Search PubMed⌕ Search

Biomedical subjects

Enrico Benedetti

Publications and source records attributed to Enrico Benedetti.

At least 19 recordsLinked to original sources

'Prope' tolerance in a noncompliant living related small bowel transplant recipient after severe rejection.

Advances in immunosuppression and surgical technique have greatly improved patient outcomes after intestinal transplantation. However, the procedure remains one of the most challenging among solid organ transplantation as a result of the high rate of acute rejection, sepsis, and posttransplantation lymphoproliferative disorder. Recently, clinical trials to explore tolerance protocols in humans have been initiated, including small bowel transplant recipients, with results not always reproducible. The concept of operational tolerance is more meaningful in the clinical setting when physiological stability of graft function is achieved in the absence of maintenance immunosuppression. We report the intriguing case of a living related small bowel transplant recipient who developed clinical "prope" tolerance to the graft after treatment of severe acute rejection despite continuous noncompliance with immunosuppressive therapy.

Adult↗

Successful rescue of refractory, severe antibody mediated rejection with splenectomy.

Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

Adult↗

Human islet isolation outcomes from pancreata preserved with Histidine-Tryptophan Ketoglutarate versus University of Wisconsin solution.

This study was designed to compare Histadine-Tryptophan-Ketogluterate (HTK) with University of Wisconsin (UW) solution. Pancreata from extended criteria donors were flushed and transported with HTK (n=41) or UW (n=45). Isolation outcomes were determined by islet yields, viability and in vitro and in vivo function. Final yields were similar between two groups (HTK: 383,085 vs. UW: 328,514 EIN, P=0.14). In the HTK group, 63.4% (26/41) of isolations resulted in a yield of over 300,000, and in the UW group this was achieved in 46.7% (21/45; P=0.12). Viability results were similar (HTK: 82.9 vs. UW: 82.7%, P=0.93). Stimulation index in the HTK and UW groups were comparable (5.28 vs. 4.91, P=0.62). Ten out of 41 islet preparations in HTK and 4 of 45 in UW group were suitable for clinical transplantation (P=0.05). Our study shows HTK is equivalent to UW solution in the preservation of pancreata for islet isolation.

Adenosine↗

Electron-beam CT as a diagnostic modality in pediatric nephrology and renal transplant surgery.

Electron-beam computed tomography is an imaging technology with a variety of medical applications, primarily in cardiology due to its sub-second acquisition time enabling visualization of a beating heart. Recently, this technique has also been introduced into other fields because of lower radiation exposure compared to traditional computed tomography, as well as the strengths of post-procedural three-dimensional visualization. This report evaluates electron-beam computed tomography as a diagnostic modality in pediatric nephrology patients. Seven patients reflecting typical clinical scenarios in pediatric nephrology were reviewed with regard to the value of electron-beam computed tomography and its contribution to the diagnostic workup. Electron-beam computed tomography is noninvasive and allows three-dimensional post-processing, enabling highly accurate images while requiring less radiation and acquisition time. It is very useful for clinical questions that require a detailed description of vascular and renal anatomy.

Adolescent↗

Hilar early division of the hepatic duct in living donor right hepatectomy: the probe-and-clamp technique.

The division of the hepatic duct is one of the most challenging passages of the donor hepatectomy. We report our experience with the early division, prior to the liver parenchyma resection, of the hepatic duct and the definition of the biliary anatomy with a probe inserted in the proper hepatic duct. From February 2002 to December 2004, 40 donors (25 male, 15 female; mean age 34, range 20-57) underwent right hepatectomy. The yield was a single duct in 24 donors (60%), two ducts in 12 donors (30%), and three ducts in one donor (2.5%), and three donors had aberrant anatomy yielding two ducts (7.5%). By means of a ductoplasty, a single orifice for the recipient biliary anastomosis was obtained in 77.5% of the cases. Three donors (7.5%) suffered a resection surface bile leak. The technique of hepatic duct probing and early division provides a precise definition of the biliary anatomy and facilitates one of the most challenging passages of the donor hepatectomy. This technique should also contribute to maximizing the preservation of the vascular supply of the hepatic duct and the yield of a single orifice for the recipient anastomosis. At a median follow-up of 21 months (range 10-44), neither short- nor long-term complications had been caused by the small donor choledochotomy.

