Ennio La Rocca

Improvement of glucose/insulin metabolism reduces hypertension in insulin-dependent diabetes melitis recipients of kidney-pancreas transplantation

There is increasing evidence that metabolic disorders are common in patients with hypertension. To evaluate the relationship between glucose/insulin metabolism and hypertension in diabetes, 61 hypertensive uremic insulin-dependent diabetes mellitus patients who were recipients of kidney or pancreas/kidney transplants were studied through a 1-year follow-up. Twenty of them received a kidney (K) transplant alone, 13 received a kidney and segmental pancreas (KSP), and 28 received a kidney and whole pancreas (KWP) with duodenocystostomy. All subjects received the same immunosuppressive treatment including steroids, azathioprine, and cyclosporine. The three groups of patients were comparable for biochemical parameters, clinical characteristic, cyclosporine levels, and renal function (creatinine < 2 mg/dl). The association between hypertension and type of transplant was evaluated according a global chi-square test, then the results were broken down into two components to test for differences in hypertension between KP versus K and KWP versus KSP groups. The improvement of hypertension rate was statistically associated with KP transplant the first week after surgery, at discharge, and 1 year after transplantation (hypertension% at 1 week: KWP = 75, KSP = 23 vs. K = 70, P = 0.004; at discharge: KWP = 39, KSP = 31 vs. K = 75, P = 0.017; at 1 yr: KWP = 44, KSP = 54 vs. K = 85, P = 0.02). One year after graft fasting, free immunoreactive insulin as well as glycosylated hemoglobin and glucose levels were statistically lower in the KP groups than in the K-alone recipients. The improvement of hypertension observed in KP recipients suggests a key role of glucose and insulin metabolism on pathogenesis of diabetic hypertension.

Novel therapeutic approaches for diabetic nephropathy and retinopathy.

Diabetes mellitus is a chronic disease that in the long-term increases the microvascular and macrovascular degenerative complications thus being responsible for a large part of death associated with diabetes. During the years, while preventive care for diabetic patients has improved, the increase in the prevalence of diabetes worldwide is continuous. The detrimental effects of diabetes mellitus result in microvascular diseases, which recognize hyperglycemia as major determinant. A significant number of potential therapeutic targets for the treatment of diabetic microvascular complications have been proposed, but the encouraging results obtained in preclinical studies, have largely failed in clinical trials. Currently, the most successful strategy to prevent microvascular complications of diabetes is the intensive treatment of hyperglycemia or the normalization of glycometabolic control achieved with pancreatic and islet transplantation. In this review, we focus on the novel therapeutic targets to prevent the development and progression of diabetic nephropathy and retinopathy microvascular complications.

Outcome of pregnancy after organ transplantation: a retrospective survey in Italy

The number of women who decide to have a child after organ transplantation has increased. We determined the outcomes of 67 pregnancies of women who had undergone kidney, liver or heart transplantation. All recipients had been maintained on immunosuppressive therapy before and during pregnancy. Pregnancy complications at term were observed in 17 out of 67 women (25%), hypertension being the most frequent complication (16.17%). Two transplant rejections were reported. Sixty-eight infants were delivered (including one pair of twins); five women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born at term and 28 (41.2%) before term. The babies were followed-up for 2 months to 13 years. According to our previous experience, our study shows that patients who have undergone organ transplantation can give birth to healthy infants as long as they are monitored accurately during pregnancy.

Segmental Duct-Obstructed Pancreas Grafts Versus Pancreaticoduodenal Grafts With Enteric Diversion

Between January 1985 and September 1987, we performed a prospective comparative study between segmental-pancreas transplantation with duct obstruction by neoprene (n = 17) and pancreaticoduodenal transplantation with enteric diversion to a Roux-en-Y intestinal loop (n = 14). All recipients had insulin-dependent diabetes. The immunosuppressive protocol consisted of low doses of the steroids cyclosporin A and azathioprine. Mean follow-up was 16.5 mo for the enteric-diversion group and 13.5 mo for duct-obstructed groups. Two-year patient and pancreas- and kidney-graft actuarial survival rates were 92.9, 75.5, and 74.2%, respectively, in the former group and 92.3, 58.4, and 63.7%, respectively, in the latter group (NS). Five whole-organ grafts were lost (3 vascular thromboses, 1 pancreatitis, 1 rejection), and four segmental grafts were lost (2 vascular thromboses, 1 bleeding, 1 patients death with functional graft). More surgical complications occurred in the recipients of whole-organ grafts and were often related to the intestinal anastomosis. A satisfactory blood glucose control was observed at 3 mo and 1 yr in both groups. Provocative tests showed higher and prompter insulin secretion in patients with wholeorgan grafts. In patients with segmental grafts, the response was lower and delayed with a general tendency to impaired glucose tolerance. A marked hyperinsulinemia after meals was observed in whole-organ graft recipients. Slight nocturnal hyperinsulinemia was observed in both groups. At 1 yr, glycosylated hemoglobin was normal in both groups. The absence of a significant difference between the two groups, in terms of survival and graft function, and the lower surgical complication rate seen with segmental grafts have made us return to neo p re ne-injected segmental grafts.

