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Biomedical subjects

A G Tzakis

Publications and source records attributed to A G Tzakis.

At least 19 recordsLinked to original sources
PubMed2007

Ten-year experience in porto-caval hemitransposition for liver transplantation in the presence of portal vein thrombosis.

Porto-caval hemitransposition (PCH) in liver transplantation allows revascularization of the liver when the porto-mesenteric axis is thrombosed. We, here, review our experience over an 11-year period. A total of 23 patients underwent liver transplantation using PCH. Immunosuppression was based on tacrolimus, with sirolimus used in case of renal insufficiency. Most common diagnoses were hepatitis C, Laennec's, Budd-Chiari and cryptogenic cirrhosis. Six patients needed splenectomy prior to transplant, 5 during transplant, 1 post-transplant, 11 had no splenectomy. Overall survival was 60% at 1 year and 38% at 3 years, with 10 of 23 patients currently alive and the longest survivor at 9.3 years. Most common cause of death was sepsis/multisystem organ failure, followed by pulmonary embolism. A total of 7/23 patients experienced post-operative gastrointestinal bleeding episodes, 6/23 patients developed thrombosis of the vena cava (median 162 days post-op). Post-operative ascites was noted in almost all patients. Renal dysfunction was commonly seen even after the first month post-transplant. PCH offers a feasible option for liver transplantation in those patients with complex thrombosis of the mesenteric and portal circulation.

Adult↗
PubMed2006

Zoom endoscopic monitoring of small bowel allograft rejection.

BACKGROUND: The small bowel has been successfully transplanted in patients with irreversible intestinal failure. This report aims to describe endoscopic monitoring of small bowel rejection. METHODS: A magnification endoscope (zoom endoscope) was used in this study. In the first part of the study (October 1998 to March 2000, 271 endoscopy sessions), the specific endoscopic findings that correlated with rejection were determined. An analysis then was performed on data from the second period (March 2001 to November 2002, 499 sessions) to evaluate the zoom endoscope's accuracy in monitoring rejection. RESULTS: Specific endoscopic findings of rejection found in the first period included background erythema, villous congestion, blunted villous tip, and shortened villous height. When the rejection was successfully treated, endoscopic appearance returned to normal. On the basis of these findings, five endoscopic criteria (villous shortening, villous blunting, background erythema, villous congestion, and mucosal friability) were used to score endoscopic sessions in the second period. Endoscopic diagnosis of rejection was compared with histology. Adult patients showed a sensitivity of 45%, a specificity of 98%, a positive predictive value of 82%, and a negative predictive value of 88%. In pediatric patients, these values were, respectively, 61%, 84%, 57%, and 86%. On 59 distinct occasions (30 in period 1 and 29 in period 2) in which the results were endoscopy negative yet biopsy positive (mild) for rejection, we elected not to treat these rejections on the basis of clinical evaluation, and 58 (98%) resolved without further therapy. CONCLUSIONS: With the use of magnification, endoscopy is a useful tool for monitoring acute rejection in the small bowel allograft.

Adolescent↗
PubMed2006

The impact of nonalcoholic fatty liver disease and the metabolic syndrome on progression of fibrosis in patients with recurrent HCV after liver transplantation.

Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have been shown to play a role in disease progression and response to therapy in patients with chronic hepatitis C virus (HCV) infection. The primary objective of this study was to evaluate the impact of coexisting NAFLD and MS on the progression of fibrosis in patients with recurrent HCV treated with interferon (IFN)/ribavirin after orthotopic liver transplantation (OLT). From 1998 to 2004, a total of 418 patients underwent OLT in our center for HCV-related cirrhosis. Thirty-five patients with recurrent HCV on IFN/ribavirin treatment, who had at least 2 posttransplant liver biopsies at least 6 months apart, were included in the study. Patients who had MS at the time of their first posttransplant biopsy were identified. The first and last posttransplant biopsies were assessed for the presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The fibrosis progression rate (FPR) was calculated and expressed in fibrosis units per month (FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first posttransplant biopsy. The mean FPR was 0.05+/-0.16 FU/mo in the presence of NAFLD compared to 0.07+/-0.10 FU/mo in its absence (P=.68) and 0.03+/-0.06 FU/mo in the presence of MS versus 0.10+/-0.15 FU/mo in its absence (P=.06). When FPR values were divided into two categories of <0.16 FU/mo or >or=0.16 FU/mo (below/above the 25% upper quartile) or <0.08 FU/mo or >or=0.08 FU/mo (below/above the 50% upper quartile), there was no correlation between FPR categories and the presence of NAFLD with or without MS, only MS, or the absence of both in the first liver transplant biopsy (P=.13). Coexisting NAFLD or MS had no significant effect on the progression of fibrosis after OLT in patients with treated hepatitis C after OLT.

Adult↗
PubMed2006

Refractory ascites after liver transplantation: an analysis of 1058 liver transplant patients at a single center.

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.

Adolescent↗
PubMed2006

Liver and intestine transplantation in the United States, 1995-2004.

Three years of survival data are now available and the impact of the model for end-stage liver disease (MELD) allocation system is becoming clear. After a decline in new registrants to the waiting list in 2002, the number increased to 10 856 new patients in 2004. Since the implementation of MELD, the percentage of patients who have been on the list for 1-2 years has declined from 24% to 19%. There has been a shift upward in the percentage of patients with higher MELD scores on the waiting list. An increasing percentage of adult living donor liver recipients are over the age of 50 years; from 1% in 1997 to 51% in 2004. Parents donating to children (93% of living donors in 1995), represented only 14% in 2004. Long-term adjusted patient survival declined with increasing recipient age in adults following either DDLT or LDLT. Cirrhosis caused by chronic hepatitis C virus (HCV) is the leading indication for liver transplantation and is associated with reduced long-term survival in recipients with HCV compared to those without HCV, 68% at 5 years compared to 76%. Although the intestine waiting list has more than doubled over the last decade, an increasing number of centers now perform intestinal transplantation with greater success.

Adolescent↗
PubMed2005

Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative Campath-1H exposure.

A number of recent reports in clinical and experimental intestinal transplantation have suggested that the donor lymphocytes present in and around the gastrointestinal system are potent mediators of graft-versus-host (GvH) reactivity and that GvH responses may contribute to posttransplant morbidity. Therefore, we have tested the proliferative and cytotoxic capabilities of gut-associated lymphocytes from cadaveric donors obtained prerevascularization (pre-r) and about 6 hours postrevascularization (post-r) in recipients pretreated with Campath-1H antibody (alemtuzumab). Mixed lymphocyte reactions (MLR) were performed with lymphoid cells isolated from intestinal epithelial mucosa, lamina propria, and lymph nodes. The pre-r lymphocytes responded strongly to both the recipient and third-party alloantigenic stimulating cells. However, similar preparations from the post-r samples responded in MLR at significantly lower levels (P < .01). This post-r decrease in responsiveness was not observed in similar lymphocyte samples obtained from donors of recipients not treated with Campath-1H. Both the pre-r and post-r samples had similar flow cytometric profiles, suggesting that there was no receptor loss in these lymphoid tissues by the short-term 6-hour exposure to Campath-1H given to the recipient. Conversely, in preliminary experiments where the donor were treated with Campath-1H, it was observed that very few lymphocytes could be obtained from intestinal tissues (n = 3). These results suggested that Campath-1H treatment of the recipient could bring about a drastic reduction in an otherwise strong GvH reactivity by the donor intestinal immune cells.

Alemtuzumab↗
PubMed2005

The impact of Campath 1H induction in adult liver allotransplantation.

