Fabio Vistoli

Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose.

Decreased beta‐cell mass, mainly due to apoptosis, is crucial for the development and progression of type 2 diabetes. Chronic exposure to high glucose levels is a probable underlying mechanism, whereas the role of oral anti‐diabetic agents (sulphonylureas in particular) is still unsettled.

Kidney preservation with university of Wisconsin and Celsior solution: a prospective multicenter randomized study.

Background. Although the University of Wisconsin (U.W.) solution continues to be the most commonly used for intra-abdominal organs, a new solution, Celsior, already used for heart and lungs, has been proposed for kidney and liver preservation. The aim of this research was to assess the effect of Celsior as compared with U.W. on immediate graft function and a 2-year follow-up of kidney transplants. Methods. A prospective multicenter randomized study was designed to evaluate the efficacy of the Celsior solution in the clinical preservation of the kidney. In this report, we present the data collected as of September 2000. One hundred donors were included in the trial resulting in 187 renal transplants. Ninety-nine kidneys were stored in Celsior solution and 88 in U.W. solution. The groups were comparable with regard to donor and recipient characteristics. Results. Delayed graft function occurred in 31.3% of the Celsior group and in 33.9% of the U.W. group (P =n.s.). Mean serum creatinine levels and mean daily urinary output were also comparable. Two year graft survival in kidneys preserved with Celsior was 84% as compared with 75% for U.W.-preserved kidneys without any significant statistical difference. Conclusions. Our data show that the preservation of kidneys in Celsior solution in a clinical setting is equivalent to that of U.W. solution. When using Celsior during multiple-organ donor harvesting it would be possible to perform an in situ flush of all intra-abdominal and intrathoracic organs with a single cold storage solution.

Effects of pancreas-kidney transplantation on diabetic retinopathy

The effects of pancreas transplantation (PTx) on diabetic retinopathy (DR) are still debated. We studied the course of DR in 48 patients (age: 40 ± 7 years; males/females 26/22, body mass index (BMI): 23.0 ± 2.4 kg/m2, duration of diabetes: 24 ± 8 years) bearing a successful PTx (combined with a kidney). Follow‐up ranged 6–60 months (median: 17 months). Before transplantation, according to the Eurodiab Study classification, 12 patients (25%) had nonproliferative retinopathy (NPDR; mild, moderate or severe), and 36 patients (75%) had laser‐treated and/or proliferative retinopathy (LT/PDR). During the follow‐up, in the NPDR group improvement/deterioration was defined as regression/progression to a lower/higher retinopathy grade; in the LT/PTD group, stabilization was defined as no new neo‐vessel formation or development of new lesions requiring laser‐treatment. In the NPDR group, five (41.7%) patients improved of one or more lesion grading, three (25%) patients showed no change, and four (33.3%) patients progressed of one grade. In the LT/PDR group, the post‐transplant data were: stabilization in 35 (97%) patients, and worsening in one (3%) patient. The number of improved/stabilized patients was significantly higher in the transplanted than in a control group of nontransplanted type 1 diabetic patients. In conclusion, despite a relatively short follow‐up period, successful PTx in our cohort of patients was associated with improvement and/or stabilization of DR in the majority of recipients.

Robotic renal transplantation: first European case

A kidney from a 56‐year‐old mother was transplanted to her 37‐year‐old daughter laparoscopically using the daVinci HDSi surgical system. The kidney was introduced into the abdomen through a 7‐cm suprapubic incision used also for the uretero‐vescical anastomosis. Vascular anastomoses were carried out through a total of three additional ports. Surgery lasted 154 min, including 51 min of warm ischemia of the graft. Urine production started immediately after graft reperfusion. Renal function remains optimal at the longest follow‐up of 3 months. The technique employed in this case is discussed in comparison with the only other two contemporary experiences, both from the USA. Furthermore, possible advantages and disadvantages of robotics in kidney transplantation are discussed extensively. We conclude that the daVinci surgical system allows the performance of kidney transplantation under optimal operative conditions. Further experience is needed, but it is likely that solid organ transplantation will not remain immune to robotics.

Posttransplant Donor-Specific Anti-HLA Antibodies Negatively Impact Pancreas Transplantation Outcome

During a 9‐year follow‐up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreas‐kidney [SPK]) were followed for the detection of posttransplant anti‐HLA antibodies. Forty patients (24%) developed anti‐HLA antibodies, 26 (65%) had donor‐specific antibodies (DSA; 61% anticlass 2) and 14 (35%) non‐DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti‐HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non‐DSA (p < 0.05) or to negative patients (p < 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti‐HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non‐DSA positive patients (100% for pancreas and 92% for kidney) or to HLA‐negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti‐HLA patients (32.5% vs. 11%; p < 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.

Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients

Background. The effects of pancreas transplant alone (PTA) on cardiovascular risk factors (CRF) and cardiac function in type 1 diabetes mellitus (T1DM) patients are still unsettled. Methods. We studied 13 T1DM patients who received PTA with portal drainage and 11 matched control patients. Parameters of glucose and lipid metabolism and several additional classic CRF were assessed before and up to 6 months posttransplant. Cardiac morphology and function were assessed by Doppler echocardiographic examination. Results. Insulin independence was promptly achieved and then maintained after PTA. Total and low-density lipoprotein cholesterol levels were significantly lower after transplantation, whereas high-density lipoprotein cholesterol and triglyceride concentrations did not change. Both systolic and diastolic blood pressure values and fibrinogen levels improved significantly. In addition, PTA determined a significant amelioration of several morphologic and functional cardiac indices. None of the measured parameters changed in the control patients. Conclusions. PTA with portal drainage induces an early improvement of CRF and ameliorates cardiac function in patients with T1DM.

