Lessons learned from 227 biological meshes used for the surgical treatment of ventral abdominal defects.

PURPOSE: The advantages of biological meshes for ventral hernia repair are still under debate. Given the high financial cost, the proper indications for biological meshes should be clarified to restrict their use to properly selected patients. METHODS: A retrospective database was instituted to register all cases of abdominal wall defect treated with biological meshes from 1/2010 to 3/2016. RESULTS: A total of 227 patients (mean age: 64 years) whose ventral abdominal defects were reconstructed with a biological mesh were included in the study. Patients were divided according to the 2010 four-level surgical-site complication risk grading system proposed by the Ventral Hernia Working Group (VHWG): Grade 1 (G1, 12 cases), Grade 2 (G2, 68 cases), Grade 3 (G3, 112 cases), and Grade 4 (G4, 35 cases). The surgical site complication rate was higher in patients with one or more risk factors (33.6% vs 19% in patients with no risk factors) (P = 0.68). Statistically significant risk factors associated with the onset of one or more postoperative surgical site complications included: diabetes, coronary artery disease, immunosuppression, and obesity. Recurrence was more common in patients with surgical site complications and mainly associated with infection (38.9%) and wound necrosis (44.4%), and in cases of inlay positioning of the mesh (36%). CONCLUSIONS: Due to their high costs, biological mesh should not be used in G1 patients. In infected fields (G4), they should only be used if no other surgical solution is feasible. There is a clear need to prospectively evaluate the performance of biological meshes.

AAV9-mediated engineering of autotransplanted kidney of non-human primates.

Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro. Serotype 9 was chosen for in vivo experiments owing to a lower frequency of preformed antibodies against the AAV9 capsid in 16 non-human primate tested sera. AAV9-LEA29Y was able to transduce the kidney of non-human primates in an autotransplantation model. Expression of LEA29Y mRNA by renal cells translated into the production of the corresponding protein, which was confined to the graft but not detected in serum. Results in non-human primates represent a step forward in maintaining the portability of this strategy into clinics.

Everolimus associated with low-dose calcineurin inhibitors, an option in kidney transplant recipients of very old donors.

BACKGROUND: Despite potential renal and cardiovascular advantages of proliferation signal inhibitors, their de novo use in kidney transplantation (KT) from elderly donors (ED) is poorly documented. We retrospectively analyzed two consecutive cohorts of KT from ED: low-dose extended-release tacrolimus (Tac) was used from 2010 to 2012 and cyclosporine (Csa) was used from 2008 to 2010. METHODS: Associated maintenance drugs were everolimus (Eve) and steroids. Outcomes were compared between groups over a 12-month follow-up. Fifty-six patients were analyzed in the Tac-Eve group and 54 in the Csa-Eve group. RESULTS: There were no significant differences at baseline with the exception of older donors age in the Tac-Eve cohort (74 vs 71 years, P = .002). There were no deaths, primary non functions, or graft losses. Eight (14%) Tac-Eve and 15 (28%) Csa-Eve patients had delayed graft function (P = .10). Renal function was fairly stable over time (median cGFR 36-49 mL/min and 51-55 mL/min in single kidney transplantation and dual kidney transplantation patients, respectively) with no significant differences between groups at month 12. Surgical complications were infrequent and observed mostly in dual kidney transplantation recipients. Thirty-nine (70%) and 30 (56%) patients remained under their initial Tac-Eve or Csa-Eve regimen, respectively. CONCLUSIONS: Induction with Thymoglobuline and maintenance with Eve and low-dose extended-release Tac and steroids is safe and effective in renal transplant from ED.

Refinement of a macaque transplantation model: application of a subcutaneous port as a means for long-term enteral drug administration and nutritional supplementation.

A new application of a device enabling the long-term enteral administration of drugs or nutritional supplementation was developed for implementing in research entailing the use of macaques (Macaca fascicularis). After implanting a subcutaneous port, a surgically-placed gastrostomy (SPG) was completed to afford access to the gastric lumen and enable the administration of substances. In this study, the device was left in place for a period ranging between two and 12 months in macaques (n= 16). In five cases, the SPG was used successfully for 8-12 months, until the experimental endpoint was reached. In six cases, the SPG had to be removed earlier due to local infection at the implant site, which promptly regressed after the SPG was removed and antibiotic treatment was administered. One SPG-implanted macaque was euthanized for reasons unrelated to the SPG or the xenotransplantation procedure. In four cases, the SPG was implanted without any complications but has yet to be used to administer substances to the animals. From an ethical standpoint, the SPG device described here minimizes the forced handling of macaques otherwise needed for the oral administration of viscous or unpalatable substances by gavage. The device thus represents an effective refinement that fully complies with the tenet of the '3 Rs' that should be considered by primate centres exposing non-human primates to the long-term daily administration of substances by oral gavage.

Technical aspects of unilateral dual kidney transplantation from expanded criteria donors: experience of 100 patients.

