A multi-national survey of experience and attitudes towards commencing home parenteral nutrition for patients with advanced cancer.

INTRODUCTION: Advanced cancer (AC) is increasingly an indication for home parenteral nutrition (HPN) but an area with possible variation in practice between geographical locations. The aims of this study are to explore the views and experiences of international multi-disciplinary teams to determine opinions and practices. METHODS: An online questionnaire was developed with members of the Home Artificial Nutrition and Chronic Intestinal Failure interest group of the European Society for Clinical Nutrition and Metabolism (ESPEN) and distributed to colleagues involved in managing patients with AC on HPN. RESULTS: A total of 220 responses were included from 5 continents including 36 countries, with 90% of all responses from Europe. Predicted survival was a key factor influencing the decision to commence HPN for most respondents 152/220 (75%), with the majority of participants reporting that patients should have a predicted survival of ≥3 months if considered for HPN (≥3 months: n = 124, 56% vs. <3 months: n = 47, 21%, p < 0.001). However, most respondents were not confident about predicting overall survival in more than 50% of cases (confident n = 40, 23% vs not confident n = 135, 77%, p < 0.001). Barriers to utilising HPN in AC included colleagues' objections (n = 91, 46%), lack of local expertise (n = 55, 28%) and funding restrictions (n = 34, 17%). CONCLUSIONS: Significant consensus was observed regarding AC as indication for HPN, while areas of variation exist. Survival prognostication is often used as an indication for commencing HPN in people with AC, although the majority of respondents were not confident in prognosticating, suggesting better clinical prognostication tools will be of assistance. Further studies are also required to better understand the obstacles faced by clinical teams to commencing HPN that may explain variations in clinical practice between countries, as well as adressing variation in funding.

Multimodal Surgical Approach for Adult Patients With Chronic Intestinal Pseudo-Obstruction: Clinical and Psychosocial Long-term Outcomes.

BACKGROUND: Clinical and psychosocial outcomes of a multimodal surgical approach for chronic intestinal pseudo-obstruction were analyzed in 24 patients who were followed over a 2- to 12-year period in a single center after surgery or intestinal/multivisceral transplant (CTx). METHODS: The main reasons for surgery were sub-occlusion in surgery and parenteral nutrition-related irreversible complications with chronic intestinal failure in CTx. RESULTS: At the end of follow-up (February 2015), 45.5% of CTx patients were alive: after transplantation, improvement in intestinal function was observed including a tendency toward recovery of oral diet (81.8%) with reduced parenteral nutrition support (36.4%) in the face of significant mortality rates and financial costs (mean, 202.000 euros), frequent hospitalization (mean, 8.8/re-admissions/patient), as well as limited effects on pain or physical wellness. CONCLUSIONS: Through psychological tests, transplant recipients perceived a significant improvement of mental health and emotional state, showing that emotional factors were more affected than were functional/cognitive impairment and social interaction.

Reconnection surgery in adult post-operative short bowel syndrome < 100 cm: is colonic continuity sufficient to achieve enteral autonomy without autologous gastrointestinal reconstruction? Report from a single center and systematic review of literature.

A systematic bibliographic research concerning patients operated on for SBS was performed: inclusion criteria were adult age, reconnection surgery and SBS < 100 cm. Autologous gastrointestinal reconstruction represented an exclusion criteria. The outcomes of interest were the rate of total parenteral nutrition (TPN) independence and the length of follow-up (minimum 1 year) after surgery. We reviewed our experience from 2003 to 2013 with minimum 1-year follow-up, dealing with reconnection surgery in 13 adults affected by < 100 cm SBS after massive small bowel resection: autologous gastrointestinal reconstruction was not feasible. Three (out of 5168 screened papers) non randomized controlled trials with 116 adult patients were analysed showing weaning from TPN (40%, 50% and 90% respectively) after reconnection surgery without autologous gastrointestinal reconstruction. Among our 13 adults, mean age was 54.1 years (53.8 % ASA III): 69.2 % had a high stomal output (> 500 cc/day) and TPN dependence was 100%. We performed a jejuno-colonic anastomosis (SBS type II) in 53.8%, in 46.1% of cases without ileo-cecal valve, leaving a mean residual small bowel length of 75.7 cm. In-hospital mortality was 0%. After a minimum period of 1 year of intestinal rehabilitation, all our patients (100%) went back to oral intake and 69.2% were off TPN (9 patients). No one was listed for transplantation. A residual small bowel length of minimum 75 cm, even if reconnected to part of the colon, seems able to produce a TPN independence without autologous gastrointestinal reconstruction after a minimum period of 1 year of intestinal rehabilitation.

