[The correct evaluation of the microclimate for an ergonomic and safe workplace]. / La corretta valutazione del microclima per un luogo di lavoro ergonomico e sicuro.

In Italy, pursuant to Legislative Decree 81/08, the employer is obliged to assess all the risks to which workers are exposed. In this decree law, for the microclimate, there are few indications on how to carry out the assessment. No precise reference limits are set but it is only recommended to adapt the environmental conditions to the physical effort carried out, the parameters that need to be measured and with which instruments and who can carry out the measurements and therefore the related assessments are not specified. The technical reference standard is instead well established and proposes evaluation indices that take into account the heat exchanges between the human body and the thermal environment and allow to prevent discomfort or even damage to health. However, it is necessary for the evaluator to use these indices correctly to avoid underestimating risky conditions. This work aims to provide a guide to those who are preparing to evaluate the thermo-hygrometric conditions of a workplace. The assessors must choose the path based on the activity carried out in the workplace and its physical characteristics, using the measurement equipment required by the technical regulations and verify its reliability. An incorrect assessment can make people underestimate the discomfort which is often associated with a lowering of the level of attention and therefore a predisposition to accidents, or it can expose workers to serious health risks.

[Radon exposure: also in this case it is better to open the window]. / Esposizione al Radon : anche in questo caso è meglio aprire la finestra.

Although many areas of the Italian territory are of volcanic origin, there is not much attention to the prevention of risks due to exposure to Radon gas. This gas is produced during the decay of uranium present in volcanic rocks and, if inhaled, its further decay produces radioactive radiation responsible for damage to lung tissues. It is estimated that these radiations are responsible for 10% of lung cancers. In conditions of poor air exchange, the concentration of Radon gas can easily reach high concentrations, particularly in underground rooms or on the ground floor that are in direct contact with the ground. In these territories, the designers of new buildings do not always consider this risk and the population is also poorly informed on the behavior to be adopted for prevention.

Impact of preoperative infection on outcome after liver transplantation.

BACKGROUND: Bacterial infection in patients with liver failure can lead to a dramatic clinical deterioration. The indications for liver transplantation and outcome in these patients is still controversial. METHODS: All adult patients who underwent liver transplantation between 1 January 2010 and 31 December 2015 were selected from an institutional database. Characteristics of the donors and recipients, and clinical, biochemical and surgical parameters were retrieved from the database. Post-transplant survival rates and complications, including grade III-IV complications according to the Dindo-Clavien classification, were compared between patients with an infection 1 month before transplantation and patients without an infection. RESULTS: Eighty-four patients with an infection had statistically significant higher Model for End-stage Liver Disease (MELD), D-MELD and Balance of Risk (BAR) scores and a higher rate of acute-on-chronic liver failure compared with findings in 343 patients with no infection. The rate of infection after liver transplantation was higher in patients who had an infection before the operation: 48 per cent versus 30·6 per cent in those with no infection before transplantation (P = 0·003). The percentage of patients with a postoperative complication (42 versus 40·5 per cent respectively; P = 0·849) and the 90-day mortality rate (8 versus 6·4 per cent; P = 0·531) was no different between the groups. Multivariable analysis showed that a BAR score greater than 18 and acute-on-chronic liver failure were independent predictors of 90-day mortality. CONCLUSION: Bacterial infection 1 month before liver transplantation is related to a higher rate of infection after transplantation, but does not lead to a worse outcome.

Kidney preservation: review of present and future perspective.

One of the main problems in transplant surgery is the preservation of the organ during the cold ischemic time. The interrupted blood supply triggers a cascade of biological modifications resulting in cell death, which predisposes to discharge of a large quantity of toxic metabolites at the moment of organ reperfusion. Many approaches have been studied to prevent the toxic processes. Immediately after procurement, kidneys are flushed with these solutions. Two main: techniques of organ preservation are cold static storage and hypothermic machine perfusion (HMP). Based on age and comorbidities, individuals can be generally divided into 2 groups: ideal and marginal donors. Characteristics of organs from marginal donors are associated with an increased rate of delayed graft function and primary graft nonfunction (PNF), which reduce transplant survival and increase the acute rejection risk. In the last 20 years, the United Network of Organ Sharing has reported a 170% increase in deceased donors older than 50 years of age. Techniques of perfusion have been demonstrated to play a pivotal role in graft function after transplantation. Some studies suggest that HMP may improve outcomes after transplantation.

Induction therapy with alemtuzumab (campath) in combined liver-kidney transplantation: University of Bologna experience.

