Biomedical subjects

D Weppler

Publications and source records attributed to D Weppler.

At least 55 records · Page 3Linked to original sources

PubMed1997

Donor biliary variations: an overlooked problem?

Documented causes of biliary complications following orthotopic liver transplantation have been related to technical imperfections or insufficient arterial supply. Although anatomical variations of the extrahepatic biliary system are not infrequent, neither their incidence, surgical management nor possible association with complications have been reported in liver transplantation. At our institution, the global incidence of biliary complications following 357 consecutive liver transplants performed in 324 patients over a 2-yr period was 15.4% (55/357). Anomalous donor extrahepatic ducts were verified in 10 cases (2.8%) and they were recognized intraoperatively, prior to biliary reconstruction, in 7 cases. Technical complications occurred in 1 of these 7 and in 3 other cases where the anomalous ducts were not identified until later in the postoperative period when serious clinical problems ensued. We herein present a description of these 10 cases, with reference to the techniques employed to manage the anatomical anomalies and to treat complications. As in any hepatobiliary procedure, awareness of possible variations of the extrahepatic biliary system, intraoperative identification of the anomalous ducts and appropriate tailoring of the surgical technique are advisable in order to avoid serious postoperative complications in liver transplantation.

Adult↗

PubMed1996

Routine use of the piggyback technique in pediatric orthotopic liver transplantation.

The theoretical advantages of the piggyback technique over conventional orthotopic liver transplantation are as follows. (1) Continuous venous decompression during the anhepatic phase is provided without venovenous bypass. (2) Warm ischemia time can be shortened because there is no need for the infrahepatic vena cava anastomosis. The following report is a review of the authors' experience with this method in children during the past year at their institution. Analyses of intraoperative hemodynamics and blood loss, postoperative renal function, patient and graft survival, and length of hospital stay have shown excellent results. There were no intraoperative deaths, and causes of death and graft loss were not related to the technique. The authors conclude that children who undergo liver transplantation can be very satisfactorily managed with the piggyback operation, and this technique may be more advantageous than the conventional method.

Adolescent↗

PubMed1996

Status of liver and gastrointestinal transplantation at the University of Miami.

The liver transplant program at the University of Miami, established in 1987, was rejuvenated in June 1994 with the addition of new staff and expanded to include all organs of the gastrointestinal tract. Since its inception, 630 patients have been transplanted in the program. During the past 2 years we performed 349 transplants in 318 patients (livers n = 323 in 298 patients, liver + kidneys n = 13, liver + islet n = 10, liver + kidney + islets n = 1, liver + heart n = 10, liver + lung n = 1). These included 4 split-liver, 3 living-related, multiple reduced-sized and one "Domino" liver transplant. We have an active pediatric program and 10% of our transplanted patients are pediatric. Our overall patient and graft survival rates were 81% and 78%, respectively. The intestinal transplant program was launched in August 1994. To date we have performed 22 intestinal transplants, in 9 adults and 13 children. These transplants included 4 isolated intestinal, 11 combined liver-intestinal and 7 multivisceral transplants. Overall patient and graft survival rates were 55% and 50%, respectively. During the past 2 years several studies involving immunosuppressive agents were carried out: 1)Mycophenolate Mofetil (MMF) was used as induction therapy and as rescue therapy in patients with steroid-resistant rejection. Tacrolimus toxicity, and chronic rejection; 2) Neoral was compared with Tacrolimus in patients with Hepatitis C; and 3) MMF was added as triple therapy for the intestinal transplants. We used alpha interferon-2b (alpha-IFN) in hepatitis C positive patients in the early posttransplant period and found that it appears to be a safe drug. There was no increase in rejection in patients receiving alpha-IFN, and patient and graft survival were the same as in our overall patient population. A combination a-IFN with Ribavirin will be undertaken in the near future. The use of Lamivudine in hepatitis B patients was shown to be effective in preventing and treating recurrence of hepatitis B posttransplant. Unmodified donor bone marrow cells (DBMC) were isolated from the vertebral bodies of the same cadaveric liver donors. Donor bone marrow dose, number of cells and/or number (or timing) of infusions were investigated to determine which variables affected the ability of DBMC to engraft in the liver recipient. The long-term benefit of DBMC needs further follow-up. Although, our patient and graft survival for liver transplant recipients is comparable to other large centers nationally and internationally, we still have some challenges to overcome. These include: 1) control and prevention of recurrent HCV, 2) improved treatment for hepatocellular cancer pre- and posttransplant, and 3) treatment and prevention of chronic rejection. Intestinal transplantation remains an even greater challenge. Diagnostic tests to determine intestinal function need further development and although MMF has shown some promise in this field, newer immunosuppressive medications need to be investigated to prevent rejection and avoid over immunosuppression.