BACKGROUND: We report our experience with Campath 1H in adult liver allotransplantation. METHODS: Between December 2001 and February 2004, 77 patients underwent liver transplantation using Campath 1H induction and low-dose maintenance tacrolimus immunosuppression. The control group consisted of 50 patients with similar baseline characteristics and the same eligibility criteria, transplanted under our standard Tacrolimus/steroids regimen. Hepatitis C patients were excluded from the study. RESULTS: Patient and graft survival were similar for both groups. The incidence of rejection was significantly lower in the Campath vs the control group (51% vs 65% at 12 months, P = .009). Tacrolimus trough levels and conversion from Tacrolimus or the addition of other immunosuppressive drugs due to nephrotoxicity were also significantly lower in the Campath 1H group. CONCLUSION: Campath 1H induction with low-dose Tacrolimus maintenance immunosuppression is an effective regimen in reducing acute rejection in adult liver transplantation, while maintaining lower tacrolimus levels and less nephrotoxicity than our conventional immunosuppressive regimen.

Adult↗
PubMed2005

Transplantation for the treatment of intra-abdominal fibromatosis.

MATERIALS AND METHODS: During the last 9 years we treated 14 patients with a diagnosis of intra-abdominal fibromatosis. The 11 patients who received an intestinal allograft included isolated intestine (n = 6), liver-intestine (n = 1), intestine-kidney (n = 1), multivisceral (n = 1), multivisceral-kidney (n = 1), multivisceral-no liver (n = 1). Three patients received an intestinal autograft after partial abdominal evisceration and ex vivo tumor resection. Three patients additionally underwent an abdominal wall allograft. RESULTS: At follow-up until August 2004, all autotransplant patients are alive. Four intestinal transplant patients died within the first postoperative month. There were three graft losses. A patient who lost his graft early postoperatively was retransplanted but died of sepsis shortly there after. Two more patients lost their graft due to severe rejection and were retransplanted successfully. Two patients developed desmoid tumor recurrence in their abdominal or thoracic wall. Ten patients are alive 1 to 9 years posttransplantation. Nine have fully functioning grafts and one patient requires TPN supplementation at night due to dysmotility of her autograft. CONCLUSION: Intestinal allo-, or autotransplantation combined with transplantation of the abdominal wall can be lifesaving for patients suffering from extensive intra-abdominal fibromatosis.

Fibromatosis, Abdominal↗
PubMed2004

Trends in serum citrulline and acute rejection among recipients of small bowel transplants.

A test for detecting acute cellular rejection (ACR) of small intestinal transplants (ITx) would be a major advance. Small preliminary studies suggest that serum citrulline levels correlate with ACR. The results for a group of 26 isolated intestinal and multivisceral transplant recipients are summarized here. Serum citrulline concentrations were determined by ion exchange chromatography and compared to biopsy-based grade of ACR. Other factors considered included patient and donor age and sex, ischemia time, and serum creatinine. Straight-line fits were employed to describe how each patient's citrulline levels changed over time. Estimated times to achieve normal citrulline (>or=30 micromol/L) ranged from 1 to 730 days posttransplant for 21 patients demonstrating increasing citrulline levels over time. Using stepwise linear regression, patients' ranks for time required to achieve normal citrulline levels were the only independent predictors of both maximum ACR (P <.0001) and average ACR (P =.0059) after 14 days posttransplant. The rate and direction of change in citrulline over time may be an indicator of the risk of acute rejection. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.

Adult↗
PubMed2004

Viral interleukin-10 gene therapy to induce tolerance to solid organ transplants in mice.