Laparoscopic Robot-Assisted Pancreas Transplantation: First World Experience

Background. Surgical complications are a major disincentive to pancreas transplantation, despite the undisputed benefits of restored insulin independence. The da Vinci surgical system, a computer-assisted electromechanical device, provides the unique opportunity to test whether laparoscopy can reduce the morbidity of pancreas transplantation. Methods. Pancreas transplantation was performed by robot-assisted laparoscopy in three patients. The first patient received a pancreas after kidney transplant, the second a simultaneous pancreas kidney transplantation, and the third a pancreas transplant alone. Operations were carried out through an 11-mm optic port, two 8-mm operative ports, and a 7-cm midline incision. The latter was used to introduce the grafts, enable vascular cross-clamping, and create exocrine drainage into the jejunum. Results. The two solitary pancreas transplants required an operating time of 3 and 5 hr, respectively; the simultaneous pancreas kidney transplantation took 8 hr. Mean warm ischemia time of the pancreas graft was 34 min. All pancreatic transplants functioned immediately, and all recipients became insulin independent. The kidney graft, revascularized after 35 min of warm ischemia, also functioned immediately. No patient had complications during or after surgery. At the longer follow-up of 10, 8, and 6 months, respectively, all recipients are alive with normal graft function. Conclusions. We have shown the feasibility of laparoscopic robot-assisted solitary pancreas and simultaneous pancreas and kidney transplantation. If the safety and feasibility of this procedure can be confirmed by larger series, laparoscopic robot-assisted pancreas transplantation could become a new option for diabetic patients needing beta-cell replacement.

Robotic suture of a large caval injury caused by endo-GIA stapler malfunction during laparoscopic wedge resection of liver segments VII and VIII en-bloc with the right hepatic vein

Primary endo-GIA stapler malfunction occurred during robotic wedge resection of liver segments VII and VIII en-bloc with the right hepatic vein, in an obese woman diagnosed with single liver metastasis from a previous carcinoid tumour. Haemorrhage was soon controlled by clamping the vena cava below the injury using two wristed forceps angled at 90°. With the two instruments locked in the holding position the ensuing operative strategy was discussed between surgeon and anaesthesia teams. Using the third robotic arm the caval injury was repaired laparoscopically with interrupted polypropylene sutures. The patient was transfused with two units of packed red blood cells, recovered uneventfully, and was discharged on post-operative day five. We conclude that even the most advanced technologies can fail and that surgeons should be fully aware of the consequences of these malfunctions and be prepared for repair. From this point of view, the da Vinci surgical system seems to have some advantages over classical laparoscopic methods including the ability to lock the wristed instruments in the holding position, the use of three arms by the same operating surgeon, and the extreme facilitation of intracorporeal suturing and knot-tying in deep and narrow spaces, extremely difficult if not impossible with conventional laparoscopic instruments.

Minimization protocols in pancreas transplantation

Diagnosis of immunologic injury (acute and chronic) is much more difficult in pancreas transplants when compared with transplants of other organs. Currently, the immunosuppressive regimen for induction involves calcineurin inhibitors (CNI), antimetabolites and corticosteroids (Cs). This strong and nonspecific regimen does not take into consideration pancreas specificities (i.e. the need to avoid diabetogenic compounds). For obvious reasons, CNI might be calling for review, if permanently indicated in recipients of solitary pancreas with mild renal dysfunction. CNI as well as corticosteroids may induce hyperglycemia and contribute to differential diagnosis of a rejection process. However, in spite of the benefits accruing from withdrawal of above immunosuppressive agents, minimization or avoidance of these drugs could be dangerous and may end up with graft loss (i.e. antibody‐mediated process). Long‐term results of pancreas transplantation are now achieving comparable survival rates similar to the transplant of traditional organs such as kidney and liver. As a consequence, the physicians’ objectives are to prolong the patient’s quality of life and organ function as long as possible. Weaning strategies in regard to CNI and steroids are tested. Sirolimus, everolimus, CTLA‐4 Ig, etc, are agents known to be either both nonnephrotoxic and nondiabetogenic or less so when compared with CNI. Their impact on pancreas transplantation is beginning to be evaluated. Large randomized trials in all pancreas categories, with long‐term clinical and histologic results, are mandatory to establish new guidelines for immunosuppressive regimens for pancreas transplantation.

A new technique for total hepatectomy in the pig for testing liver support devices

BACKGROUND A large animal model of total hepatectomy is suitable to test the efficacy of any system designed to support patients in hepatic coma. The models previously described in the pig entail a significant degree of surgical trauma, which might alter the evolution of the ensuring hepatic failure and compromise the reproducibility of the model. METHODS Twenty-eight pigs underwent a total hepatectomy according to a new technique. A model was considered satisfactory when it required no blood transfusions and when hematologic and hemodynamic parameters determined before, during, and until 4 hours after hepatectomy showed no significant variations. Moreover, to revive the pattern of hepatic coma produced in the anhepatic model, 7 pigs were monitored until brain death occurred. RESULTS Twenty-five pigs (89%) underwent a smooth total hepatectomy with minimal variations of the selected parameters. They constituted a highly homogeneous group. Survival of the 7 pigs, followed up until brain death occurred, ranged from 625 to 1595 minutes (mean 1013.57 minutes). The animals remained stable until a few hours before brain death, an event heralded by a final sharp increase of the serum ammonia level and by a well-evident decline of both arterial pressure and liver-dependent clotting factors. CONCLUSIONS This technique of total hepatectomy allows the construction of a reproducible model of anhepaty suitable to test the efficacy of any system conceived to temporarily replace hepatic functions.