Surgery for post-operative entero-cutaneous fistulas: is bowel resection plus primary anastomosis without stoma a safe option to avoid early recurrence? Report on 20 cases by a single center and systematic review of the literature.

BACKGROUND: A review was performed on entero-cutaneous fistula (ECF) repair and early recurrence, adding our twenty adult patients (65% had multiple fistulas). METHODS: The search yielded 4.098 articles but only 15 were relevant: 1.217 patients underwent surgery. The interval time between fistula's diagnosis and operative repair was between 3 months and 1 year. A bowel resection with primary anastomosis was performed in 1.048 patients, 192 (18.3%) underwent a covering stoma: 856 patients (81.7%) had a fistula takedown in one procedure. RESULTS: The patients had 14.3% recurrence and 13.1% mortality rate. In our experience 75% were surgically treated after a period equal or above one year from fistula occurrence: surgery was very demolitive (in 40% remnant small bowel was less than 100 cm). We performed a bowel resection with a hand-sewn anastomosis (95%) without temporary stoma. In-hospital mortality was 0% and at discharge all were back to oral intake with 0% early re-fistulisation. CONCLUSIONS: Literature supports our experience: ECF takedown could be safely performed after an adequate period of recovery from 3 months to one year from fistula occurrence. In our series primary repair (bowel resection plus reconnection surgery without temporary stoma) avoided an early recurrence without mortality.

Home parenteral nutrition (HPN) in patients with post-bariatric surgery complications.

BACKGROUND & AIMS: Obesity is a worldwide health problem. Bariatric surgery (BS) is becoming one of the most commonly used methods for fighting obesity and its associated comorbidities. However, current BS techniques can be associated with early or late complications that may require nutritional support. The aim of this retrospective observational study was to determine the indications and outcomes for patients on Home parenteral nutrition (HPN) due to post-bariatric surgery complications. METHODS: A specific questionnaire was designed by the ESPEN HAN/CIF working group and submitted to HPN centers. This questionnaire included: patient demographics, type of surgery, BMI before surgery and at start of HPN, indications for HPN including technical and nutritional complications (early within 2 months after surgery or late), outcome, PN regimen, and HPN complications. Patients were retrospectively included from January 2008 to June 2014. RESULTS: Eighteen HPN centers responded to the survey. A total of 2880 HPN patients were treated during the study period, 77 of whom had BS (65 females; mean age 51 ± 7 years); gastric bypass was performed in 69% of the patients; mean BMI was 44.4 before surgery and 23.2 at the start of HPN. Indications for HPN were early complications in 17 cases and late complications in 60 cases. Early complications were mostly anastomotic leakage/fistula; late complications were hypoalbuminemia, and vitamin and trace element deficiencies. Out of 77 patients, 16 needed a surgical re-intervention, 29 were weaned off HPN, and 6 died (no HPN-related deaths). During the HPN period, 58% of the patients were re-hospitalized and central venous complications were observed in 41%. Diabetes mellitus was described in 17/77 patients. HPN was supportive in 60 patients and exclusive in 17 patients (mean caloric intake: 23 ± 6 kcal/k BW/day and 1.2 g/kBW/day). Only 7/77 patients resumed their professional activities on HPN. CONCLUSIONS: This is the largest observational multicenter study describing the use of HPN in patients with post-BS complications. Severe hypoalbuminemia is a major late complication. Rates of re-hospitalization and CVC infection were high. HPN may be a "bridge therapy" before surgical revision after BS. The high mortality rate reflects the complexity of these cases.

