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Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

We have studied cerebral blood flow velocity (CBFV) and cerebral autoregulation (CA) in 23 orthotopic liver transplantation (OLT) patients using transcranial doppler. CBFV was continuously recorded using a fixed (helmet) 2-Mz probe through the trans-temporal window. CA changes were studied using a linear regression analysis of percentile changes in CBFV and mean arterial blood pressure (MABP) after phenylephrine infusion compared with baseline. Pearson's “r” coefficient was considered an index of CA. In case of autoregulation is lost “r” tends to 1, thus representing complete dependence of CBFV on MABP. We regarded the slope coefficient parameter “S” as an index of cerebral vascular resistance (CVR), namely, the ratio of the corresponding variations of CBFV to MABP. Wilcoxon test showed a significant increase in both “r” and “S” between the anhepatic versus postreperfusion phases (within the first hour) and versus recovery in the neohepatic phase (end of surgery). A decreased CVR was observed within the first hour after graft reperfusion producing a loss of CA. These phenomena lead to an increase of CBFV and exposed the brain to hyperperfusion.

Background: To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. Methods: Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. Results: A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). Conclusion: Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability. © 2013 Editrice Gastroenterologica Italiana S.r.l.

Patients diagnosed with acute alcoholic hepatitis (AAH) are routinely managed medically and not considered suitable for orthotopic liver transplantation (OLT). The eligibility for OLT in these patients has been questioned due to the social stigma associated with alcohol abuse, based on the fact that AAH is "self-induced" with an unacceptably high recidivism rate. Many centers in Europe and the United States require abstinence periods between 6 and 12 months before OLT listing. AAH outcomes in the literature are poor, in particular due to patient noncompliance during the immediate 3 months preceeding OLT. Between January 1997 and December 2007, 246 patients were evaluated in our center for alcoholic liver disease: 133 (54%) were listed for OLT (I-OLT), including 110 (83%) who underwent transplantation and 8 (6%) still listed as well as 15 (11%) removed from consideration. One hundred thirteen (46%) patients had no indication for OLT (NO I-OLT), including 18 (16%) who died, 81 (71%) still monitored, and 14 (12%) lost to follow-up. Patient survival rates post-OLT were 79%, 74%, 68%, and 64% at 1, 3, 5, and 10 years, respectively. Explant (native liver) pathologic examination revealed AAH in 8 (7.2%) patients who underwent OLT. In this group, patient survival and the post-OLT recidivism rate were statistically identical to the overall group of transplant recipients.

Background & Aims: The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. Methods: We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. Results: 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p = 0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p = 0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p = 0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p = 0.0002), donor HBcAb positivity (1.56, p = 0.0015), recipient HBsAg positivity (0.43, p

Wilson's disease is a rare metabolic disorder that may lead to fulminant hepatitis and subsequent liver failure. Herein, we present a case of split liver transplantation performed on a patient with acute Wilson's disease. A 27-year-old female with acute presentation of Wilson's disease and advanced neurological impairment, received a Right Split liver Graft (Segments: IV, V, VI, VII and VIII) transplant. The graft was obtained by an in situ splitting technique. The graft implantation was performed in a standard fashion. No acute rejection episodes of the organ occurred. The postoperative course was uneventful. The graft function, ceruloplasmine level and copper levels progressively normalized. The patient totally recovered from neurological symptoms and the Kayser-Fleischer rings disappeared within one month. At 13 months of follow-up, the patient presented with no symptoms and in good condition. The current literature reports high preoperative mortality rate in patients that underwent partial liver graft for acute hepatic failure. However, our experience indicates that in situ split technique of liver may be a feasible and effective alternative to whole graft transplantation in urgent cases. Moreover, to our knowledge, this is the first successfully case of in situ split liver transplantation for acute Wilson's disease described in literature.