Lipoprotein profile after combined kidney-pancreas transplantation in insulin-dependent diabetes mellitus

In order to evaluate the effect of a combined kidney-pancreas (KP) transplantation in insulin-dependent diabetes mellitus (IDDM) patients on the lipid and lipoprotein profile, 15 KP patients were compared with 11 kidney (K)-transplanted IDDM patients, 19 IDDM patients on hemodialysis (HD), and 15 nondiabetic control subjects. Cholesterol, triglycerides, apo AI, and apo B were measured in total plasma and in VLDL, LDL, and HDL of all participants. VLDL-cholesterol, VLDL-triglycerides, and VLDL-apo B were significantly lower in KP patients, but not in K patients, than in HD patients. In addition, patients in the K, but not in the KP, group showed high levels of apo B in LDL and an increased triglyceride/apo B ratio in VLDL, compared with patients in the HD group. The percentage of apo AI associated with HDL was significantly higher in both transplanted groups than in the HD group. However, compared with a nondiabetic control population, an increase in VLDL particles and in triglyceride content in LDL and HDL still persisted following combined KP transplantation. Insulin resistance (probably due to steroid therapy) associated with high peripheral and potentially low hepatic insulin levels (due to the systemic drainage of the transplanted pancreas) could be the main causes of the remaining lipoprotein abnormalities.

Self-Expandable Metal Stent Placement for Closure of a Leak after Total Gastrectomy for Gastric Cancer: Report on Three Cases and Review of the Literature

In the setting of the curative oncological surgery, the gastric surgery is exposed to complicated upper gastrointestinal leaks, and consequently the management of this problem has become more critically focused than was previously possible. We report here three cases of placement of a partially silicone-coated SEMS (Evolution Controlled Release Esophageal Stent System, Cook Medical, Winston-Salem, NC, USA) in patients who underwent total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy for a gastric adenocarcinoma. The promising results of our report, despite the small number of patients, suggest that early stenting (through a partially silicone-coated SEMS) is a feasible alternative to surgical treatment in this subset of patients. In fact, in the treatment of leakage after total gastrectomy, plastic stents and totally covered metallic stents may not adhere sufficiently to the esophagojejunal walls and, as a result, migrate beyond the anastomosis. However, prospective studies with a larger number of patients might assess the real effectiveness and safety of this procedure.

Could JC virus provoke metastasis in colon cancer

AIM To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ(2) test. RESULTS Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ(2) = 9.55, P = 0.002). CONCLUSION JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.

Impact of immunosuppression on improvement of results in clinical pancreas transplantation.

Since November 1975, 103 pancreas transplantations have been performed in 97 insulin-dependent diabetic patients. Pancreas and kidney were grafted simultaneously in 84 patients (plus 1 double retransplantation). Eighty-nine pancreas grafts were prepared by duct obstruction with neoprene, and 14 were pancreaticoduodenal grafts with enteric diversion in a Roux-en-Y loop. Five immunosuppressive protocols were subsequently used. With the latest protocols, patient and pancreas survival improved to 93 and 72% at 1 yr, respectively. The improvement in graft survival appeared to be particularly related to the reduction of the number of pancreas grafts lost in rejection. The patients treated with the last protocols, including cyclosporin A (CsA) and only low doses of steroids, showed a better glucose tolerance after provocative tests. Pancreas-graft function did not appear to be influenced by CsA treatment.

Indications for pancreas transplantation

The main currently accepted indication for pancreas transplantation is type 1 diabetes with accompanying kidney transplantation for end-stage renal failure. The pancreas transplants mostly have been performed simultaneously with or after the kidney transplants, although in qualified surgical centers, pancreas transplants alone have been frequently performed. Furthermore, cases of a combined kidney and segmental pancreas transplant from a living donor also exist. Today, kidney–pancreas transplantation must be proposed to prolong patient survival and to improve quality of life and decrease secondary complications from diabetes. In view of the recently achieved results in terms of cardiac function and autonomic neuropathy, pancreas transplantation could be offered in nonselected patients who are prone to congestive heart failure. Pancreas transplantation alone should be considered a therapy for nonuremic patients with brittle diabetes, associated with clinical and emotional problems with exogenous insulin therapy, which are so severe as to be incapacitating.

Lipoprotein profile after combined kidneypancreas transplantation in insulindependent diabetes mellitus

Abstract In order to evaluate the effect of a combined kidney‐pancreas (KP) transplantation in insulin‐dependent diabetes mellitus (IDDM) patients on the lipid and lipoprotein profile, 15 KP patients were compared with 11 kidney (K)‐transplanted IDDM patients, 19 IDDM patients on hemodialysis (HD), and 15 nondiabetic control subjects. Cholesterol, triglycerides, apo AI, and apo B were measured in total plasma and in VLDL, LDL, and HDL of all participants. VLDL‐cholesterol, VLDL‐triglycerides, and VLDL‐apo B were significantly lower in KP patients, but not in K patients, than in HD patients. In addition, patients in the K, but not in the KP, group showed high levels of apo B in LDL and an increased triglyceride/apo B ratio in VLDL, compared with patients in the HD group. The percentage of apo AI associated with HDL was significantly higher in both transplanted groups than in the HD group. However, compared with a nondiabetic control population, an increase in VLDL particles and in triglyceride content in LDL and HDL still persisted following combined KP transplantation. Insulin resistance (probably due to steroid therapy) associated with high peripheral and potentially low hepatic insulin levels (due to the systemic drainage of the transplanted pancreas) could be the main causes of the remaining lipoprotein abnormalities.