One option for using organs from donors with a suboptimal nephron mass, e.g. expanded criteria donors (ECD) kidneys, is dual kidney transplantation (DKT). In adult recipients, DKT can be carried out by several techniques, but the unilateral placement of both kidneys (UDKT) offers the advantages of single surgical access and shorter operating time. One hundred UDKT were performed using kidneys from ECD donors with a mean age of 72 years (Group 1). The technique consists of transplanting both kidneys extraperitoneally in the same iliac fossa. The results were compared with a cohort of single kidney transplants (SKT) performed with the same selection criteria in the same study period (Group 2, n = 73). Ninety-five percent of UDKTs were positioned in the right iliac fossa, lengthening the right renal vein with an inferior vena cava patch. In 69% of cases, all anastomoses were to the external iliac vessels end-to-side. Surgical complications were comparable in both groups. At 3-year follow-up, patient and graft survival rates were 95.6 and 90.9% in Group 1, respectively. UDKT can be carried out with comparable surgical complication rates as SKT, leaving the contralateral iliac fossa untouched and giving elderly recipients a better chance of receiving a transplant, with optimal results up to 3-years follow-up.

Laparoscopic live donor nephrectomy: single center experience.

AIMS: The aim of this study was a retrospective assessment of the safety of laparoscopic live donor nephrectomy (LLDN) and the outcome of these renal transplantations. METHODS: From November 2001 to October 2006, we performed 30 LLDN (all left nephrectomies) after excluding any renal vascular anomalies in the donor. All laparoscopic procedures were performed by a team consisting of an expert laparoscopic surgeon and a transplant surgeon. The donor mean age was 48.9 +/- 7.6 years (range 22 to 69), 33% of the donors were men and their mean Body Mass Index was 24.7 +/- 3.8 kg/m(2). The recipients were a 32 +/- 14 years old (range 6 to 64), with 66% of them men, and their mean time on dialysis, 33 +/- 49 months (range 0 to 120). RESULTS: After a mean follow-up of 39 +/- 14 months, all donors and recipients are alive. The mean operative time was 272 +/- 41 min (range 225-360) and the mean warm ischemia time, 161 +/- 35 seconds (range 107 to 240). Surgical complications in the donors were one incisional hernia and two cases of pneumonia. The donor's mean hospital stay was 5.3 +/- 1.7 days (range 3 to 12) and their mean serum creatinine at discharge was 111 +/- 21 micromol/L. There was one surgical complication-a hematoma-among the recipients, and all transplants functioned immediately except for one case. CONCLUSIONS: LLDN was confirmed to be safe and effective, with no negative impact on transplants success. Expertise in laparoscopic surgery is needed to minimize the side effects for the transplant donor and for the recipient.

Topical photodynamic therapy of actinic keratosis in renal transplant recipients.

Organ transplant recipients (OTRs) show an increased risk of precancerous (mostly actinic keratosis [AK]) and cancerous (mostly squamous cell carcinomas [SCC] and basal cell carcinomas [BCC]) cutaneous lesions. Their frequency increases with time after transplantation. AKs seem to progress more often and faster to invasive SCC in OTRs compared with the general population. The steady increase of risk of cutaneous premalignancies and malignancies with time after transplantation is an alarming figure because the number of organ allograft recipients who live for many years after transplantion is rapidly growing. This points out the need to devote more resources to skin cancer prevention, detection, and management. Various therapies, including cryotherapy, topical 5-fluorouracil, imiquimod, topical diclofenac, curettage, electrosurgery, carbon dioxide laser, and surgical excision, are available for AKs. However, most of these are limited by frequent relapses and the presence of multiple lesions over a wide area. Topical photodynamic therapy (PDT) represents an innovative therapeutic approach for nonsurgical treatment of cutaneous precancerous lesions and skin cancers. In this study we confirmed the usefulness of PDT in the treatment of AKs in OTRs, even in lesions relapsing or unresponsive to conventional treatment. We showed a complete response rate of 71%, after 2 treatments sessions that were 2 weeks apart. The response rate of scalp/facial lesions (72%) was higher compared with acral lesions (40%). Topical PDT could represent a useful therapeutic alternative for AKs in OTRs because large lesions can be treated with excellent cosmetic outcome.

Application of cyclosporine in renal transplantation: experience at the University of Padua.

Cyclosporine (CsA) therapy has evolved considerably since its introduction as the primary immunosuppressant drug in the early 1980s and its use in renal transplantation continues to expand globally. In the last 20 years, there have been significant advances in formulation design, therapeutic drug monitoring guidelines, and the emerging role of CsA-based combination therapies that have resulted in a substantial improvement in clinical outcomes in renal transplant recipients. The aim of this work is to review developments in the application of CsA in kidney transplantation at our Center in Padua and to evaluate the clinical outcome of our patients in the last 15 years in relation to the new trends in CsA management strategies.

Biphasic behavior of the kinetics of 31P-containing metabolites in ischemic porcine kidneys.