Primary splenic cysts are a rare finding. Some are large and require surgical removal. The Authors report a case of a recurrent huge splenic cyst in a 41-year-old female patient. A marsupialization was performed at another hospital 6 years before. Ultrasonography and computed tomography imaging revealed a cystic lesion in the spleen measuring approximately 20 cm in diameter. A total open splenectomy was performed. Postoperative course was uneventful. The histologic diagnosis was an epithelial cyst of the spleen with no atypical cells in the cyst wall, as previously found at the first operation. The epidermoid cysts have an epidermal lining, and prevention of recurrence is dependent on complete resection of the cyst wall preserving, whenever possible, the splenic tissue. Recurrence can be avoided with partial splenectomy in polar localization of the cyst, or complete removal of the cyst by "peeling" it off the splenic parenchyma. Marsupialization of the cyst, either via a laparoscopic or an open approach, is often ineffective.

Cystic lymphangioma is an uncommon benign pathology, usually reported in children, rarely in adult. Its embryopathogenesis is still controversial: it seems to arise from the lymphatic vessels, mainly in the cervico-cranial district. It is macroscopically characterised by multiple cystic non-communicating concamerations. Definitive diagnosis used to be intraoperative and was usually an unexpected finding. Nowadays, with modern imaging technologies, CT and MRI, diagnosis can be assumed before intervention even though certain diagnosis can still be reached only with histological examination. Imaging techniques can help for a precise mapping of the lesion and definition of its limits with the other structures, improving therapeutic success. Various therapeutical options are reported in literature, but complete surgical excision is still considered the best approach and the most successful. The Authors report their experience and review the literature on cystic lymphangioma in adult.

We analyzed, using a theoretical model, the modality of recurrence after a simple cruroplasty for large hiatal hernias, and on the basis of physical and geometrical principles, we conceived a new shaped mesh for a "tension-free" repair.We performed a physical and geometrical analysis of the hiatal region on a theoretical model. We also performed an anatomic study on 20 fresh cadavers to verify the reproducibility of the theoretical model and to study the most suitable shape for mesh and its adaptability to the hiatal region. Between September 2000 and October 2001, eight patients received laparoscopic reparation of large (type II or III) hiatal hernias by means of a composite "A"-shaped polytetrafluoroethylene (PTFE)-polypropylene mesh. There were two men and six women; mean age was 65 years (range, 35-78 years). Concomitant esophagitis was found in five patients and impaired esophageal peristalsis in two patients. A total or a partial fundoplication was associated in these cases.The physical and geometrical analysis of the hiatal region explained the reasons for the recurrence after hiatoplasty. The anatomical study on fresh cadavers resulted in a mesh tailored in an "A" shape and permitted to verify the adaptability of such a shaped mesh composed of two layers, polypropylene and PTFE. In the clinical series no conversions occurred; the mortality rate was null. Persistent dysphagia was present in two patients and disappeared after 3 months of treatment. No recurrence was observed at an 8-month average follow-up.The preliminary clinical study confirms the feasibility of this tension-free repair and the effectiveness of this composite A-shaped mesh.

The lack of organ availability and an increased number of end-stage cirrhotic patients has led to the lengthening of liver transplantation waiting lists. The progressive worsening of clinical and functional performance in patients awaiting the graft is one of the factors implicated in the increased mortality during the wait and in poor transplantation outcome. In this work our aim was to evaluate the effects of tauroursodeoxycholic acid administration on biochemical, clinical and functional parameters in a group of cirrhotic patients consecutively placed onto our liver transplantation waiting list.Ten cirrhotic patients underwent biochemical, clinical and functional evaluation at the time of entering on our liver transplantation waiting list, then tauroursodeoxycholic acid was administered until liver transplantation. Complete evaluation was repeated every 2 months. The results were compared to those of a comparable historical control group that had undergone liver transplantation the year before the study.All patients were transplanted within 6 months from insertion on the waiting list. Longitudinal analysis of the treated group showed that cholestasis and cytolisis parameters constantly decreased and that gamma-glutamyl transpeptidase was significantly lower compared to baseline values at the 4th month of therapy. Clinical and functional parameters remained stable during follow-up. Comparison with the control group showed that gamma-glutamyl transpeptidase, alkaline phosphatase and both aminotransferases were reduced at the 4th month of therapy. Fewer days of hospital stay and less intensive care were required in the treated group.Treatment of end-stage cirrhotic patients awaiting liver transplantation with tauroursodeoxycholic acid improves biochemical parameters of cytolisis and cholestasis, and furthermore helps to maintain clinical and functional stability during the wait. Improved biochemical conditions and steady clinical-functional performance may promote better short-term transplant outcome.