Adult↗

Living related segmental bowel transplantation: from experimental to standardized procedure.

INTRODUCTION: Living donor bowel transplantation has recently emerged as a valuable alternative to cadaver bowel transplant. We herein present our single-center experience with this procedure. MATERIALS AND METHODS: From April 1998 to October 2004, 12 living donor intestinal transplants were performed in 11 patients (7 males, 4 females; average age, 26 years). Four of the patients were children under 5 years. A segment of distal ileum 150 to 180 cm long in pediatric recipients and 200 cm long in adult was used. The immunosuppressive protocol consisted of induction with thymoglobulin and maintenance with tacrolimus with or without mycophenolate mofetil and steroids. RESULTS: All donors recovered well and did not experience any early or late complications. The overall 1- and 3-year patient survival was 82% with a graft survival of 75%. In the last 8 patients, transplanted after January 2000, the 1-year patient and graft survival has been 100% and 88%, respectively. The median hospital stay was 36 days (range, 13-290 days). During the first year after transplant only, the patient who received a totally mismatched graft experienced one episode of rejection (8%). All the surviving patients are currently supported by enteral diet without fluid requirements. CONCLUSIONS: Living donor bowel transplantation is a valuable strategy in the treatment of irreversible intestinal failure. The results have improved over the years thanks to increased experience of the team.

Adult↗

Pattern of growth after pediatric living-donor small bowel transplantation.

The aim of our study was to analyze growth in children who underwent LDSB. The question was whether these children obtain linear growth and improvement of the Z-score for height and weight after the transplant. Three children with a mean age of 24 months underwent living-donor intestinal transplantation with 150 cm of terminal ileum. At a mean follow-up of 27 months height increased from 82.5 to 97.5 cm although Z-score for height did not improve, -2.679 to -2.675. Mean weight increased from 11.4 to 14.2 kg while Z-score for weight went from -1.916 to -2.409. Although these data are pertinent to only three children and the follow-up is slightly longer than two yr, it appears that while long-term survival and independency from TPN is achieved, only linear growth might be expected and catch-up growth does not occur.

Body Height↗

Routine left robotic-assisted laparoscopic donor nephrectomy is safe and effective regardless of the presence of vascular anomalies.

The classic approach to donor nephrectomy consists of preferential procurement of the kidney without vascular anomalies. We studied the effect of routine procurement of the left kidney regardless the presence of multiple arteries on the outcomes of robotic-assisted laparoscopic living donor nephrectomy (LLDN) with particular reference to the incidence of urological complications. From August 2000 to July 2005, 209 left LLDNs were performed. We analyzed the outcomes of donors and recipients in relation to the presence of multiple vessels versus normal anatomy. We divided the patients into two groups: group A (n = 148) with normal vascular anatomy and group B (n = 61) with vascular anomalies. In the donors, no significant difference in conversion to open surgery rate, blood loss, length of stay, was noted between the two groups; operative time and warm ischemia time were slightly higher in group B. One-year patient survival was 98% in both groups while the 1-year graft survival was 96.6% in group A and 96% in group B. Only one urological complication was noted in the group with normal anatomy (0.7%) versus none in the group with multiple arteries. Left kidney procurement using robotic-assisted laparoscopic technique is safe and effective, even in the presence of vascular anomalies.

