David Levi

Transplantation of the abdominal wall

BACKGROUND Closure of the abdomen in patients undergoing intestinal transplantation can be extremely difficult, if not impossible. We describe our initial experience with abdominal wall allotransplantation to facilitate abdominal closure. METHODS We undertook nine cadaveric abdominal wall composite allograft transplants in eight patients. The grafts blood supply was based on the inferior epigastric vessels left in continuity with the donor femoral and iliac vessels. Skin biopsies were undertaken randomly and when rejection was suspected. Vessel patency was monitored by doppler ultrasound. FINDINGS Six patients have survived, five of whom have intact, viable abdominal wall grafts. Two patients have had a clinically mild episode of acute rejection of the skin of the abdominal wall that resolved with corticosteroid therapy. No clinically apparent graft-versus-host disease has been noted. INTERPRETATION Transplantation of an abdominal wall composite allograft can facilitate reconstruction and closure of the abdominal compartment in intestinal transplant recipients with complex abdominal wall defects.

100 Multivisceral Transplants at a Single Center

Objective:The objective of this study was to summarize the evolution of multivisceral transplantation over a decade of experience and evaluate its current status. Summary Background Data:Multivisceral transplantation can be valuable for the treatment of patients with massive abdominal catastrophes. Its major limitations have been technical and rejection of the intestinal graft. Methods:This study consisted of an outcome analysis of 98 consecutive patients who received multivisceral transplantation at our institution. This represents the largest single center experience to date. Results:The most common diseases in our population before transplant were intestinal gastroschisis and intestinal dysmotility syndromes in children, and mesenteric thrombosis and trauma in adults. Kaplan Meier estimated patient and graft survivals for all cases were 65% and 63% at 1 year, 49% and 47% at 3 years, and 49% and 47% at 5 years. Factors that adversely influenced patient survival included transplant before 1998 (P = 0.01), being hospitalized at the time of transplant (P = 0.05), and being a child who received Campath-1H induction (P = 0.03). Among 37 patients who had none of these 3 factors (15 adults and 22 children), estimated 1- and 3-year survivals were 89% and 71%, respectively. Patients transplanted since 2001 had significantly less moderate and severe rejections (31.6% vs 67.6%, P = 0.0005) with almost half of these patients never developing rejection. Conclusions:Multivisceral transplantation is now an effective treatment of patients with complex abdominal pathology. The incidences of serious acute rejection and patient survival have improved in the most recent experience. Our results show that the multivisceral graft seems to facilitate engraftment of transplanted organs and raises the possibility that there is a degree of immunologic protection afforded by this procedure.

Ninety-five cases of intestinal transplantation at the University of Miami.

Intestinal failure requiring total parenteral nutrition (TPN) is associated with significant morbidity and mortality. Intestinal transplantation can be a lifesaving option for patients with intestinal failure who develop serious TPN-related complications. The aim of this study was to evaluate survival, surgical technique, and patient care in patients treated with intestinal transplantation. We reviewed data collected from 95 consecutive intestinal transplants performed between December 1994 and November 2000 at the University of Miami. Fifty-four of the patients undergoing intestinal transplantation were children and 41 were adults. The series includes 49 male and 46 female patients. The causes of intestinal failure included mesenteric venous thrombosis (n = 12), necrotizing enterocolitis (n = 11), gastroschisis (n = 11), midgut volvulus (n = 9), desmoid tumor (n = 8), intestinal atresia (n = 6), trauma (n = 5), Hirschsprung’s disease (n = 5), Crohn’s disease (n = 5), intestinal pseudoobstruction (n = 4), and others (n = 19). The procedures performed included 27 isolated intestine transplants, 28 combined liver and intestine transplants, and 40 multivisceral transplants. Since 1998, we have been using daclizumab (Zenepax) for induction of immunosuppression and zoom videoendoscopy for graft surveillance. We began to use intense cytomegalovirus prophylaxis and systemic drainage of the portal vein. The 1-year patient survival rates for isolated intestinal, liver and intestinal, and multivisceral transplantations were 75%, 40%, and 48%, respectively. Since 1998, the 1-year patient and graft survival rates for isolated intestinal transplants have been 84% and 72%, respectively. The causes of death were as follows: sepsis after rejection (n = 14), respiratory failure (n = 8), sepsis (n = 6), multiple organ failure (n = 4), arterial graft infection (n = 3), aspergillosis (n = 2), post-transplantation lymphoproliferative disease (n = 2), intracranial hemorrhage (n = 2), and fungemia, chronic rejection, graft vs. host disease, necrotizing enterocolitis, pancreatitis, pulmonary embolism, and viral encephalitis (n = 1 case of each). Intestinal transplantation can be a lifesaving alternative for patients with intestinal failure. The prognosis after intestinal transplantation is better when it is performed before the onset of liver failure. Rejection monitoring with zoom videoendoscopy and new immunosuppressive therapy with sirolimus, daclizumab, and campath-1H have contributed to the improvement in patient survival.

Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation.

Background. The administration of alemtuzumab (Campath-1H [C1H]; Berlex Laboratories, Montville, NJ) at transplantation prevents a vigorous immune response and is believed to allow a gradual engagement of the host immune system. We report our preliminary experience with C1H and tacrolimus (Tac) immunosuppression in adult liver transplantation. Methods. We administered C1H and low-dose Tac to 40 adult recipients of cadaveric liver allografts between December 2001 and April 2003. A control group who met the same eligibility criteria consisted of 50 liver transplant recipients treated with our standard Tac and steroids protocol. Results. Baseline characteristics and patient and graft survival were similar (P >0.15). The incidence of acute rejection was significantly lower during the first 2 months posttransplantation (P =0.002) and slightly lower overall in the study group versus the control group at 12 months (46% vs. 55%, P =0.12, log-rank test). Median time to rejection among those experiencing rejection was significantly longer in the study group versus control group (2.76 vs. 0.34 months, P =0.0007). The mean Tac dose, 12-hr trough level, and percentage of patients receiving maintenance steroids were significantly lower in the group receiving C1H and Tac (P <0.0001 during the first 3 months, P <0.05 thereafter), as were the mean creatinine levels (P <0.05) and incidence of nephrotoxicity (P =0.004, conversion from Tac to other agents). Finally, in the group receiving C1H/Tac, patients with an average Tac trough level less than 6.5 ng/mL during the first 2 months post-transplantation demonstrated a significantly higher rejection rate beyond that time (P =0.02). Conclusion. C1H and low-dose Tac seems to be at least as effective as our standard Tac and steroids regimen in preventing acute rejection in adult liver allotransplantation with less renal toxicity and less use of maintenance steroids.

Intestinal and Multivisceral Transplantation in Children

Objective:To describe a single-center experience of pediatric intestinal transplantation (Itx) and to provide an overview of the children who underwent this procedure along with their outcomes. Summary Background Data:Pediatric Itx presents multiple challenges because of the very young ages at which patients require transplantation and their higher susceptibility to infectious complications. Methods:We have performed 141 Itx in 123 children with a median age of 1.37 years. Primary grafts included isolated intestine (n = 28), liver and intestine (n = 27), multivisceral (n = 61), and multivisceral without the liver (n = 7). Two protocol modifications were introduced in 1998: daclizumab induction and frequent rejection surveillance. In 2001, indications for multivisceral transplantation were expanded, and induction with Campath-1H was introduced. Results:Actuarial patient survival at 1 and 3 years for group 1 (January 1994 to December 1997, n = 25), group 2 (January 1998 to March 2001, n = 29), group 3a (April 2001 to present, daclizumab, n = 51), and group 3b (April 2001 to present, Campath-1H, n = 18) was 44%/32%, 52%/38%, 83%/60%, and 44%/44%, respectively (P = 0.0003 in favor of group 3a). Severe rejection implied a dismal prognosis (65% mortality at 6 months). Observed incidence of severe rejection in groups 1, 2, 3a, and 3b was 32%, 24%, 14%, and 11%, respectively. In multivariable analysis, use of a multivisceral (with or without liver) transplant (P = 0.002), induction with daclizumab (P = 0.005), patient at home prior to transplant (P = 0.007), and age at transplant ≥1 year (P = 0.02) favorably influenced patient survival. Multivisceral transplant was protective with respect to the mortality rate due to rejection, while an older age at transplant was associated with both a lower incidence rate of developing respiratory infection and lower risk of mortality following the respiratory infection. Survivors are off parenteral nutrition and have demonstrated significant growth catch-up. Conclusions:Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.

Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center

BACKGROUND Cystic lesions of the liver consist of a heterogeneous group of disorders and may present a diagnostic and therapeutic challenge. Large hepatic cysts tend to be symptomatic and can cause complications more often than smaller ones. STUDY DESIGN We performed a retrospective review of adults diagnosed with large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15 years. Polycystic disease and abscesses were not included. RESULTS Seventy-eight patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary cystadenocarcinoma. In four patients, the precise diagnosis could not be ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection (one patient) were rare manifestations. Percutaneous aspiration of 28 simple cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months (mean 4(1/2) months). Forty-eight patients were treated surgically by wide unroofing or resection (laparoscopically in 18), which resulted in low recurrence rates (11% for laparoscopy and 13% for open unroofing). Four of the eight patients with echinococcal cysts were symptomatic. All were treated by open resection after irrigation of the cavity with hypertonic saline. There was no recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe (left:right, 8:0). Seven were multiloculated. All were treated by open resection, with no recurrence, and none had malignant changes. Cystadenocarcinoma was diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy. CONCLUSIONS Large symptomatic simple cysts invariably recur after percutaneous aspiration. Laparoscopic unroofing can be successfully undertaken, with a low recurrence rate. Open resection after irrigation with hypertonic saline is a safe and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have predilection for women and for the left hepatic lobe. Malignant transformation is an uncommon but real risk. Open resection is a safe and effective treatment for hepatobiliary cystadenoma, and is associated with a low recurrence rate.

