pretransplantation waiting time, previous abdominal surgery, United Network of Organ Sharing (UNOS) status, ABO blood group, bilirubin level, prothrombin time, ammonia level, creatinine level, and reduced-size/split liver grafts. RESULTS: Overall actuarial graft survival was 79.9% at 1 year, 79.1% at 2 years, and 78.3% at 3, 4, and 5 years. Retransplantation rate was 10.8%. Pretransplantation variables with a significant adverse effect on graft survival by univariate analysis were donor age < or = 1 year (P<0.004), donor weight < or = 10 kg (P<0.003), UNOS status I and II (P<0.007), ABO type O, B, and AB (P<0.03), and reduced-size/split liver grafts (P<0.02). Pretransplantation variables significant by multivariate analysis and therefore independent predictors of inferior graft outcome were donor weight '10 kg (relative risk [RR] 2.91, confidence interval [CI] 1.53-5.51); reduced-size/split liver grafts (RR 2.53, CI 1.30-5.64); and UNOS status I (RR 2.22, CI 1.11-4.43). CONCLUSIONS: Pediatric liver transplant recipients receiving primary tacrolimus therapy have long-term graft survival rates approaching 80%. UNOS status, donor weight, and the use of reduced-size/split liver grafts are the most important factors affecting survival.

Adolescent↗

Strategies to expand the donor pool for pancreas transplantation.

BACKGROUND: Our organ procurement organization has been forced to liberalize the donor criteria in order to expand the donor pool for pancreas transplantation. In this report, we describe our experience using whole organ pancreatic grafts from "marginal" donors, which include grafts obtained from donors over 45 years of age and from donors who were identified to be hemodynamically unstable at the time of organ retrieval. METHODS: A prospective study was performed between July 1994 and March 1998, during which time 137 pancreas transplants were performed at our center using organs procured by our own surgeons (organs sent by other teams were excluded). The rapid en bloc technique was used exclusively. The use of pancreatic grafts from marginal donors was analyzed for short-term and overall graft survival, and for delayed graft function and complications. RESULTS: Overall pancreas graft survival for our series was 83%, with a mean follow-up of 23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of whom were greater than 50 years of age. The actual graft survival rate of the over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically unstable donors on high-dose vasopressors. The actual graft survival in this group was 86%. There was no significant difference found in graft survival between recipients of pancreatic grafts from marginal and nonmarginal donors. Delayed graft function was exhibited by more recipients of grafts from donors on high-dose vasopressors (P<0.05), but this had no effect on long-term graft survival and endocrine function. Recipients of marginal donor grafts did not have higher rates of complication compared to recipients of nonmarginal grafts. CONCLUSIONS: Based on our results, we currently employ a graft selection strategy not limited by donor age or hemodynamic stability. Our selection of pancreas organs for transplantation is based on careful inspection of the pancreas and determination of the adequacy of the ex vivo flush. Our results suggest that the current pancreas donor pool may be expanded substantially.

Adolescent↗

Hyperbaric oxygen therapy for hepatic artery thrombosis after liver transplantation in children.

Early hepatic artery thrombosis (HAT) after pediatric orthotopic liver transplantation (OLT) can cause significant morbidity and mortality, leading to liver failure or septic complications requiring urgent retransplantation. Experimental evidence that hyperbaric oxygen (HBO) may ameliorate hepatic ischemic-reperfusion injury led to this study of HBO in pediatric liver transplant recipients who developed HAT. Children undergoing OLT under primary tacrolimus immunosuppression and University of Wisconsin organ preservation between August 1, 1989, and December 31, 1998, who developed HAT were the basis for this study. Patients who developed HAT between March 1, 1994, and December 31, 1998, were treated with HBO therapy until signs of ischemia resolved (absence of fever, normalizing liver injury test results) or for 2 weeks. The pediatric OLTs performed from August 1, 1989, to February 28, 1994, who developed HAT served as a control group. Primary outcome measures were survival, retransplantation rate, time to retransplantation, incidence of hepatic gangrene, and days to collateral formation. Three hundred seventy-five consecutive pediatric patients underwent 416 OLTs between August 1, 1989, and December 31, 1998. Thirty-one patients (7.5%) developed HAT at a mean time of 8.2 days (range, 1 to 52 days) post-OLT. In 17 patients, HBO treatment was begun within 24 hours of HAT or immediately after the revascularization attempt and performed twice daily for 90 minutes at 2.4 atmospheres pressure. Fourteen patients were treated without HBO. None of the HBO-treated patients developed hepatic gangrene. Eight HBO patients (47%) were bridged to retransplantation at a mean time of 157 days (range, 3 to 952 days) after initial OLT and all survived. Mean time to retransplant in the control group was 12.7 days (range, 1 to 64 days). HBO was well tolerated without significant complications. Although there was no significant difference in survival or retransplantation rates, HBO significantly delayed retransplantation, potentially by hastening the development of hepatic artery collaterals.

