C. Zanfi

Liver transplantations with donors aged 60 years and above: the low liver damage strategy

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999–2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged ≥ 60 years and managed with the low liver‐damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D ≥ 60‐LLDS). Group D ≥ 60‐LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60‐no‐LLDS and 89 donors aged ≥60 years, group D ≥ 60‐no‐LLDS). In the donors proposed from the age group of ≥60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end‐stage liver disease score) were comparable among groups, but group D ≥ 60‐LLDS had a lower mean ischemia time: 415 ± 106 min vs. 465 ± 111 (D < 60‐no‐LLDS), P < 0.05 and vs. 476 ± 94 (D ≥ 60‐no‐LLDS), P < 0.05. After a median follow‐up of 3 years, the 1‐ and 3‐year graft survival rates of group D ≥ 60‐LLDS (84% and 76%) were comparable with group D < 60‐no‐LLDS (89% and 76%) and were significantly higher than group D ≥ 60‐no‐LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.

Assessment of Quality of Life on Home Parenteral Nutrition and After Intestinal Transplantation Using Treatment‐Specific Questionnaires

In order to investigate the quality of life on home parenteral nutrition and after intestinal transplantation using comparable questionnaires, the treatment‐specific quality of life questionnaire for adult patients on home parenteral nutrition was adapted for intestinal transplant recipients. Both instruments were composed of 8 functional scales, 9 symptom scales, 3 global health status/quality of life scales and 2 single items. A preliminary cross‐sectional study enrolling all the patients currently cared at the same hospital was carried out. Exclusion criteria were age ≥ 60 years and hospitalization at time of assessment. Thirty‐three home parenteral nutrition patients (100% answered) and 22 intestinal transplant recipients (82% answered) were enrolled. Intestinal transplant recipients showed a better score in following scales: ability to holiday/travel (p < 0.001), fatigue (p = 0.022), gastrointestinal symptoms (p < 0.001), stoma management/bowel movements (p = 0.001) and global health status/quality of life (p = 0.012). A better score for ability to eat/drink (p = 0.070) and a worse score for sleep pattern (p = 0.100) after intestinal transplantation were also observed. The results of this preliminary study with specific instruments were consistent with the main expected improvement of the quality of life related to intestinal transplantation. Further studies in larger patient cohorts are required to confirm these data.

Risk of Kaposi Sarcoma after Solid-Organ Transplantation: Multicenter Study in 4767 Recipients in Italy, 1970–2006

Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10(5) PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.

Incidence and management of abdominal closure-related complications in adult intestinal transplantation.

Background. We sought to determine the best strategy to overcome difficult abdominal wall closures in intestinal transplantation (ITx). Methods. Among 38 adult recipients of 39 ITxs from deceased donors, the median number of previous laparotomies was 2.0 per patient, with a median donor-to-recipient body weight ratio of 1.1. Eight patients (21%) had full residual intestinal length before transplant. Abdominal wall closure after transplant was considered difficult in 15 (39.5%) patients (group A). To overcome size mismatching, we performed two graft reductions, five skin-only closures, one two-step abdominal wall closure, four prosthetic mesh closures, and three abdominal wall transplants. In the remaining 23 (60.5%) patients, a regular abdominal closure was performed (group B). Results. Twelve patients (32%) experienced complications related to abdominal wall closure, 10 (67%) in group A and 2 (8.7%) in group B (P<0.0001). Abdominal closure-related mortality was 6.7% (1/15) and 4.3% (1/23), respectively (P=1.0). In group A, there were six incisional hernias (one of them after abdominal wall transplant), although all four patients with mesh experienced mesh infection. Two of them developed intestinal fistulae, leading to patient death in one case. In group B, one patient with unfavorable donor/recipient size matching had fatal vascular thrombosis of a multivisceral graft caused by compression after abdominal closure. Conclusions. A careful evaluation of abdominal cavity is necessary in candidates for ITx. In our experience, closure with mesh should be avoided because of the high rate of complications. Abdominal wall transplantation is a feasible option when a difficult abdominal wall closure is expected.