In this study, a novel gene therapy approach to prolong allograft survival was designed. Autologous (syngeneic) hematopoietic stem cell-enriched bone marrow cells (HSC; lin(-)) engineered with the vIL-10 gene (vIL-10-HSC) were injected (4 to 6 x 10(6) cells, i.v.) into lethally (9.5 Gy) or sublethally (4 Gy) irradiated CBA/J mice 6 weeks prior to allogeneic heart (C57BL/6) transplantation (Tx). Cardiac allograft survival was significantly (P <.004) prolonged in lethally (71 +/- 40 days) and sublethally (114 +/- 15 days) irradiated mice that received vIL-10-HSC compared to controls that received no HSC (11 +/- 1 days), unengineered HSC, or vector-DNA-engineered HSC (12 to 16 days). Tolerant graft histopathology demonstrated mild arteritis/venulitis (grade 0.7) and rejection (grade 1.0). Intragraft expression of costimulatory molecules (B7.1, B7.2), cytokines (IL-2, IL-4, mIL-10, IFN-gamma), and iNOS molecules were markedly lower in tolerant grafts that survived for >100 days; recipient T lymphocytes demonstrated hyporeactivity to donor and third-party antigens in mixed lymphocyte cultures. These findings have important implications and potential therapeutic applications in transplantation and autoimmune diseases.

Animals↗
PubMed2004

Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation.

Surgical principles and techniques derived from organ transplantation surgery can provide novel applications in general surgery. We present an update on our 5-year experience with intestinal autotransplantation and abdominal wall transplantation. Nine patients underwent intestinal or multivisceral transplantation with the addition of 10 abdominal wall grafts to cover the large open areas from previous surgeries. Seven patients underwent near-total abdominal evisceration, ex vivo resection of masses at the base of the mesentery, followed by intestinal autotransplantation; 44% of the abdominal wall graft recipients are alive, but none of the fatalities were related to the graft itself. In two cases the graft had to be removed due to venous thrombosis. Of patients with intestinal autotransplants, 71% are alive with two mortalities due to recurrent metastatic malignancy. In only one case, the intestinal autograft had to be removed because of venous thrombosis. All surviving patients but one are on a regular diet; two are on supplemental enteral feeds. These results show that anastomotic and resection techniques derived from the experience in solid organ transplant can be utilized in complex wound closure, as is the case of abdominal wall transplantation, or resection of large retroperitoneal tumors with intestinal autotransplantation.

Abdominal Wall↗
PubMed2004

Factors affecting metabolic and electrolyte changes after reperfusion in liver transplantation.

BACKGROUND: The metabolic and electrolyte changes were evaluated after various durations of cold and warm ischemia times to correlate ASA status with hemodynamic changes that may affect the severity of the reperfusion syndrome. PATIENTS AND METHODS: Sixty-one patients who underwent liver transplantation (OLT) were monitored by arterial pH, PaO2, PaCO2, HCO2, BE, K+, Ca2+, Na+, GL, and serial Ht at three specific times: after the skin incision (baseline), 10 minutes before reperfusion (T2), and 10 minutes after reperfusion (T3). Changes in metabolic parameters were correlated with ASA status, hemodynamic changes, time of OLT, as well as cold and warm ischemia times. RESULTS: The pH in ASA IV patients was significantly lower at T1 and T3, and PCO2 higher in ASA V at T1. A significant correlation was observed between pH, PaCO2, HCO3-, BE, Na+, Ca2+, and glucose with the phase of the procedure. The pH and HCO3- decreased significantly from T1 and T2, increasing during T3. Ca2+ fell from T1 to T2 increasing in T3. Mean glucose and sodium levels increase from T1 to T3. Mean BE dropped from T1 to T2 and increased at T3 without a significant correlation between the metabolic parameters in any phase of the study and the cold or warm ischemia times. Patients with a high ASA status showed an increased risk for cardiovascular collapse after reperfusion. CONCLUSIONS: Patients with advanced ASA status are more prone to metabolic and acid-base disturbances during reperfusion, without any relation to the cold or warm ischemia times. High ASA status shows an increased risk for cardiovascular collapse after reperfusion.

Adult↗
PubMed2003

Sirolimus therapy in orthotopic liver transplant recipients with calcineurin inhibitor related chronic renal insufficiency.