The purpose of this study was to determine the frequency and the outcome of de novo malignancies in a cohort of renal transplant paediatric patients. The records of 493 kidney transplants, carried out in 454 paediatric recipients at the three paediatric transplant centres of the North Italy Transplant programme (NITp, Italy) were reviewed. 10 cases of malignancies (2.2%) comprising both PTLD (post-transplant lymphoproliferative disorders) (6 cases, 1.3%) and non-PTLD malignancies (4 cases, 0.88%) were reported. Non-PTLD included one urothelial carcinoma and one Wilms' tumour of the recipient's left native kidney, one abdominal dysgerminoma and one optic nerve glioma of the left eye. The PTLD consisted of localised or disseminated Epstein–Barr virus (EBV)—associated B-lymphocyte monoclonal (5 cases) and polyclonal (1 case) proliferations. All patients suffering from PTLD had been EBV-negative at the time of transplantion, but developed EBV primary infection after transplantion. All PTLD patient donors were EBV-positive. In addition, all but 1 patient received, before and/or after transplantation, a range of immunosuppressive drugs in addition to the baseline prophylactic immunosuppressive regimen. Moreover, 3 patients suffered from syndromes associated with a genetic predisposition to cancer. Finally, the malignancies reported here were associated with 20% graft failure and 20% mortality rates.

In situ split-liver transplantation is a new surgical technique where the bipartition of a single liver allows procurement of a right graft (segments I, IV, V-VIII) for an adult recipient (75% of the total liver volume), and a left graft (segments II and III) for a child recipient. The present study was designed to assess the effects of ischemia-reperfusion on right grafts obtained by in situ split-liver transplantation. To this aim, hepatic glutathione and conventional plasmatic markers of allograft function (alanine and aspartate aminotransferase, total bilirubin, prothrombin time, lactate dehydrogenase, gamma-glutamyltranspeptidase, and alkaline phosphatase) were evaluated in four adult recipients. At the time of reperfusion, a marked glutathione decrease was found in the segment VI in three cases, whereas the amount of glutathione in segment IV was related to the duration of cold ischemia in all cases. Upon reperfusion, a marked increase in plasmatic alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase was found. A recovery in prothrombin time was observed from the first day in three cases. An increasing trend in total bilirubin, gamma-glutamyltranspeptidase, and alkaline phosphatase was noted from the second day after transplant. This preliminary study suggests a possible relationship between the duration of cold ischemia, amount of glutathione in segment IV of the right graft, and the trend in plasmatic markers of allograft damage during in situ split-liver transplantation in adult recipients.

Despite numerous advances in the areas of organ preservation, histocompatibility, and immunosuppression, chronic deterioration of organ allograft function, referred to as "chronic rejection," still remains the main obstacle to long-term graft survival. The common feature of chronic rejection is a concentric generalized graft arteriosclerosis associated with interstitial fibrosis that reflects an allogeneic injury to graft arteries, possibly worsened by other alloantigen-independent risk factors. The presence of the angiotensin I-converting enzyme (ACE) gene-deleted (D) allele has been associated, when in homozygosity, with increased risk of cardiovascular diseases and with an accelerated progression of organ damage in a variety of kidney diseases. In this study, we analyzed whether the insertion/deletion polymorphism of the ACE gene, because of its negative prognostic impact on cardiovascular and renal pathology, could have any influence on kidney graft survival in pediatric recipients.DNA was isolated from peripheral blood mononuclear cells from 146 pediatric dialysis patients (mean age: 12.9 years) who received a first kidney graft at our center between December 1985 and July 1997. To rule out any bias due to acute graft losses, only 119 patients who reached a minimum of 12 months of graft survival were considered for statistical analysis. The insertion/deletion polymorphism of the ACE gene was detected using a polymerase chain reaction technique with two flanking primers.The results demonstrated that (i) the distribution of DD and non-DD (ID + II) genotypes was 36.1% (43 patients) and 63.8% (76 patients), respectively; (ii) actuarial graft survival at 7, 8, 9, and 10 years in patients with non-DD genotype was significantly higher than that in patients with DD genotype (7 years: 94.6% vs. 72.4%, P0.05; 8 years: 94.6% vs. 62%, P0.025; 9 years: 87.3% vs. 51.4%, P0.025; 10 years: 76.3% vs. 25.7%, P0.01).In conclusion, the above data indicate that DD genotype is associated in pediatric kidney graft recipients with a shorter long-term kidney graft survival and suggest a possible role of this genotype as a cofactor in the progression of nonimmunological injuries leading to chronic kidney graft failure.