Twenty-five consecutive isolated intestinal transplants in adult patients: a five-yr clinical experience

Abstract: Patients and Methods:  Between December 2000 and December 2005, 25 isolated intestinal transplants from cadaveric donors have been performed for short gut syndrome (short bowel syndrome, 52%), chronic intestinal pseudo‐obstruction (24%), Gardner syndrome (16%), radiation enteritis (4%) and massive intestinal angiomatosis (4%). Indications for transplantation were: loss of venous access, recurrent sepsis due to central line infection, major electrolyte and fluid imbalance. Liver dysfunction was present in 13 cases. All patients were adult; median age was 36.3 yr and mean weight at transplantation 61.6 kg. All recipients were on life‐threatening parenteral nutrition for a mean time of 23.7 months. Mean donor/recipient body weight ratio was 1.08. Rejection monitoring was accomplished by graft ileoendoscopies and intestinal biopsies through the temporary ileostomy. Our immunosuppressive regimen was based on induction therapy with three different protocols: daclizumab for induction, tacrolimus and steroids as maintenance therapy; alemtuzumab for induction and low‐dose tacrolimus as maintenance; thymoglobulinTM for induction and maintenance based on low‐dose tacrolimus. Closure of the abdomen at the end of transplantation represented a technical problem with several options performed: graft reduction, only skin closure, prothesic meshes, abdominal closure in two steps, cutaneous flaps and abdominal wall transplant in one case.

Isolated intestinal transplant for chronic intestinal pseudo-obstruction in adults: long-term outcome.

BACKGROUND Chronic intestinal pseudo-obstruction (CIPO) has been treated in adults by total parenteral nutrition (TPN) or, if complications arise, by multivisceral transplantation because the stomach is often involved. Eleven adults with CIPO were transplanted by intestinal graft in our center from 2000 to 2011. METHODS Nine patients underwent isolated intestinal transplant and 2 patients had multivisceral transplant. Immunosuppression was represented by FK and steroids plus induction with alemtuzumab, daclizumab, or thymoglobulin. Average age at transplant was 33.5 years. We reported 1 graftectomy, followed by retransplantation. RESULTS Seven patients are currently alive with working small bowel; cause of death was infection in the 4 remaining cases. In 9 isolated intestinal transplants, we performed different digestive reconstructions to allow gastric emptying. In 2 cases we were forced, after transplant, to perform ileostomy to improve intestinal motility. Graft and patient survival after 5 years are 60% and 70%, respectively, while after 10 years, 45% and 56%, respectively. CONCLUSIONS Adults with CIPO and irreversible TPN complications benefit from isolated intestinal transplant with different surgical techniques to empty the native stomach: this strategy achieves good gastric emptying, with effective establishment of oral feeding and graft and patient survivals comparable to isolated intestinal transplant for short bowel syndrome.

Early and Late Virological Monitoring of Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 Infections in Small Bowel/Multivisceral Transplant Recipients

BACKGROUND Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations (SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients. STUDY PURPOSE The purposes of this study were to analyze the clinical relevance of CMV, EBV, and HHV-6 infections after small bowel transplantation and to establish whether routine monitoring for HHV-6 infection should be recommended for the prevention of severe complications in this population. METHODS Ten adult patients were monitored based on CMV, EBV, and HHV6 DNA quantifications in blood and biopsy tissue samples. Three patients were monitored for at least 5 months (early period) and 7 patients were monitored for 1 to 5 years after transplantation (late period). RESULTS In the early period, despite prophylaxis all 3 patients developed symptomatic CMV infections: 1 fever/diarrhea, 1 enteritis and rejection, as well as 1 fever and pneumonia. Only 1 patient developed EBV and HHV-6 infections. The average time of onset of CMV infection was 3 months after transplantation and only 24 days for HHV6 infection. In the late period, of the 7 SB/MVT recipients only 1 developed an EBV infection at 2 years after transplantation. No CMV or HHV-6 infections were identified in any patient. CONCLUSIONS CMV infection is a major cause of organ disease and rejection in the early period after transplantation. EBV infection in adult recipients must be considered also in the late period, particularly in association with severe immunosuppression. Because HHV-6 infection occurs earlier than CMV/EBV, it may serve as an indicator for more intense virological surveillance.