BACKGROUND: Combined liver-kidney transplantation (LKT) is considered to be a safe procedure, but the appropriate immunosuppressive regimen is unclear. PATIENTS AND METHODS: Between January 1997 and October 2011, 55 patients were listed for LKT: 45 (82%) were effectively transplanted, 5 (9.2%) died whereon here the waiting list, 3 (5.5%) temporarily out of waiting list, 1 (1.8%) was on waiting list and 1 (1.8%) refused LKT. Five LKTs treated with cyclosporine (CyA) were excluded from the analysis. Mean recipient age was 50.32 ± 10.32 years (14-65), MELD score at time of LKT was 19.22 ± 4.69 (8-29), mean waiting list time was 8.14 ± 9.50 months (0.1-35.76), and follow-up, 4.09 ± 3.02 years (0.01-10.41). Main indications for LKT were policystic disease (n = 15; 37%), hepatitis virus C (HCV)-related cirrhosis (n = 9; 22%) metabolic disease (n = 5; 13%), hepatitis virus B (HBV) cirrhosis (n = 4; 10%), alcoholic cirrhosis (n = 4; 10%), and cholestatic disease (n = 3; 8%). Immunosuppressive regimen was based on tacrolimus and steroids in 40 cases with induction therapy with alemtuzumab (Campath; 0.3 mg/kg) in 13 of 40 instances cases administered on day 0 and day 7. RESULTS: Postoperative mortality was 2.5%. Acute cellular rejection episodes were biopsy-proven in 2 (5%) cases, post-LKT infections developed in 17 cases (42.5%), and de novo cancer developed in 3 (7.5%) cases. Similar 5-year overall survivals were obtained irrespective of the LKT indication: 100% in cholestatic and alcoholic cirrhosis patients, 86% in policystic disease, 75% in metabolic disease and HBV patients, and 66% in HCV cirrhosis. Overall survivals for the alemtuzumab vs without-induction therapy groups at 1, 3, and 5-years were 100%, 85.7%, and 85.7% vs 76%, 76%, and 70%, respectively (P = .04). CONCLUSION: An immunosuppressive regimen based on tacrolimus and steroids with induction therapy with alemtuzumab was safe, with excellent long-term results for combined LKT.

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.

Importance of renal mass on graft function outcome after 12 months of cadaveric donor kidney transplantation.

BACKGROUND: Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation. METHODS: We evaluated 81 renal transplantation recipients from cadaveric donors. We collected donor and recipient demographic, clinical and anthropometric data. Data about kidney weight were obtained through kidney measurement using an electronic machine at the moment of transplantation. RESULTS: The mean kidney weight was 201.4 +/- 10.2 g (200.5 +/- 11.6 g in women and 210.3 +/- 14.1 g in men). Kidney weight correlated with CrCl at 12 months (0.001). The CrCl at 12 months showed a significant correlation of graft weight/recipient weight ratio (P < .01). CONCLUSION: The cadaveric donor kidney weight significantly influenced the CrCl at 12 months after transplantation.

Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma.

Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.

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.

Psychological adaptation and quality of life of adult intestinal transplant recipients: University of Bologna experience.

INTRODUCTION: Intestinal transplantation has become an accepted therapy for individuals permanently dependent on total parenteral nutrition (TPN) with life-threatening complications. Quality of life and psychological well-being can be seen as important outcome measures of transplantation surgery. METHODS: We evaluated 24 adult intestinal transplant recipients and 24 healthy subjects (a control group). All subjects were administered the Italian Version of the Psychological Well-Being Scales (PWB) by C. Ryff, the World Health Organization Quality of Life-Brief (WHOQOL), and the Symptom Questionnaire (SQ) by R. Kellner and G.A. Fava, a symptomatology scale. Quality of life and psychological well-being were assessed in transplant recipients in relationship to the number of rejections, the number of admissions, and the immunosuppressive protocol. RESULTS: Intestinal transplant recipients reported significantly higher scores in the "personal growth" category (P = .036) and lower scores in the "positive relation with others" (P = .013) and "autonomy" (P = .007) dimensions of PWB, compared with the controls. In the WHOQOL, the scores of transplant recipients were lower only in the psychological domain (P = .011). Transplant recipients reported significantly higher scores in the "somatic symptom" (P = .027) and "hostility" (P = .018) dimensions of the SQ, compared with the controls. Transplant recipients with number of admissions >8 reported higher scores in "anxiety" (P = .019) and "depression" (P = .021) scales of the SQ, and the patients with a Daclizumab protocol reported higher scores in "depression" (P = .000) and "somatic symptom" (P = .008) of the SQ. There were no significant differences regarding number of rejections and socio-demographic variables. CONCLUSION: Improvement of psychological well-being in the transplant population may be related to the achievement of the goal of transplantation: recovery of bowel function. But the data confirmed that the transplant experience required a long and difficult adaptation trial to the new condition of "transplant recipient."

[Pancreatic carcinoma presenting with invasion of the vena porta or the superior mesenteric vein: our experience and review of the literature]. / Carcinoma del pancreas con infiltrazione della vena porta o della vena mesenterica superiore: nostra esperienza e revisione della letteratura.