The authors analysed severe infections in 43 consecutive patients undergoing orthotopic liver transplant. Prophylaxis and full anti-infection monitoring was performed in all cases. Immunosuppressive therapy was administered in the form of primary cyclosporine in 27 cases and primary OKT3 in 16 cases.Twenty-seven patients are still alive (median 8 months, range 2-40) and 16 died (median 22 days, range 10-92) of whom 4 without and 12 with infection, including two deaths owing to non-correlated causes with infection after recovery. Twenty-three patients underwent 33 episodes of severe infection (plus four with inconclusive positive cultures) without any case of protozoal or viral infection. All episodes occurred within two months of surgery and affected the lung (10), abdomen (7), lung + abdomen (1), urinary tract (1), lung + urinary tract (1), as well as two diffused cases and 7 cases of isolated bacteremia deriving from the donor (1), venous catheters (3), mild otorhinolaryngeal infection (1) and two unknown sources (2). Eighteen infective agents were identified in 45 cases. The bacteria involved in single-agent episodes were: 11 Gram+, 9 Gram- and five fungi. Polymicrobic and bacterial/fungal episodes were repeatedly observed in two and two cases. Postoperative renal insufficiency significantly influenced both the incidence of and mortality due to infection. Overall mortality was also influenced by early graft function, postoperative complications and reoperations, and the incidence of infections by the portal clamping stage, reject and prolonged coma.The absence of severe viral infections and the gradual reduction of mortality caused by infection appear to be parallel to the aggressive antiviral prophylaxis, the gradual improvement of intra- and postoperative management and primary immunosuppression with OKT3.

The Authors report the case of a patient symptomatic for fever, weight loss and abdominal pain submitted to abdominal sonography and CT which identified a mass of the pancreatic head. The patient underwent laparotomy plus biopsy; the istologic and bacteriological diagnosis demonstrated a tuberculous lymphoadenitis in spite of a normal cutaneous tuberculin test. Abdominal localization of TBC infection therefore is increasing in epidemiological studies, and thus it must be included in the differential diagnosis of subdiaphragmatic disease.

The elevation of the uremic population age, the longer survival of dialysis, the increasing number of elderly donors, together with the safer surgical, anesthesiological and immunological procedures have led all over the word to an improvement of over 60s patients transplantation program, with very good results. The authors present their own experience of renal transplantation in elderly recipients and a review of what is reported in the literature on the question.

The chances of pregnancy for uremic women are usually very low, because of hormonal balance changes which determine a strong reduction in fertility. Epidemiological studies reveal that pregnancy in hemodialyzed women in fertile patients 4.6-6 months after a well functioning kidney transplant, one fertile transplanted woman over 50 can become pregnant. In the first transplant era, pregnancy after kidney transplant was considered "a big hazard", especially because of the possible side-effects of immunosuppression drugs on foetus development, and the risk of a worsening in the mother's renal function. Therefore, women were strongly recommended to avoid pregnancy. More recently, several reported papers have shown that pregnancy can be safely carried on also by transplanted women, under careful criteria and monitoring. Our experience too, even if limited in number (4 patients) reported in this article confirms this conviction.

The authors analyze results of 220 patients suffering from pancreatic cancer treated in their department from 1982 to 1992. Among these patients 24 of them underwent surgical operation for positioning of radioactive pills. The discussion is on indication and results of this technique, considering also what's reported in scientific literature on the argument.

The incidence of "de novo" cancers in kidney transplanted patients, especially because of immunosuppressive treatment, seems to be increased. The authors analyse their experience and review the literature.