Adult↗

PubMed1994

Hepatitis C in liver transplantation: preliminary study of prognostic factors.

At the University of Miami liver transplantation for chronic liver disease in HCV-positive patients has shown good results, with a 92% patients survival rate (follow up 8 to 57 months, median 21). None the less, we found that a large number of patients are expected to develop serious histological graft damage and may need retransplantation, which may place a further strain on the already scarce donor resources. We have conducted a preliminary investigation on the importance of parameters which may correlate with the prognosis of HCV grafts. We found no impact of HLA match or typing. An interesting hypothesis, which deserves further investigation, is that some HCV strains could be more virulent than others and play a role as an independent risk factor. We have identified six strains among our patients and the BK serotype shows a trend to be associated with a worse outcome. We have found that patients developing and maintaining higher liver enzyme levels (ALT and GGT) after transplant and those with higher levels of viremia may be at risk to develop serious damage to their grafts.

Adolescent↗

PubMedDate not supplied

The Miami experience with almost 100 multivisceral transplants.

We report our experience with 98 patients who received primary multivisceral transplantations. Three eras can be distinguished based on the evolution of technique, immunosuppression, and monitoring: August 1994 to December 1997 (first era); January 1998 to December 2000 (second era); and January 2001 to present (third era). Sixteen patients were transplanted during the first era, 18 during the second era, and 64 during the third era. Fifty-three patients are alive with a median follow-up of 37.5 months (range: 1 to 116 months). The leading cause of mortality was infection (n = 17), followed by rejection (n = 6). Seven patients required retransplantation and five of them subsequently died. The estimated 3-year survival was 25% +/- 11% for era 1; 44% +/- 12% for era 2; and 58% +/- 7% for era 3. Additionally, 45.3% (29/64) of patients in the third era never developed rejection versus 23.5% (8/34) of patients in the first two eras combined. The percentage of patients who developed a moderate or severe rejection was significantly less in the third era compared with the first two eras combined, 31.6% (20/64) versus 67.6% (23/34). A comparison of the hazard rate of developing severe rejection showed a protective effect of the multivisceral graft (P = .0001). In conclusion, multivisceral transplantation is indicated for patients with short bowel syndrome and extended abdominal catastrophies. Evolution in surgical techniques, immunosuppression, and monitoring have improved patient survival, which is now similar to that of other complex solid organ transplants.

Cause of Death↗

PubMedDate not supplied

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

INTRODUCTION: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode. METHODS: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period. Serum citrulline measurements were available immediately prior to the occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For the 12 episodes of mild rejection, the mean serum citrulline level +/- SE (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4 micromol/L during the rejection-free periods. A paired t test of the mean differences was not significant (P = 17). For the 25 episodes of moderate or severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A paired t test of the mean difference was statistically significant (P = .002). CONCLUSIONS: Although further study of citrulline as a marker for the early detection of acute rejection episodes is needed, our hope is that its use will help to prevent some of these early episodes from evolving into full-blown moderate or severe grades of rejection.

Acute Disease↗

PubMedDate not supplied

International grading scheme for acute rejection in small bowel transplantation: implementation and experience at the University of Miami.

In 2003, an international collection of pathologists and clinicians proposed a unified grading system for acute cellular rejection in endoscopically derived small intestine allograft biopsies. This grading system was implemented at the University of Miami over the past 2 years and the results are presented herein. A total of 1136 small bowel allograft biopsies with sufficient tissue for analysis were obtained from 123 hospitalized, clinic, and referral patients. The overall most common diagnosis assessing all time periods was grade IND (40%), and grade 1 rejection or greater was present in 19% percent of biopsies. A suspected vascular component to the acute rejection as identified by specific mucosal vascular changes was present in 6% of cases. Clinical decision making was very consistent with different grades. Our experience has confirmed that this new grading system is reliable and identifies clinical subsets of patients that can receive different therapy. We recommend that this international grading system be implemented for acute cellular rejection in bowel allografts as a means to standardize pathological assessment of alloimmune-induced graft injury, which will allow comparisons between different centers and clinical trials.

Florida↗

PubMedDate not supplied

CD55 and CD59 deficiency in transplant patient populations: possible association with paroxysmal nocturnal hemoglobinuria-like symptoms in Campath-treated patients.