Adolescent↗

Successful identical-twin living donor small bowel transplant for necrotizing enterovasculitis secondary to Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis with unknown etiology. Extra-pulmonary manifestations of CSS are currently treated with a combination of steroids and Cyclophosphamide. Its gastrointestinal complications may be devastating, occasionally requiring extensive bowel resection resulting in short-gut syndrome. Living-related small bowel transplantation (LRSBTx) is a relatively standardized procedure that, not only represents a valid alternative to cadaver bowel transplant in selected cases, but also portraits excellent results when performed in experienced centers. The availability of an identical twin as a donor, which allows avoidance of immunosuppressive therapy, is a major indication for this procedure. We present the case of a young individual affected by gastrointestinal necrotizing vasculitis that lost almost his entire small bowel requiring the immediate institution of total parenteral nutrition (TPN). However, within few weeks a significant hepatic dysfunction ensued. An identical twin-brother, not affected with CSS, became an immediate, optimal donor-candidate for LRSBTx, the first of this kind in a patient affected with CSS. Following the procedure, two main concerns were addressed: the recipient's ability to recover a regular intestinal function without immunosuppression and the possible recurrence of the primary disease. Twenty-seven months post-transplant, the patient enjoys a regular lifestyle without any clinical, endoscopic and histologic evidences of recurrent disease in the transplanted graft.

Adult↗

Peliosis hepatis in a living related liver transplantation donor candidate.

Peliosis hepatis is a rare benign condition histologically characterized by multiple cystic blood-filled spaces distributed throughout the liver parenchyma. Peliosis hepatis has been associated with malignancies, immunosuppression, infections and medications. We report a case of peliosis hepatis in a candidate for living liver donation, which regressed with restitutio ad integrum, after the noxious stimulus was stopped. We conclude that after diagnosis of peliosis hepatis is established and its cause is removed, simple radiographic imaging is sufficient to document the restitutio ad integrum of the parenchyma, avoiding repeat histological confirmation.

Adult↗

Combined living donor liver/small bowel transplantation.

We are reporting the first known case of sequential combined living donor liver/small bowel transplantation (LDL/SBT). A 2-year-old boy born with gastroschisis and intestinal malrotation lost his entire small bowel and colon shortly after birth. He underwent a living donor small bowel transplant at 1 year of age that was lost 4 months after implantation for posttransplant lymphoproliferative disease (PTLD). He recovered from PTLD but developed total parenteral nutrition (TPN)-induced liver failure. He received a combined left lateral liver and terminal ileum transplant that we chose to perform sequentially due to the presence of preformed antibodies against his mother's tissues. The mother had no complications and a cumulative hospital stay of 7 days. At 9 months postsurgery, the patient is on full enteral nutrition and has suffered neither technical complications nor rejection. The technique described here is reproducible and makes combined living donor LDL/SBT an alternative to combined cadaveric liver-small bowel transplant.

Child, Preschool↗

Islet transplantation: current status and future directions.

Pancreatic islet transplantation has gone a long way to finally enter the armamentarium of today's clinicians for the battle against diabetes. The proof of principle has been made and current clinical islet transplant trials need to further refine this attractive treatment modality. We review the post-Edmonton era, the selection of islet transplant recipients, the production of islet grafts, and the need for immunosuppression and procedure-related risks. The success of islet transplantation and expansion of clinical trials with islet networks are also discussed.

Clinical Trials as Topic↗

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients.

Patients with hepatocellular carcinoma who undergo orthotopic liver transplantation (OLT) are at risk for post-transplant tumor recurrence. The aim of this study was to evaluate whether expression of p53 and Ki-67 in hepatocellular carcinoma lesions present in explanted liver tissue was associated with time to tumor recurrence after OLT. Subjects consisted of 20 consecutive patients who underwent OLT and were found to have hepatocellular carcinoma in the liver explant. Immunostaining for p53 and Ki-67 was performed by standard methods. The presence of nuclear immunostaining in >10% of the tumor tissue was considered positive. Time to recurrence of hepatocellular carcinoma after OLT was compared between patients with positive and negative immunostaining by the log rank test. Multivariate analysis was performed using a Cox regression model to control for potentially confounding clinical factors. Time to post-transplant hepatocellular carcinoma recurrence was significantly more rapid in p53+ (P=0.0007) and Ki-67+ cases (P=0.001). These associations remained significant in multivariate analysis. Furthermore, time to recurrent hepatocellular carcinoma was significantly shorter in patients with a serum alpha feto-protein (AFP) level >or=100 ng/ml at time of diagnosis, compared to those with an AFP level <100 ng/ml (P=0.003). In conclusion, expression of p53 and Ki-67 in hepatocellular carcinoma lesions, and a serum AFP level >or=100 ng/ml were associated with more rapid recurrence of hepatocellular carcinoma after OLT. Identification of patients at risk for early post-transplant recurrence could be used to guide surveillance and adjuvant treatment strategies.