Development and validation of a nomogram to predict survival in incurable cachectic cancer patients on home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) in incurable cancer patients is extremely varied across different countries and institutions. In order to assess the clinical impact implied, we previously conducted a survey of incurable cancer patients receiving HPN, which shows that survival was markedly affected by Karnofsky performance status (KPS), tumor spread, Glasgow prognostic score (GPS) and tumor site. The aim of this study was to develop a nomogram incorporating the above factors for survival prediction. PATIENTS AND METHODS: We gathered a series of 579 patients, all receiving HPN, which was randomly split into a training and a testing sample. Using Cox proportional hazard regression modeling, a nomogram was built in the training sample, in order to estimate median survival or survival probability at 3 and 6 months according to individual patient characteristics. The nomogram performance was then verified in the testing sample. RESULTS: In the training sample, median survival was 3.2 (95% CI 3.0-3.7) months. GPS, KPS, tumor site and spread were confirmed to be significant prognostic factors. A significant interaction was also shown between the site and spread while weight loss (WL), adjusted for body mass index, failed to provide any substantial prognostic contribution. In the testing sample, nomogram performance was good in terms of calibration and discreet regarding discrimination. CONCLUSION: With the growing availability of new oncological treatments and their tendency to transform the trajectory of the advanced cancer into a chronic condition characterized by progressive WL and poor nutrients intake, an increasing number of patients are expected to receive HPN. In such a setting, tools for predicting the survival outcome may play a role toward personalized medicine and for investigating novel experimental therapies. Our proposed nomogram is a step forward in this direction but needs to be made stronger in order to definitely have clinical utility.

Long-term endoscopic follow-up in small bowel transplant recipients: single-center series.

BACKGROUND: The reliability of endoscopic findings after adult intestinal transplantation on short-term follow-up has been shown. The aim of this study was to evaluate in a long-term follow-up the diagnostic value of endoscopies compared with the biopsy value. METHODS: We evaluated 52 endoscopies over a period of 2 years (2 in each patient in 2010 and 1 in each patient in 2011, plus 1 endoscopy for suspected post-transplant lymphoproliferative disease [PTLD]) on 17 recipients transplanted between the years 2000 and 2006 (more than 5 years of follow-up). RESULTS: All the 52 endoscopic findings were comparable to biopsy definitive results: only 1 case of mild enteritis and 1 case of Epstein-Barr virus (EBV) chronic infection at biopsy were not diagnosed by endoscopy. One case of rectal PTLD and 1 of EBV-related enteritis were diagnosed by use of both procedures. Specificity was 98%: we did not calculate sensitivity because no episodes of rejection were diagnosed because recipients were stable in long-term follow-up. CONCLUSIONS: Endoscopy is a reliable procedure even on a long-term follow-up after intestinal transplantation, allowing a support to biopsy for diagnosis on adult recipients, especially for EBV infections and PTLD surveillance.

Alemtuzumab plus cyclosporine treatment of the autoimmune hemolytic anemia in an adult bowel transplant.

An adult male underwent a bowel transplant for tufting enteropathy, receiving alemtuzumab, tacrolimus, and steroids as immunosuppressants. Five years later, he developed an autoimmune hemolytic anemia (AIHA), anti-IgG positive, with reduced reticulocyte count, leukopenia, and thrombocytopenia with antiplatelet antibodies. After an unsuccessful initial treatment with high dose steroids, reduction in tacrolimus dose, and intravenous immunoglobulin (IVIG), a bone marrow biopsy revealed absence of erythroid maturation with precursor hyperplasia. The patient was switched to sirolimus and received four doses of rituximab plus two courses of plasmapheresis, which decreased his transfusion requirements. After a febrile episode one month later, the AIHA relapsed with corresponding decreases in platelet and leukocyte count: cyclosporine A (CsA) was started with a second course of rituximab and IVIG without response, even though repeat bone marrow biopsy did not reveal morphology correlated to an acquired pure red cell aplasia (APRCA). Considering the similarity in his clinical and laboratory findings to APRCA, alemtuzumab was added (three doses over a week) with CsA followed by steroids. The patient was eventually discharged transfusion-independent, with increasing hemoglobin (Hb) levels and normal platelet and leukocyte count. One year later he is still disease-free with functioning graft.