Anatomic Variations of Intrahepatic Bile Ducts in a European Series and Meta-analysis of the Literature

BackgroundAccurate knowledge of biliary anatomy and its variants is essential to ensure successful hepatic surgery; however, data from European countries are lacking.MethodsTwo hundred cholangiograms obtained from patients submitted to whole liver transplantation were reviewed; donors’ characteristics were related to the prevalence of typical biliary anatomy and its variants. A comprehensive literature search was performed with MEDLINE and EMBASE from 1980 to 2010 to investigate whether geographical origin could be related to biliary abnormalities.ResultsTypical biliary anatomy was observed in 64.5% of cases, but female donors more frequently presented an anatomic variation; typical anatomy was present in 55.0% of females and in 74.0% of males (P = 0.005). Twenty-two reports were identified by the literature search with a total of 7,559 cases, including the present series; heterogeneity was low (Q = 14.60; I2 < 5.0%) after exclusion of three outlier reports. Prevalence of typical biliary anatomy was similar in Europeans and Americans (∼60%); a slightly higher prevalence was observed in Asiatics (∼65%).ConclusionsAnatomic variants seem to be more frequent in females, probably as a consequence of different embryologic development. Available data suggest that typical biliary anatomy can be more frequent in Asiatics, but an accurate means of classification is essential to making comparison realistic.

Renal function in patients on long-term home parenteral nutrition and in intestinal transplant recipients

OBJECTIVE A decrease of renal function was described in patients on long-term home parenteral nutrition (HPN) for benign intestinal failure. The risk for chronic renal failure (CRF) due to frequent episodes of dehydration despite optimal HPN, is an indication for intestinal transplantation (ITx). ITx is the solid organ transplant at highest risk for developing CRF. The aim of this study was to compare the prevalence and the probability of CRF occurring in adults on HPN and after ITx. METHODS A cross-sectional and retrospective follow-up study was carried out in 2011. Renal function was evaluated at cross-sectional and at time of starting HPN or ITx, by serum creatinine concentration (mg/dL) and estimated glomerular filtration rate (eGFR), according to the Modification of Diet in Renal Disease equation (mL·min·1.73 m2). CRF was defined as eGFR <60. Duration of follow up was from time of starting treatment to time of cross-sectional. RESULTS We enrolled 33 patients on HPN and 22 who had undergone ITx. The frequency of CRF was 6% in the HPN group and 9% in the ITx group (P = 0.67) at start of treatment, and 21% and 54%, respectively (P = 0.01) at the time of the cross-sectional evaluation. During the follow-up, the annual decline of eGFR was 2.8% and 14.5%, respectively (P = 0.02). The 5-y probability of maintaining an eGFR ≥60 was 84% in the HPN group and 44% in the ITx group (P < 0.001). CONCLUSIONS The decrease of renal function and the risk for developing CRF are greater after ITx than during HPN. The risk for CRF on HPN, as a criterion for ITx, should be revised.

Bacterial Translocation in Adult Small Bowel Transplantation

The application of intestinal transplantation is limited by the high rate of infectious complications that can occur; the migration of enteric microorganisms to extraintestinal sites (bacterial translocation) has been suggested to be responsible for this event. We reviewed 95 intestinal biopsies performed on 28 transplanted patients to identify histologic features predictive of isolation of enteric microorganisms in extraintestinal sites within the first month after transplantation. At least 1 isolation of enteric microorganisms in the peritoneal cavity and/or in blood samples was obtained in 13 patients (46.4%); this event led to higher 1-year mortality (38.5% vs. 6.7%; P = .041). Of the 95 biopsies, 38 were followed by positive cultures (40.0%), showing higher degrees of mucosal vascular alterations (Ruiz grade) and ischemia/reperfusion injuries (Park/Chiu grade) compared with the negative cases (P < .05). We also observed an higher prevalence of positive cultures in relation to acute cellular rejection episodes (P = .091). Neither clinical or surgical factors nor immunosuppressive therapy were observed to be significantly related to positive cultures. Histologic alterations of the small bowel allograft are related to isolation of enteric microorganisms in extraintestinal sites. The degree of these histologic features can identify patients at high risk of potentially life-threatening infectious complications and death.