Biomarkers, Tumor↗

Concomitant clotrimazole therapy more than doubles the relative oral bioavailability of tacrolimus.

The purpose of this pharmacokinetic study was to determine whether the relative oral bioavailability of tacrolimus is increased with concomitant administration of clotrimazole. Pharmacokinetic studies were conducted in 6 adult kidney transplant patients receiving tacrolimus therapy. Pharmacokinetic profiling was performed by blood sampling over 12 hours before and after the administration of a 5-day course of clotrimazole. Tacrolimus whole-blood concentrations were determined by microparticle enzyme immunoassay. Noncompartmental pharmacokinetic analysis was conducted using WinNonLin, Standard Edition, Version 1.1. Concomitant administration of clotrimazole more than doubled the relative oral bioavailability of tacrolimus. The mean AUC0-12 of tacrolimus was increased 250% with clotrimazole (467.0 +/- 170.0 ng.h/mL versus 188.7 +/- 50.2 ng.h/mL; P = 0.002). Tacrolimus blood trough concentrations also more than doubled with coadministration of clotrimazole (27.7 +/- 10.4 ng/mL versus 11.6 +/- 4.0 ng/mL; P = 0.003). Mean Cmax was significantly increased with clotrimazole (70.7 +/- 34.7 ng/mL versus 27.4 +/- 11.1 ng/mL, P = 0.01). Tmax decreased from 3.2 +/- 1.6 hours to 1.9 +/- 1.0 hours (P = NS). In addition, the apparent oral clearance decreased 60% with coadministration of clotrimazole (median oral clearance 0.16 L/h/kg versus 0.40 L/h/kg; P = 0.03). Thus, clotrimazole causes a significant increase in the relative oral bioavailability, Tmax, and trough concentration of tacrolimus. Tacrolimus levels should be monitored following initiation or discontinuation of clotrimazole to minimize toxicity or precipitation of an acute rejection episode due to subtherapeutic levels.

Adult↗

Standard chronic immunosuppression after kidney transplantation for systemic lupus erythematosus eliminates recurrence of disease.

BACKGROUND: There is only limited experience in patients with systemic lupus erythematosus (SLE) with drugs that have developed for immunosuppression after organ transplantation, namely calcineurin inhibitors (CI). The aim of this study is to determine the effect of these drugs on disease activity after kidney transplant in patients affected by SLE. METHODS: Between January 1990 to March 2003, 13 patients with end- stage renal disease secondary to SLE received 14 kidney transplants. The outcome variables assessed include graft and patient survival as well as clinical and serological lupus activity. RESULTS: All received CI-based immunosuppression (cyclosporine or tacrolimus). Actuarial patient and graft survivals at 5 yr were 100 and 93%, respectively. Recurrence of clinical or serological disease was never detected. CONCLUSIONS: To date, only anecdotal experience with CI in the treatment of SLE has been reported. The favorable response observed in our patients suggests that CI at low-doses are effective in preventing SLE-reactivation. Further studies focused on calcineurin inhibitor treatment in SLE patients who fail to respond to standard medical management should be conducted.

Adult↗

Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients.

Sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart-lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. Sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving.

Bronchoscopy↗

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury.

BACKGROUND: Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients. PATIENTS AND METHODS: Twenty-two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD x2 doses or no TG. No differences in recipients' demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re-vascularization. Post-operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non-function and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non-function and no need for re-transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post-reperfusion) of TG group demonstrated a trend for increased central ballooning. CONCLUSION: The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post-reperfusion are underway.

Adult↗