Disease-related intestinal transplant in adults: results from a single center.

Intestinal transplantation is gaining worldwide acceptance as the main option for patients with irreversible intestinal failure and complicated total parenteral nutrition course. In adults, the main cause is still represented by short bowel syndrome, but tumors (Gardner syndrome) and dismotility disorders (chronic intestinal pseudo-obstruction [CIPO]) have been treated increasingly by this kind of transplantation procedure. We reviewed our series from the disease point of view: although SBS confirmed results achieved in previous years, CIPO is nowadays demonstrating an excellent outcome similar to other transplantation series. Our results showed indeed that recipients affected by Gardner syndrome must be carefully selected before the disease is to advanced to take advantage of the transplantation procedure.

The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.

BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. RESULTS: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. CONCLUSIONS: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.

Operative endoscopy for treatment of native rectal post-transplantation lymphoproliferative disease after adult small bowel transplantation: a case report.

Post-transplantation lymphoproliferative disease (PTLD) of the gastrointestinal (GI) tract is often recognized in transplant recipients. Small bowel recipients are prone to develop GI disease due to the higher incidence of Epstein-Barr Virus (EBV) infection and enteritis as a consequence of heavy immunosuppressive regimens. So far treatment has been based on anti-CD20 therapy (Rituximab), modulation of immunosuppression, antiviral therapy (Gancyclovir), and surgery (up to allograft enterectomy if necessary), whereas endoscopy is usually used to perform the diagnosis via biopsy. We report a case of an adult small bowel recipient, who underwent transplantation due to Gardner's Syndrome 6 years earlier and was EBV positive. A native rectal PTLD was treated using opertive endoscopy combined with antiviral therapy using 4 courses of Rituximab for positive pelvic lymph nodes in addition to reduced immunosuppression. Two years after treatment the recipient is alive and disease-free with a functional graft.

Induction therapy in adult intestinal transplantation: reduced incidence of rejection with "2-dose" alemtuzumab protocol.

The incidence of early rejection after intestinal transplantation correlates with heightened risk of graft loss and mortality. Many different induction or pre-conditioning protocols have been reported in the last 10 yr to improve outcomes; however, sepsis remains prevalent and diminishes long-term results. We recently began a "2-dose" alemtuzumab trial protocol - 15 mg at day 0 and 15 mg repeated on day 7 - with the hope of reducing our infection rate. We compared three different protocols used at our institution (daclizumab, conventional "4-dose" alemtuzumab, and "2-dose" alemtuzumab). There was a significantly lower rate of early rejection with the "2-dose" alemtuzumab protocol in our study group of mainly (88%) intestinal grafts without accompanying liver engraftment with its protective immunologic effect. Sepsis remained low. Longer follow-up will be required to evaluate the effects of this new protocol on longer-term outcomes.

Mortality after steroid-resistant acute cellular rejection and chronic rejection episodes in adult intestinal transplants: report from a single center in induction/preconditioning era.

Steroid-resistant acute cellular rejection (ACR) and chronic rejection (CR) are still major concerns after intestinal transplantation. We report our experience from a single center on 48 adults recipients using 49 grafts from 2001 to 2011, immunosuppressing them initially with daclizumab initially and later Alemtuzumab. Overall patient survival was 41.9% at 10 years while graft survival was 38.5%. The steroid-resistant ACR population of 14 recipients (28.5%) experienced 50% mortality mainly due to sepsis, while the five (8%) CR recipients, included two survivors. All but 1 graft was placed without a liver. CR was often preceded by ACR episodes. Mortality related to steroid-resistant ACR and CR still affects the intestinal transplant population despite induction/preconditioning, especially in the absence of a protective liver effect of the liver. New immunosuppressive strategies are needed.

Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study.

BACKGROUND & AIMS: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. METHODS: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05 mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. RESULTS: PS reductions were associated with QoL improvements (ANCOVA, p = 0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100 cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. CONCLUSIONS: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo.

Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: rejection and infection rates in 40 recipients during the early postoperative period.

BACKGROUND: Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an important complication posttransplantation. Induction therapy has enabled improvement in graft and patient survival rates. OBJECTIVES: In analyze the effects of daclizumab and alemtuzumab as induction therapies on inflections complications and incidence of acute cellular rejection (ACR) during the early posttransplantation period. PATIENTS AND METHODS: Between December 2000 and August 2009, we performed 43 intestinal transplantation procedures in 42 adult recipients (median [SD] age, 34.8 [9.5] years; male-female ratio, 22:20; isolated or multivisceral graft, 32/11), and compared findings during the first 30 days posttransplantation in 40 recipients. Patients were divided into 2 groups: 12 treated with daclizumab (Zenapax; Hoffman-La Roche Ltd, Basel, Switzerland): 8 isolated intestinal grafts and 4 multivisceral grafts) and 28 treated with alemtuzumab (Campath-1H: 22 isolated intestinal grafts and 6 multivisceral grafts). Maintenance immunosuppression was based on tacrolimus and steroids in the first group and low-dose tacrolimus in the second group. RESULTS: During the first month posttransplantation, 8 daclizumab recipients (66.6%) experienced 9 episodes of mild ACR, which were successfully treated with steroid therapy, and 8 patients (66.6%) developed a bacterial infection requiring treatment. Fourteen episodes of ACR occurred in 12 alemtuzumab recipients (42.8%): 11 mild, 1 mild to moderate, and 2 moderate; 16 patients (57.1%) required treatment for infections. Five-year patient cumulative survival was 66% in daclizumab recipients and 43% in alemtuzumab recipients. Five-year graft survivals was 66% in daclizumab recipients and 41% in alemtuzumab recipients. In both groups, P was not statistically significative. CONCLUSIONS: The infection rate is considerably high with both protocols. Alemtuzumab seems to offer better immunosuppression against ACRs during the first month posttransplantation.

Comprehensive surgical intestinal rescue and transplantation program in adult patients: Bologna experience.

INTRODUCTION: Surgical approaches to complicated benign intestinal failure are accepted worldwide, especially in the pediatric population. Intestinal transplant surgery is thought to rescue patients in whom complications of total parenteral nutrition (TPN) develop. OBJECTIVE: To report our experience with surgical intestinal rescue in an adult population with intestinal failure. PATIENTS AND METHODS: An intestinal rehabilitation program initiated at our institution included comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. From 2000 to 2009, of 81 adult patients referred by our gastroenterologists for bowel rehabilitation, 42 (51,8%) underwent 43 transplantations (32 isolated intestinal grafts and 11 multivisceral grafts). Underlying diseases were primarily short-bowel syndrome, Gardner syndrome, and intestinal pseudo-obstruction. Thirty-nine patients (48,2%) underwent surgical rescue (40 cases) consisting of bowel resection, adhesiolysis, stricturoplasty, liver transplantation with portocaval hemitransposition (6 cases in 5 patients). Underlying diseases were primarily intestinal fistulas, stenosis, or perforations, short-bowel syndrome, cocoon syndrome, and complete portal thrombosis. RESULTS: After a mean (SD) follow-up of 1043 (1016) days, in the transplantation population, 21 patients (50%) are alive, with a 1-, 3-, 5-year patient survival of 76%, 59%, and 52%, respectively, and graft survival of 66%, 54%, and 48%, respectively. After 901 (404) days in the rescue population, 32 patients (82%) are alive (2 died, and 5 were lost to follow-up); in 75%, TPN 25% was discontinued, and are receiving oral feeding with TPN support. The 1- and 3-year survival rate was 100% and 83%, respectively. CONCLUSIONS: Deaths occurred primarily in the transplantation population. Intestinal surgical rescue, when possible, is optimal.

Italian experience in adult clinical intestinal and multivisceral transplantation: 6 years later.

