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Biomedical subjects

D Weppler

Publications and source records attributed to D Weppler.

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↗
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

Immunoenzymatic and morphological detection of epithelial cell apoptotic stages in gastrointestinal allografts from multivisceral transplant patients.

Acute allograft rejection (AR) is a major contributor to morbidity and mortality among patients who undergo multivisceral transplantation. Critical to the assessment of AR is detection of apoptosis in the glandular epithelium of the gastrointestinal allograft. We utilized the TUNEL stain (TdT-mediated biotin 16-dUTP nick-end labeling) to test whether this method improved detection of apoptosis compared to standard slide evaluation. TUNEL and H&E stains were performed on paraffin-embedded tissue sections to estimate the number of apoptotic bodies per 10 high power fields, as determined by independent pathologists in blinded fashion. Both methodologies showed similar numbers and distributions of apoptotic foci present among the epithelial cells. There was a correlation between the number of apoptosis and the grade of rejection (P <.001). This is the first use of the TUNEL stain in gastrointestinal allograft biopsies to our knowledge. The similarity in pattern and sensitivity of TUNEL with standard morphology confirms that biopsy assessment with routine H&E staining allows an accurate appraisal of epithelial cell apoptosis. Therefore, current staining protocols for endoscopically derived mucosal biopsies of gastrointestinal allografts are sufficiently accurate to enumerate the critical feature of epithelial apoptosis as a determinant of the grade of acute rejection.

Apoptosis↗
PubMed2004

Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation.

Campath-1H, an anti-CD52 antibody, is being used at our institution as immunosuppression in multivisceral and intestinal transplantation. We reviewed the pathologic findings of 1696 small bowel allograft biopsies obtained in the first 250 days posttransplant from 78 patients who underwent isolated intestinal or multivisceral transplantation and received induction immunosuppression with Campath (n = 30) or Zenapax (n = 57). We found an overall reduced incidence of acute cellular rejection (ACR) in patients receiving Campath (19.1%) compared with those on Zenapax (32.8%). The majority of Campath patients showed no rejection or was indeterminate for rejection over the period of measurement. The frequencies of mild and moderate ACR were approximately twice and three times more common, respectively, in Zenapax-treated patients. The mean grade of ACR in Campath patients compared with Zenapax patients was significantly lower (P <.01) during the first 6 weeks posttransplant. Thereafter, the grade of rejection in both patient groups showed fluctuation, with Zenapax patients sometimes having lower values (eg, at 2 to 4 months) than Campath patients. Patient and graft survival was not significantly different between the two groups. These data suggest that the incidence of ACR is significantly reduced with Campath during the first 2 months posttransplant, when compared with Zenapax. However, the incidence and intensity of ACR following this initial time period shows vacillation with both types of immunosuppression.

Alemtuzumab↗
PubMed2003

Sclerosing mesenteritis in small bowel transplantation: possible manifestation of acute vascular rejection.

BACKGROUND: Acute rejection of human small bowel allografts is characterized by clinical symptoms combined with characteristic morphologic alterations. The typical geographic distribution of acute rejection in the bowel is involvement of the intestinal parenchyma, which can be transmural, particularly when the rejection is more severe. However, little is known concerning the potential for donor-derived soft tissue adjacent to the bowel to become involved by the host alloimmune response. METHODS: We describe a male patient who, several weeks after combined small bowel and liver transplantation, demonstrated sclerosing mesenteritis with vasculitis and acute rejection of the bowel. RESULTS: The vascular lesions in the mesentery demonstrated increased IgG deposition and the patient developed an alloantibody to the donor. CONCLUSIONS: The changes described herein may represent a novel presentation of acute vascular rejection.

Acute Disease↗
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

Bacterial infections after intestine and multivisceral transplantation.

BACKGROUND: The frequency of bacterial infections (BI) in intestinal transplant (IT) patients is high with sepsis being the leading cause of death after this procedure. We herein report our experience with major BI to ascertain the incidence, microbiological and clinical factors, risk factors and outcome. MATERIALS AND METHODS: 124 patients (72 children and 52 adults) received 135 grafts: namely, 39 isolated intestine, 33 liver-intestine and 63 multivisceral. Only major BI were considered, namely, those associated with serious morbidity/mortality requiring specific therapy. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: 92.7% patients showed BI. There were 327 episodes, representing 2.6 episodes/patient (2.8/patients with infection): 193 episodes of bacteremia (1.7/patient with BI) including 29.5% due to catheter related sepsis, 16.5% from abdominal source, 5.7% from respiratory origin and 4.1% from the wound. The organ locations includes 46 respiratory infections, 33 intraabdominal abscesses or infected fluid collections, 8 diffuse peritonitis, 34 wound infections and other miscellaneous sites: empyema, soft tissue infections, cholangitis em leader etc. Median time of infection was nine days after surgery (mean 22+/-3 days), with 67.7% patients having at least one BI before the end of the first month. Infection was present in 76.2% of the 63 deceased patients. An infectious episode during month 1, a clinically manifest abdominal infection and a positive intraabdominal culture had negative impacts on patient survival. CONCLUSIONS: BI are common and early complications after IT. The high rate of bacteremia, line sepsis and abdominal and respiratory infections reflect the recipient's condition, with chronic deterioration superimposed with the effects of prolonged abdominal visceral surgery.

Adult↗
PubMed2001

Intestinal transplantation for the treatment of desmoid tumors associated with familial adenomatous polyposis.

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP) are locally invasive. Often occurring in the mesentery of the intestine, they sometimes recur after resection. Complications can include intestinal failure and dependence on parenteral nutrition. We describe 9 patients who underwent intestinal transplantation for the treatment of desmoid tumors associated with FAP. METHODS: Records of patients undergoing intestinal transplantation for desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type of graft, procedure date, tumor site, desmoid complications, medications, extracolonic manifestations, status at follow-up, and length of survival. RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One graft lost to severe rejection was replaced with a second intestinal graft. Eleven to 53 months after transplantation, 7 patients were alive, well, independent of parenteral treatment, and leading apparently normal lifestyles. CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral transplantation may help rescue otherwise untreatable patients with complicated desmoid tumors.

Adenomatous Polyposis Coli↗