The authors review their experience in the surgical management of rectal cancer. They analyze rectal malignancies and their recurrences from natural history to surgical strategies and survival rates. In particular, the need to perform extended operations in order to offer patients a better prognosis is discussed.

Multiple bile duct hamartomatosis of the liver or so-called von Meyenburg's syndrome, is an infrequent disease related to a dysembryogenic error. The authors discuss clinical features, diagnostic methods and possible related pathologies. Data reported in the literature are also received.

The contribution of different families of lymphocytotoxic antibodies in the serologic reactivity of 45 highly sensitized dialysis patients (HSDP) (panel reactivity antibody value-PRA greater than 80%) was assessed by analyzing patients' sera for the presence of auto- and alloreactive IgM and alloreactive IgG antibodies. A total of 220 sera was screened at different incubation temperatures, before and after treatment with the reducing agent dithiothreitol, against a large variety of cell targets by means of complement dependent cytotoxicity (CDC) and antiglobulin augmented (AHG) CDC assays. The results allowed to subdivide the HSDP under study into four groups: Group 1 consisted of 13 untransplanted patients and 14 patients with a prior failed graft whose PRA values did not change following DTT treatment. Alloreactive IgG antibodies alone, with anti-HLA specificity, were present in the sera of this patient group. Group 2 consisted of 3 untransplanted patients whose sera did not contain any autolymphocytotoxic antibody but appeared completely unreactive to panel lymphocytes following DTT treatment, thus confirming the presence of alloreactive IgM only endowed with antiHLA reactivity. Group 3 consisted of 4 untransplanted and 4 patients with a prior failed graft whose sera were found to contain in addition to autoreactive IgM also alloreactive IgG antibodies. Their PRA values declined after DTT treatment on average from 96.2% to 45% and from 95% to 52.5%, respectively. Group 4 consisted of 6 untransplanted patients whose PRA reactivity to both autologous and panel lymphocytes completely disappeared following DTT treatment, thus indicating that their sera contained exclusively autolymphocytotoxic IgM antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

HbsAg serum positivity in patients on the waiting list for kidney transplant and modifications of survival rate and transplanted kidney function deriving from this clinical situation are nowadays a matter of investigation and scientifical controversy. Authors analyse data deriving from their own series of renal transplant in HbsAg+ patients comparing them with literature.

Intestinal endometriosis is a rare lesion characterized by a difficult differential diagnosis with other intestinal diseases. The authors report the case of a woman suffering from endometriosis involving the distal ileal loop.

Carcinomas of the biliary tree present very difficult problems in diagnosis and treatment. Low common bile duct tumors, excluding papillary tumors, are rare but not easily detectable preoperatively and correctly treated. Authors report their clinical experience on the argument.

The evidence of thyroid vascular anomalies is is frequent and may manifest itself with an anatomic alteration. The absence of the inferior thyroid artery is reported in 1% of the cases, while a thyroid artery arising from the common carotid artery has been found in 2% of examined patients. In the observed case we retain that the rarity is not only due to the contemporary presence of two anomalies, but also to the presence of an anomalous vessel which arises from right carotideal bifurcation and bloody supplies either right lobular or left lobular of thyroid, thus resulting the sole gland's arterial vessel.

Several procedures for multiple cadaveric organ procurement have been developed for the recent growth of transplantation of extrarenal organs. These techniques permit removal of the kidneys, liver, pancreas and heart from the same donor without jeopardy to the kidneys above all. At the Department of Surgery - Section Transplantation of the University of Genoa in 1983 and 1984 19 multiple organ harvesting have been carried out. The kidneys were transplanted at our Center or at other Nit Center. Two patients received segmental pancreatic allograft. Two livers were sent to other Italian and European Centers and successfully transplanted.

Personal experience in the surgical management of the common bile duct is described. Over 100 cases of benign disease of the terminal choledocus are examined in a random assessment of 300 cases. The diagnostic and therapeutic techniques adopted are discussed.

The use of PTFE, vascular prosthesis (Gore-Tex), in the vascular access for hemodialysis, is a very reliable and exploited method. Thrombosis is the most frequent complication. The prosthetic "salvage operation" allows an immediate functional recovery. The authors examine their series from 1986 on, analyzing the surgical technics employed and the results obtained.