PATIENTS AND METHODS: Between December 2000 and November 2006, 28 isolated intestinal transplants and nine multivisceral transplants (five with liver) from cadaveric donors have been performed for short gut syndrome (n = 15), chronic intestinal pseudo-obstruction (n = 10), Gardner's syndrome (n = 9), radiation enteritis (n = 1), intestinal atresia (n = 1), and massive intestinal angiomatosis (n = 1). Indications for transplantations were: loss of venous access, recurrent sepsis due to central line infection, and/or major electrolyte and fluid imbalance. Liver dysfunction was present in 19 cases. All patients were adults of median age at transplant of 34.7 years and mean weight 59.6 kg. All recipients were on total parenteral nutrition for a mean time of 38.8 months. Mean donor/recipient body weight ratio was 1.1. RESULTS: The mean follow-up was 892 +/- 699 days. Twenty-five patients were alive (67.5%) with 3-year patient survivals of 70% for isolated intestinal transplantations and 41% for the multivisceral transplantations (P = .01). The mortality rate was 32.5% with losses due to sepsis (63%) or rejection. Our 3-year graft survival rates were 70% for isolated intestinal transplantations and 41% for multivisceral transplantations (P = .02); graftectomy rate was 16%. These were 88% of grafts working properly with patients on regular diet with no need for parenteral nutrition. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the doses of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis, mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe acute chronic rejections.

Rejection episodes and 3-year graft survival under sirolimus and tacrolimus treatment after adult intestinal transplantation.

PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors have been recently introduced in clinical practice after intestinal transplantation. We focused on Sirolimus (Rapamycin) to examine effects on rejection and graft survival following intestinal transplantation. PATIENTS AND METHODS: Twenty isolated intestinal recipients and 5 multivisceral patients (2 with liver) in our series were divided into 3 groups: patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who continued therapy longer than 3 months (n = 11); patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who received therapy less than 3 months because of side effects (n = 4); and a control group, who never received rapamycin (n = 10). RESULTS: During prolonged treatment combined with Tacrolimus (Prograf), both Sirolimus groups showed a decreased number of acute cellular rejections (P < .01). Cumulative 3-year graft and patient survival rates were 81% in the Sirolimus greater than 3 months group, 100% in the Sirolimus less than 3 months group, and 80% and 90% in the control group, respectively (P = .63 and P = .62). CONCLUSION: In our experience, the use of mTOR-inhibitors in combination with calcineurin-inhibitors seemed to be more effective than monotherapy to reduce the number of rejections. Side effects can limit its use as maintenance therapy.

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

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; thymoglobulin 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. RESULTS: The mean hospital stay was 37 days. The mean follow-up 27 months. Twenty patients are alive (80%) with two- and five-yr patient survival rate of 80% and 66%; mortality rate was 20% due to sepsis in all cases. Our two- and five-yr graft survival rate is 76% and 64%, graftectomy rate was 16%. Sixteen grafts are working properly, with no need of parenteral nutrition. We diagnosed 35 mild acute cellular rejection (ACRs), seven moderate ACRs and three severe ACRs (two needed graftectomy). We experienced two episodes of chronic rejection biopsy-proven. Rapamicine was added in case of renal failure or biopsy-proven intestinal rejection. Graft-vs.-host disease was not seen in our series while post-transplant lymphoproliferative disease in two cases. After discharge, the most common indication for medical support was dehydration. The abdominal wall transplant did not experience any rejection. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the amount of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis and the mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe ACR.

Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: A comparison of two different regimens on 29 recipients during the early post-operative period.

INTRODUCTION: Induction therapy has been recently adopted for intestinal transplant. PATIENTS AND METHODS: We compared during first 30 days post-transplantation 29 recipients, allocated in two groups, treated with Daclizumab (Zenapax) or Alemtuzumab (Campath-1H). RESULTS: During first month, 45% of Daclizumab recipients experienced six acute cellular rejections (ACRs) of mild degree, while 63% of them developed an infection requiring treatment. We found three acute cellular rejections in 17.6% of Alemtuzumab recipients, two with moderate degree; 64.7% of them required treatment for infection. DISCUSSION AND CONCLUSIONS: Graft and patient 3-years cumulative survival rate were not significantly different between groups. Alemtuzumab seems to offer a better immunosuppression during first month.