Massimiliano Veroux

Laparoscopic treatment of simple hepatic cysts and polycystic liver disease

Background: The authors present their experience in the laparoscopic management of hepatic cysts and polycystic liver disease (PLD). Methods: Between January 1996 and January 2002, 16 patients underwent laparoscopic liver surgery. Indications were solitary giant cysts (n = 10) and PLD (n = 6). Data were collected retrospectively. Results: Laparoscopic fenestration was completed in 15 patients. Median operative time was 80 min. There was no deaths. Complications occurred in four patients: one patient with a solitary liver cyst experienced diarrhea, while a pleural effusion, a bleeding from the trocar-insertion site, and ascites occurred in three patients with PLD. Median follow-up was 34 months. There was one asymptomatic recurrence (11%) in one patient with a solitary cyst. Two patients with PLD had a symptomatic recurrence of a liver cyst. Conclusion: Laparoscopic fenestration could be the preferred treatment of solitary liver cysts and PLD. Adequate selection of patients and type of cystic liver together with a meticulous surgical technique are recommended.

Infective Complications in Renal Allograft Recipients : Epidemiology and Outcome

INTRODUCTION Successful renal transplantation strictly depends on good control of rejection and better prevention and treatment of infections, which remain serious threats. METHODS This retrospective, observational study of 245 renal allograft recipients who underwent transplantation between January 2002 and December 2005 included a 21+/-10 months follow-up. RESULTS A total of 110 (44.9%) patients developed an infective process during the posttransplantation period, namely, 232 infective processes. Eighty patients developed at least 1 episode of urinary tract infection (UTI) 11 patients (4%) had a wound infection, and 30 patients (12%) had pneumonia. We diagnosed 35 cases of bacteremia (35%), whereas cytomegalovirus (CMV) infection was demonstrated in 40 patients (16%). CONCLUSIONS Immunosuppressive therapy, necessary to avoid acute and chronic rejection, exposes patients to a higher rate of infectious complications. The immunosuppressive protocols led to a relatively low incidence of infectious complications, mainly of little clinical significance. The highest incidence was evident by the sixth month after transplantation, when the immunosuppressive regimen exercised its most depressive effects on patient immune systems.

Genetically-Engineered Pig-to-Baboon Liver Xenotransplantation: Histopathology of Xenografts and Native Organs

Orthotopic liver transplantation was carried out in baboons using wild-type (WT, n = 1) or genetically-engineered pigs (α1,3-galactosyltransferase gene-knockout, GTKO), n = 1; GTKO pigs transgenic for human CD46, n = 7) and a clinically-acceptable immunosuppressive regimen. Biopsies were obtained from the WT pig liver pre-Tx and at 30 min, 1, 2, 3, 4 and 5 h post-transplantation. Biopsies of genetically-engineered livers were obtained pre-Tx, 2 h after reperfusion and at necropsy (4–7 days after transplantation). Tissues were examined by light, confocal, and electron microscopy. All major native organs were also examined. The WT pig liver underwent hyperacute rejection. After genetically-engineered pig liver transplantation, hyperacute rejection did not occur. Survival was limited to 4–7 days due to repeated spontaneous bleeding in the liver and native organs (as a result of profound thrombocytopenia) which necessitated euthanasia. At 2 h, graft histology was largely normal. At necropsy, genetically-engineered pig livers showed hemorrhagic necrosis, platelet aggregation, platelet-fibrin thrombi, monocyte/macrophage margination mainly in liver sinusoids, and vascular endothelial cell hypertrophy, confirmed by confocal and electron microscopy. Immunohistochemistry showed minimal deposition of IgM, and almost absence of IgG, C3, C4d, C5b-9, and of a cellular infiltrate, suggesting that neither antibody- nor cell-mediated rejection played a major role.

Late complication from a retrievable inferior vena cava filter with associated caval, aortic, and duodenal perforation: A case report

Inferior vena cava filters are an excellent therapeutic method for those patients in whom anticoagulant therapy is contraindicated or ineffective. However, filter placement is associated with a high rate of serious complications (>30%), with death occurring in 3.7% of patients. The most common complication is an asymptomatic inferior vena cava penetration and perforation. In some rare circumstances, however, therapeutic intervention may be required because of perforation of adjacent organs. We report a clinical case of a patient with simultaneous caval, duodenal, and aortic perforation resulting from penetration of inferior vena cava filter hooks. A brief review of the literature discusses presenting symptoms and treatment of such rare complications.