AIM: Adenocarcinoma of the pancreas can present with invasion of the vena porta or the superior mesenteric vein (SMV). Pancreatectomy with resection of the vena porta and/or the SMV remains controversial although the procedure is potentially curative. The aim of this study was to validate the indication for resection on the basis of our experience and evidence from recently published studies. METHODS: Studies published in the last 10 years on pancreatectomy (duodenocephalopancreatectomy, total and distal pancreatectomy) with resection of the vena porta and/or the SMV were retrieved from the Medline database and reviewed. A total of 18 studies meeting the inclusion criteria were analyzed for information about indications, type of intervention, use of adjuvant therapies, histopathology, perioperative results and survival in 620 patients with adenocarcinoma of the pancreas undergoing pancreatectomy with resection of the vena porta and the SMV. This data set was then compared with our experience with this procedure from the last 3 years. RESULTS: The mortality and postoperative complication rates varied between 0% and 7.7% and 12.5% and 54%, respectively. The median survival varied from 12 to 22 months; the 1 year survival rate was between 31% and 83%; the 5-year survival rate was between 9 and 18% according to the studies reviewed. CONCLUSION: On the basis of evidence from the literature and our experience, en bloc resection of the vena porta and/or the SMV during pancreatectomy appears to be a safe procedure with acceptable outcomes, and should be considered in patients with pancreatic cancer presenting with venous invasion. Venous resection increases the surgical cure rate, prolonging survival in patients selected according to correct indications.

The role of liver surgery in the treatment of non-colorectal non-neuroendocrine metastases (NCRNNE). Analysis of 134 resected patients.

AIM: The aim of this study was to evaluate the role of surgery in the treatment of non-colorectal, non-neuroendocrine (NCRNNE) liver metastases. METHODS: One hundred and thirty-four patients undergoing curative liver resection for NCRNNE liver metastases were retrospectively analyzed. Perioperative results (blood transfusion, hospital stay, morbidity and mortality), 3 and 5-year overall and disease-free survival were evaluated. The following prognostic factors were analyzed: age (cut-off 50 year old), single vs. multiple nodules, diameter (cut-off 5 cm), disease-free interval less vs. more than one year, type of primary tumor, blood transfusion, major hepatectomy vs. minor hepatectomy. Survival of patients undergoing liver resection for metastatic colorectal cancer was also analyzed to compare the results with the study population. RESULTS: Mortality and morbidity rate were 3% and 23.1%, respectively. The 3 and 5-year survival were 56.5% and 40%, respectively. The 3 and 5-year disease-free survival were 44% and 30%, respectively. Diameter, disease-free interval and metastases from gastrointestinal cancers were independently related to the survival at the multivariate analysis. Thirty-nine patients (27%) survived over five years. Patients with liver metastases from gastrointestinal primary tumors were those with a worse survival (25% and 19% at 3 and 5 years, respectively). CONCLUSIONS: Surgery is an effective treatment for patients with NCRNNE liver metastases, providing satisfactory long-term outcomes with acceptable morbidity and mortality, in particular when excluding patients with gastro-intestinal metastases.

Clinical trial: peg-interferon alfa-2b and ribavirin for the treatment of genotype-1 hepatitis C recurrence after liver transplantation.

BACKGROUND: Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates. AIM: To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response. METHODS: Fifty-three patients with post-LT HCV recurrence were enrolled. Patients received PEG-IFN alfa-2b 1.0 micro/kg/week plus RBV 8-10 mg/kg/day for 24 weeks. Those with 'early virological response at week 24' (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C). RESULTS: Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV-RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02-106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end-of-treatment response. One patient in group B had SVR. CONCLUSIONS: Pegylated-interferon alfa-2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with > or =2 log10 drop in HCV-RNA at week 24.

Liver transplantation for recurrent hepatocellular carcinoma on cirrhosis after liver resection: University of Bologna experience.

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.

[Hepatic resections for hepatocarcinoma in the XXI century]. / Le resezioni epatiche per epatocarcinoma nel XXI secolo.

Hepatic resection is today the treatment of choice for cirrhotic patients affected by hepatocellular carcinoma (HCC). Short term results are now definitely satisfactory, with a mortality rate in the referral centers lower than 5%. However, long term results are affected by a high recurrence rate, between 50% and 100%, due to the underlying cirrhosis. Notwithstanding the high recurrence rate, the hepatic resection guarantees a five years survival between 40% and 60%, comparable to the one offered by liver transplantation. The aim of this paper is to review the results of studies on resected cirrhotic patients affected by HCC.

Coping strategies in intestinal transplantation.

The psychological construct of coping has been studied extensively in other medical populations and has more recently been applied in the field of transplant psychology. Coping can be defined as all abilities used by people to face problematical and stressful situations, as the data in literature describe the experience of transplantation. The purpose of this study was to describe the coping styles used by 25 intestinal transplant recipients. To assess the coping strategies, we used the Italian version of Coping Orientation to Problems Experienced (COPE) by Sica, Novara, Dorz, and Sanavio (1997). The authors divided these strategies into three classes: problem-focused, emotion-focused, and potentially disadaptive strategies. This questionnaire is usually used in a medical setting. Even if the long process of psychological-clinical adaptation required by intestinal transplantation put patients in a passive acceptance of their situation and their incapacity to face it, our patients showed high levels of problem-focused strategies, indicators of positive outcomes for this intervention. Anyway, this is a slow and gradual path that goes with the psychological distress and the need for a peculiar psychological support of problem-focused strategies. The result suggested that assessment of coping strategies should be explored in intestinal transplant to encourage the use of action-oriented methods and discourage those with possible negative effects.

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.