UNLABELLED: Calcineurin inhibitor-related renal toxicity affects patient and graft survival in transplant recipients. Our clinical experience has revealed sirolimus to be an effective agent in treating renal insufficiency related to calcineurin inhibitor toxicity. METHODS: We performed a retrospective review of the medical records of OLT recipients suffering from chronic renal insufficiency and treated with sirolimus at the University of Miami. RESULTS: Fourteen patients (nine men and five women) of mean age 57 years who had been treated with tacrolimus for at least 30 days were converted to sirolimus after developing nephrotoxicity. Mean creatinine clearances collected on day 0, 30, 60, and 90 after conversion were 40.1 mL/min, 49.6 mL/min, 53.9 mL/min, and 51.4 mL/min, respectively. Episodes of acute cellular rejection were not increased during the sirolimus conversion. CONCLUSION: This retrospective review suggests that OLT patients suffering from tacrolimus-related renal insufficiency successfully converted to sirolimus may benefit from this therapy.

Creatinine↗
PubMed2003

Preservation injury patterns in liver transplantation associated with poor prognosis.

Preservation injury (PI) is defined as hepatic dysfunction that occurs within 10 days of liver transplantation (OLT) but spontaneously resolves. However, we noted two new patterns: one characterized by histologic evidence of preservation injury that occurs at later than 10 days post-OLT (late PI), and a second, of persistent charge in liver biopsies > 10 days post-OLT (persistent PI). To characterize these new patterns, we performed a retrospective study of patients who underwent liver biopsies for hepatic dysfunction post-OLT from September 1993 to March 1998. The outcome of the 61 patients with preservation injury on liver biopsy after OLT was followed until the last clinic visit or death. Thirty patients had early PI, 16 patients had persistent preservation injury and 15 patients, late onset preservation injury. There were no significant differences in the age (P =.28), sex (P =.77), follow-up time (P =.78), cold ischemia (P =.3), or warm ischemia time (P =.16) between these groups. There was also no significant association between early preservation injury or persistent preservation injury with the development of acute or chronic rejection (P =.19). The overall survival rates at 1, 3, and 5 years was 52%, 45%, and 45%, respectively. There was no significant difference in survival between early, persistent, and late PI patterns (P =.59), although there was a trend toward better survival for patients with early preservation injury. The survival of OLT patients with persistent or late preservation injury is poor and should prompt consideration for retransplantation.

Adolescent↗
PubMed2003

Ten years of sirolimus therapy in orthotopic liver transplant recipients.

BACKGROUND: Sirolimus therapy has been used in orthotopic liver transplant (OLT) recipients diagnosed with a variety of diseases; chronic graft rejection (CR), calcineurin associated renal toxicity, preemptive immune suppression, calcineurin related neurotoxicity, preemptive therapy in transplant recipients with history of hepatocellular carcinoma, and steroid resistant allograft rejection. METHODS: A search for the medical literature and experiences involving sirolimus was done. RESULTS: Several animal and human reports evaluating the use sirolimus in liver transplant recipients are found and discussed. CONCLUSION: Sirolimus has been used for multitude of indications, primarily based on anecdotal experiences. However, reports of sirolimus related side effects have decreased the transplant communities' enthusiasm towards promoting this agent as a safe immune suppression agent.

Creatinine↗
PubMed2003

Intestinal transplantation: advances in immunosuppression and surgical techniques.

Campath-1H is being used as induction immunosuppression for intestinal/multivisceral transplantation. Patient and graft survival in this preliminary experience is similar to previous studies but there has been a significant decrease in the incidence and severity of acute rejections without increase of opportunistic infections. Collage of the abdominal wall (transplantation of a composite graft of the abdominal wall) can provide biologic coverage of the newly transplanted abdominal organs if necessary. Partial abdominal exenteration, ex vivo resection, and intestinal autotransplantation may be useful in removing otherwise unresectable lesions of the root of the mesentery.

Graft Rejection↗