Pig‐to‐baboon heterotopic heart transplantation – exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade‐based regimens

Three costimulation blockade‐based regimens have been explored after transplantation of hearts from pigs of varying genetic backgrounds to determine whether CTLA4‐Ig (abatacept) or anti‐CD40mAb+CTLA4‐Ig (belatacept) can successfully replace anti‐CD154mAb.

Recipient obesity and outcomes after kidney transplantation: a systematic review and meta-analysis

BACKGROUND The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation. METHODS A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m(2). Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m(2)). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated. RESULTS Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83 416) and an increased likelihood of DGF (OR = 1.68, 95% CI = 1.39-2.03, studies = 4, n = 28 847). CONCLUSIONS Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.

Age is an important predictor of kidney transplantation outcome

BACKGROUND Donor and recipient age may have an impact on the renal transplant outcome. Kidney transplantation from older donors may result in a worse outcome, and the survival benefit of kidney transplantation compared with dialysis may be reduced. The aim of this study was to evaluate the impact of donor and recipient age on kidney transplant outcome. MATERIALS AND METHODS Two hundred and twenty-three recipients of kidney transplants performed at our institution between 2002 and 2007 were analysed. The role of donor and recipient age matching on survival rate were investigated performing the Kaplan-Meier survival time analysis by decades, considering the donors age of 60 and 70 years. The Cox proportional hazard uni- and multivariate regressions were also performed. Finally, Kaplan-Meier survival time analysis was performed to assess survival rates of patients transplanted stratified by donor age compared with wait-listed renal transplant candidates. RESULTS Elderly recipients had a significant lower graft and patient survival as well as a significantly higher risk of graft loss and patient death. Recipients younger and older than 65 years of age were at higher risk of graft loss if they received grafts from donors>65 years [hazard ratio (HR)=2.59, 95% confidence interval (CI): 1.12-6 and HR=5.65, 95% CI: 2.31-13.79, respectively]. Elderly recipients displayed a worse survival compared with transplant candidates on the waiting list. CONCLUSIONS Age is an important predictor of kidney transplantation outcome. Kidney transplantation does not offer a significant survival benefit in the intermediate term, compared to the waiting list, to elderly recipients transplanted with grafts from older donors. However, it cannot be excluded that it is still possible that there is a long-term benefit of transplantation over dialysis in this group of patients.

Surveillance of Human Papilloma Virus Infection and Cervical Cancer in Kidney Transplant Recipients: Preliminary Data

INTRODUCTION Development of cancer after transplantation has rapidly became one of the leading causes of death in kidney transplant recipients with functioning grafts. Anogenital malignant neoplasms may occur with a 14-fold increased incidence, and human papilloma virus (HPV) infection has been recently identified as the leading cause of cervical carcinoma. We report the preliminary findings of a prospective study that evaluated the incidence of HPV infection and cervical carcinoma in a population of kidney transplant recipients. PATIENTS AND METHODS The study included 35 female recipients of a deceased donor kidney with at least 6 months of follow-up. All patients underwent a cervicovaginal brushing, an HPV DNA test, and a Papanicolaou test. RESULTS Twenty-two patients (62.8%) were positive for HPV DNA. Thirteen of 22 HPV DNA-positive recipients (59%) demonstrated a high-risk HPV genotype. No cytologic anomalies were detected in Papanicolaou smears. CONCLUSIONS These preliminary data demonstrated a high incidence of HPV infection in renal transplant recipients. Most of our recipients exhibited a high-risk HPV genotype, which suggests higher aggressiveness of such infection in immunosuppressed patients. The HPV test is useful to monitor patients at higher risk of anogenital malignant neoplasms by identifying the cytologic anomalies at an earlier stage. This ongoing study will investigate the rate of progression of HPV infection and the clinical patterns of HPV-positive cytologic anomalies in renal transplant recipients.

Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.

BACKGROUND In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy. METHODS As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept + anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered. RESULTS When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response. CONCLUSION Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons.

Pregnancy under everolimus-based immunosuppression.

The ability to give birth to a live child is one of the best success of kidney transplantation. While there are an increasing number of pregnancies reported in kidney transplant recipients treated with cyclosporine or tacrolimus, there is little evidence of pregnancy among kidney transplant recipients exposed to sirolimus or everolimus. We present the first successful delivery in an organ transplant recipient exposed to everolimus during the whole gestation. The absence of congenital anomalies in the child as well as the recipient’s successful renal outcome are promising, although pregnancy in renal transplant recipients exposed to everolimus should be considered at higher risk.