Campath-1H therapy is directed to CD52, a small mw protein that has a glycosylphosphatidylinositol (GPI) anchor, which has a conventional structure similar to other GPI anchors such as CD55 and CD59. Paroxysmal nocturnal hemoglobinuria (PNH) results when cells have a somatic defect in the synthesis of GPI anchors and lack CD55 and CD59, as well as CD52. Several patients treated with Campath developed PNH-like symptoms with hemolysis and thrombosis. These patients were followed after therapy by measurement of peripheral CD55 and CD59 levels and showed an increased number of cells deficient in the expression of these molecules. Thereafter we instituted a screening program for the presence of CD55/59 levels in all pretransplant patients. Our results show that 17.3% of all pretransplant samples contained abnormal (9.7% of samples) or slightly abnormal (7.6% of samples) levels of granulocytes deficient in CD55 or CD59. This high prevalence of CD55/59 deficiency in Campath-treated patients with PNH-like symptoms suggests that a lack of these molecules (including CD52) could predispose to a complication of this immunosuppressive therapy.

Alemtuzumab↗

PubMedDate not supplied

Mucosal fibrosis in intestinal transplant biopsies correlates positively with the development of chronic rejection.

Endoscopic biopsies of intestinal allografts are limited to the superficial layers of the bowel. We investigated whether the presence of mucosal fibrosis in graft biopsies was indicative of chronic allograft rejection. We examined graft biopsies of 182 intestinal transplant recipients for the presence of mucosal fibrosis. Kaplan-Meier analysis showed that within 5 years posttransplantation 33% of intestinal transplant patients had graft biopsies positive for mucosal fibrosis. Although the presence of mucosal fibrosis did not affect patient or graft survival, patients with this lesion were at higher risk of developing chronic allograft enteropathy.

Adult↗

PubMedDate not supplied

Etiology and management of alimentary tract ulcers in pediatric intestinal transplantation patients.

Patients who undergo intestinal transplantation encounter several complications in the posttransplant period, one of them being ulcer formation in the alimentary tract. During postoperative endoscopic monitoring of 112 pediatric intestinal transplantation patients at our institution, we identified chronic ulcer formation in 11 patients. There were no common or defining demographic or clinical variables that were found in the patients with ulcers. The ulcers could be located within the allograft or in native tissue. Biopsies were obtained from the ulcer edge and the intervening mucosa as well as an evaluation of possible infectious agents. The most common changes in the ulcers were compatible with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (PTLD; seven cases), acute rejection (six cases), and less commonly, infectious causes (one case). These changes could occur concomitantly and retrospective analysis after therapy showed that the ulcers could have multiple etiologies. Directed biopsies of ulcer edges often displayed morphological changes compatible with acute rejection of the graft, although some biopsies of the intervening mucosa did not show similar changes. Some patients treated based on the changes within the intervening mucosa responded well and led to resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection are the most common causes of chronic ulcer formation and that biopsy samples should be collected simultaneously from both the ulcer edge and intervening mucosa since pathological changes can vary depending on the underlying cause(s). Infectious agents were rarely present but could be seen superimposed with the underlying cause.

Biopsy↗

PubMedDate not supplied

Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients.

BACKGROUND: Alemtuzumab (Campath-1H [C1H]) is a humanized monoclonal antibody directed against the CD 52 antigen that is present on the surface of T cells, B cells, natural killer cells and monocytes. We studied its application in intestinal transplantation. METHODS: This is a retrospective review of adult patients who underwent intestinal transplantation between December 1994 and May 2005. Group 1: non-C1H group (n = 39); group 2: C1H group (n = 37). C1H was administered as an induction immunosuppression in four doses (0.3 mg/kg), or in two doses (30 mg/kg). Tacrolimus levels were maintained at low level (5-10 ng/dL). No maintenance steroids were given. RESULTS: One-year survival of group 1 and group 2 patients were 57% and 70%, respectively. This difference is not statistically significant. Of 37 patients in group 2, 21 are alive. The incidence of rejection was lower in group 2 (P < .005). Average current tacrolimus level is 6.97 +/- 3.98 ng/dL. Seventeen patients (81%) are steroid free, and 15 (71%) are maintained solely on tacrolimus. There was no graft versus host disease in group 2. CONCLUSIONS: Our preliminary data suggest that C1H can provide effective immunosuppression for intestinal transplantation. Incidence of rejection was less with this regimen using low maintenance tacrolimus and minimal steroids.

Adult↗

PubMedDate not supplied