The Role of Donor Bone Marrow Infusions in Withdrawal of Immunosuppression in Adult Liver Allotransplantation

We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post‐transplantation, with stable graft function. Forty‐five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year.

Laparoscopic cholecystectomy in cirrhotic patients

BACKGROUND Reported mortality for open cholecystectomy in patients with cirrhosis ranges from 10% to 80%. Laparoscopic cholecystectomy has gained acceptance in the general population and has become the procedure of choice for symptomatic cholelithiasis. We reviewed our experience with the use of laparoscopic cholecystectomy in this group. STUDY DESIGN We did a retrospective review of the records of 25 consecutive laparoscopic choleoystectomy procedures performed on cirrhotic patients from May 1992 to July 1996. RESULTS There were no mortalities in our group. All procedures were completed laparoscopically. Mean length of stay was 1.7 days (range, 1 to 8 days). Morbidity consisted of wound hematomas, pneumonia, and ascites for a rate of 32%. Only patients with Childs Class A and Class B cirrhosis were operated on. CONCLUSIONS Laparoscopic cholecystectomy can be performed safely in cirrhotic patients with well compensated liver function.

Alemtuzumab (Campath-1H) combined with tacrolimus in intestinal and multivisceral transplantation

Background. We combined alemtuzumab (Campath-1H, Berlex Laboratories, Montville, NJ) and tacrolimus (Tac) immunosuppression for intestinal and multivisceral transplantation. Materials and Methods. A total of 21 adult patients received 24 grafts: 14 intestinal, nine multivisceral, and one liver-intestinal graft. Alemtuzumab was administered perioperatively in four doses with low-dose Tac (levels 10–15 ng/dL) and no maintenance steroids. Tac was substituted with sirolimus in case of Tac-related complications. Suspected or mild rejections were treated with steroids. Moderate rejections were treated with steroids or OKT3. Severe rejections were treated with OKT3. Results. Of the 16 patients that were followed up for an average of 9 months, 12 are alive with functioning grafts. Two patients experienced severe rejection, three experienced moderate rejection episodes, and seven experienced mild acute rejection episodes. Four patients never developed acute rejection. Infectious complications included a cytomegalovirus enteritis and four fungal infections (related to central venous access). Conclusions. The combination of alemtuzumab and Tac therapy without steroid use seems to efficiently prevent acute rejection in a significant number of patients without causing frequent opportunistic infections.

Is surgical resection superior to transplantation in the treatment of hepatocellular carcinoma

Objective:To compare outcomes for patients with hepatocellular carcinoma (HCC) treated with either liver resection or transplantation. Methods:A retrospective, single-institution analysis of 413 HCC patients from 1999 to 2009. Results:A total of 413 patients with HCC underwent surgical resection (n = 106) and transplantation (n = 270) or were listed without receiving transplantation (n = 37). Excluding transplanted patients with incidental tumors (n = 50), 257 patients with suspected HCC were listed with the intent to transplant (ITT). The median diameter of the largest tumor by radiography was 6.0 cm in resected, 3.0 cm in transplanted, and 3.4 cm in the listed-but-not-transplanted patients. Median time to transplant was 48 days. Recurrence rates were 19.8% for resection and 12.1% for all ITT patients. Overall, patient survival for resection versus ITT patients was similar (5-year survival of 53.0% vs 52.0%, not significant). However, for HCC patients with model end-stage liver disease (MELD) scores less than 10 and who radiologically met Milan or UCSF (University of California, San Francisco) criteria, 1-year and 5-year survival rates were significantly improved in resected patients. For patients with MELD score less than 10 and who met Milan criteria, 1-year and 5-year survival were 92.0% and 63.0% for resection (n = 26) versus 83.0% and 41.0% for ITT (n = 73, P = 0.036). For those with MELD score less than 10 and met UCSF criteria, 1-year and 5-year survival was 94.0% and 62.0% for resection (n = 33) versus 81.0% and 40.0% for ITT (n = 78, P = 0.027). Conclusions:Among known HCC patients with preserved liver function, resection was associated with superior patient survival versus transplantation. These results suggest that surgical resection should remain the first line therapy for patients with HCC and compensated liver function who are candidates for resection.