The assessment of kidney viability before transplantation (with a view of discarding nonviable organs) remains an obstacle to confidently extending organ harvesting to marginal donors. In the present study phosphorus magnetic resonance spectroscopy was used to monitor metabolic changes in (31)P-containing metabolites in isolated porcine kidneys. After various warm ischemia times, the organs were stored at 0 degrees C. Time-dependent changes in the phosphomonoester/inorganic-phosphate ratio were recorded at 0 degrees C were shown to follow a biexponential decay. The first-order kinetic rate constant of the short-time decay was strongly dependent on the warm ischemia time, a result that was discreted in terms of the underlying biochemistry. The metabolic events responsible for the dramatic decrease in phosphomonoester/inorganic phosphate ratio that occur immediately after organ perfusion and storage, suggest that any procedure to minimize organ damage must occur immediately after harvesting.

Deuterium nuclear magnetic resonance for evaluating the metabolic status of livers subjected to warm ischemia.

BACKGROUND: The development of reliable methods for assessing the viability of currently available livers is expected to increase the number of successful transplantations. METHODS: 2 H nuclear magnetic resonance (NMR) was used to search for metabolic markers of ischemia in explanted rat livers. Deuterium oxide (2 H2O) was used as a source of 2 H. A total of 10-80% v/v 2 H2O was added to homogenates obtained from a liver biopsy and the formation of 2 H-labeled metabolites was monitored. RESULTS: Some well-resolved 2 H resonances were found in the homogenates from biopsies of warm ischemic liver. Two of these were identified as [3-2 H] lactate and [2-2 H] lactate, and a linear relationship was found between the ratio of [[2-2 H] lactate] to [[3-2 H] lactate] and the warm ischemia time. The deuterium incorporation into lactate was explained on the basis of the metabolic events occurring under hypoxic conditions. CONCLUSIONS: The experimental results support the application of 2 H NMR for a reliable evaluation of the metabolic status of a liver harvested from non-heart-beating donors.

Warm hepatic ischemia in pigs: effects of L-arginine and oligotide treatment.

Reperfusion injury represents a key event leading to graft nonfunction. Maintaining adequate nitric oxide levels and stimulating vasodilator synthesis can probably minimize endothelial damage. The aim of this study was to investigate the effect of L-arginine, a substrate of nitric oxide synthesis, and oligotide, a promoter of prostacyclin synthesis, on liver function and morphology after warm ischemia-reperfusion injury. After constructing a side-to-side portacaval shunt, ischemia was induced by clamping the hepatic hilum for 2 h above the shunt, in 19 female pigs divided into a control group (n = 7), an L-arginine treatment group (n = 6), and an oligotide treatment group (n = 6). Liver function tests and measurements of serum and red blood cell malondialdehyde and plasma nitric oxide levels were performed before reperfusion and at 1, 10, 60, and 120 min after reperfusion. Liver biopsies, taken before reperfusion and at 30 min and 7 days after reperfusion, were analyzed for tissue malondialdehyde, histological-ultrastructural features, and apoptosis evaluation. Thirty minutes after reperfusion, liver malondialdehyde, sinusoidal congestion, necrosis, and apoptosis were significantly lower in the L-arginine group than in the controls (p < .05). On postoperative day 7, tissue malondialdehyde decreased, while plasma nitric oxide and hepatocyte glycogen content were increased in the L-arginine group compared to controls (p < .05). This study demonstrates the protective effect of L-arginine on hepatic lipoperoxidation and liver morphology in a pig model of warm ischemia-reperfusion injury. The increased plasma levels of nitric oxide a week after ischemia-reperfusion injury support the hypothesis that it has a role in preventing liver damage. The same beneficial effect was not confirmed for oligotide.

Mycophenolate mofetil (MMF) versus azathioprine (AZA) in pancreas transplantation: a single-center experience.

AIM: Advances in immunosuppression and careful monitoring for rejection are largely responsible for improved results in pancreas transplantation. We conducted a retrospective study to establish the effectiveness of immunosuppressive therapy with mycophenolate mofetil (MMF) instead of azatioprine (AZA) in pancreas transplantation and to assess adverse effects in the two different immunosuppressive regimes. SUBJECTS AND METHODS: Since 1991, 27 pancreas transplantations were performed in 25 patients at our Institute. For induction therapy, immunosuppressant protocol consisted of quadruple immunosuppressive therapy with cyclosporine, steroids, antilymphocyte globulin and AZA in 13 patients or MMF in 12 patients respectively. RESULTS: Acute rejection occurred in 76% of patients in the AZA group compared with 53% in the MMF group. Steroid-resistant rejection was observed in 7% in the MMF group compared to 38% of patients on AZA (p < 0.01). Two kidney grafts were lost due to acute rejection in the AZA group, one pancreas was lost due to acute rejection and one to chronic rejection in the MMF group. There were no significant differences in CMV infection. Severe fungal infections were noted in 2 patients treated with MMF. Malignancy occurred in 1 patient (pancreas graft lymphoma) in MMF. CONCLUSIONS: In conclusion, patients treated with MMF required less frequent and less intensive treatment for acute rejection. However, its short- and long-term side effects should be further investigated.