Arterial Occlusive Diseases↗

Factors impacting the survival of children with intestinal failure referred for intestinal transplantation.

PURPOSE: The aim of this study was to analyze factors impacting on the survival of pediatric patients with intestinal failure referred for intestinal transplantation (ITx). METHODS: Two hundred fifty-seven children (mean age, 3.4+/-0.26 years) with intestinal failure were evaluated for ITx between 1990 and 1998. All patients were dependent on total parenteral nutrition (TPN) for a mean of 31+/-2.7 months. The mean follow-up time from the date of evaluation was 9.2+/-0.9 months. RESULTS: Eighty-two (32%) children underwent ITx with a mean waiting time of 10.1+/-1.3 months (simultaneous liver-intestinal allograft in 68% instances). Of the 175 patients who did not undergo transplantation, 120 died, 23 were lost to follow-up, and 32 are alive. Younger patients (< or =1 year) had poorer survival rates than patients older than 1 year (P<.0001). The patients with the worse prognosis were those with necrotizing enterocolitis, and those with the best prognosis were those with Hirschsprung's disease. Patients with "surgical" causes had poorer survival rates than those with "nonsurgical" causes (P<.04). Patients with bridging fibrosis or established cirrhosis had an earlier mortality than patients with portal fibrosis (P<.003). The worst survival rate was found for patients with bilirubin levels of greater than 3 mg/dL (P<.0001), plateletcounts less than 100.000/mL (P<.0001), prothrombin time greater than 15 seconds (P = .03) or partial thromboplastin time greater than 40 seconds (P<.04). Children who at the time of evaluation needed only an isolated intestinal allograft had a better prognosis than those who required a combined liver-intestine allograft (P<.00001). With multivariate analysis independent prognosis risk factors of poor outcome were hyperbilirubinemia and severity of histopathologic damage. CONCLUSIONS: Early referral for ITx should occur before the development of liver dysfunction, taking into consideration the aforementioned risk factors that would facilitate the development and ominous evolution to liver failure.

Child, Preschool↗

Hepatic hemangioendothelioma: clinical experience and management strategy.

PURPOSE: This study sought to define management strategies based on clinical experience in treating infantile hepatic hemangioendothelioma. METHODS: A retrospective analysis of patients with hemangioendothelioma presenting to a tertiary liver transplantation center between 1989 and 1997 was performed. RESULTS: Thirteen patients (median age, 14 days) with hemangioendothelioma were identified. Congestive heart failure (P<.03) and abdominal mass (P<.081) were predictive of 5-month mortality rates. Ultrasonography and computerized axial tomography were the diagnostic modalities most commonly used. Treatment strategies consisted of medical management (steroids and alpha-interferon) and interventional modalities (hepatic artery ligation or embolization, resectional surgery, or orthotopic liver transplantation). Patients who underwent resectional surgery, with or without orthotopic liver transplantation, had a lower 5-month mortality rate (P<.02) and a greater 2-year survival rate (P<.003) than did those who underwent hepatic artery ligation or embolization. Early morbidity and mortality tended to be a consequence of the primary lesion, whereas late morbidity and mortality were reflective of the treatment modality used. CONCLUSIONS: In cases of failed medical management, resectional therapy should be used when possible. If partial hepatectomy is not technically achievable, hepatic artery embolization should be used either as definitive therapy or as a temporizing measure until orthotopic liver transplantation is possible.

Algorithms↗

Hepatobiliary malignancies. Primary hepatic malignant neoplasms.

Primary hepatic tumors are epithelial, mesenchymal, or mixed in origin. Of these, epithelial tumors are the most common and include hepatocellular carcinoma, cholangiocarcinoma, mixed hepatocholangiocarcinoma, hepatoblastoma, and a variety of more rare tumors. Hepatocellular carcinoma, also know as hepatoma or malignant hepatoma, is the most common, followed by cholangiocarcinoma. This article discusses these two malignancies.

Carcinoma, Hepatocellular↗