C. Staudacher

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

SummaryTo evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry. Nine of the original 15 patients were studied again after four months and six after 12 months, successful combined kidney-pancreas transplantation with the same experimental protocol. Nine volunteers formed the group of normal subjects. Combined kidney-pancreas transplantation normalised hepatic glucose production and reduced peripheral insulin resistance in Type 1 diabetic uraemic patients, despite chronic immunosuppressive therapy. To further evaluate the hypothesis that residual insulin resistance was due to chronic steroid therapy, 11 additional subjects with chronic uveitis (six of whom were treated with only prednisone, and five treated only with cyclosporin) underwent the same protocol demonstrating a normal hepatic glucose production. The insulin-stimulated peripheral glucose uptake was reduced in the prednisone-treated group, but normal in cyclosporin-treated subjects. Four additional diabetic patients with a kidney transplant were also studied. They showed a peripheral insulin sensitivity intermediate between diabetic uraemic patients and patients after combined transplant. We conclude that short-term (one year) combined kidney-pancreas transplantation improves glucose metabolism by restoring normal rates of hepatic glucose production and reducing peripheral insulin resistance; chronic steroid therapy is the major determinant of residual reduced insulin action. Both kidney and pancreas substitution play a role in reducing peripheral insulin resistance.

Lack of Feedback Inhibition of Insulin Secretion in Denervated Human Pancreas

In this study, pancreas transplantation is used as a clinical model of pancreas denervation in humans. To assess the role of innervation on the feedback autoinhibition of insulin secretion, we studied four groups of subjects--group 1: 16 patients with combined pancreas and kidney transplantation (plasma glucose = 5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The following means were used to study the groups: 1) a two-step hyperinsulinemic euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3 mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2, 3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/- 0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4, respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45, 20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Sclerotherapy plus octreotide versus sclerotherapy alone in the prevention of early rebleeding from esophageal varices: A randomized, double-blind, placebo-controlled, multicenter trial

Because of its ability to decrease portal pressure, azygos blood flow, and postprandial splanchnic hyperemia, octreotide administration could be effective in reducing early rebleeding in patients undergoing endoscopic variceal sclerotherapy (EVS). We report the results of a trial comparing EVS + octreotide versus EVS alone. Consecutive patients with cirrhosis and endoscopically proven variceal hemorrhage were considered eligible for the trial if hemodynamically stable for at least 24 hours after bleeding stopped. Patients with advanced liver cancer or having received EVS treatment in the past were not enrolled. After enrollment patients were submitted to EVS (day 1); all patients were randomized to receive octreotide, 100 μg three times a day subcutaneously, or an identical placebo, up to day 29; EVS was repeated at days 8, 15, and 29. Fifty‐eight patients were randomized to receive either EVS + octreotide (n = 26) or EVS alone (n = 32). The two groups were evenly balanced for sex, age, Child‐Pugh class, history of previous bleeding, endoscopic appearance of varices, or treatment received in emergency. Eight of 26 (31%) patients in the EVS + octreotide group rebled, compared with 11 of 32 (34%) in the EVS group. Four of the eight (50%) patients in the former group and 8 of 11 (73%) in the latter, respectively, bled within day 15. There were 10 (38.5%) deaths in the EVS + octreotide group (seven bleeding‐related), compared with seven (21.9%) (five bleeding‐related) in the EVS group; these differences did not reach statistical significance. Administration of octreotide, 100 μg three times a day, subcutaneously, to patients undergoing EVS for prevention of recurrent variceal bleeding does not decrease the incidence of early rebleeding.

Laparoscopic assisted duodenopancreatectomy

BackgroundIn the past few years, minimally invasive therapy for pancreatic diseases has made significant strides but the role of laparoscopic pancreaticoduodenectomy is still controversial.MethodsFour patients with a mean age of 44 ± 11 years were chosen for a laparoscopic pancreaticoduodenectomy. Pathological diagnoses were ductal adenocarcinoma in one, neuroendocrine tumor in two, and metastatic malignant melanoma in one.ResultsThe procedure was laparoscopically completed in all with a mean operating time, blood loss, and hospital stay of 416 ± 77 min, 325 ± 50 ml, and 12 ± 2 days, respectively. There were no complications attributable to this surgery and there were no deaths. The average number of dissected lymph nodes was 26 ± 17 (range 16-47). All the patients remained well at a median follow-up of 4.5 months (range 1-10).ConclusionsIt can be inferred from this small but successful experience that laparoscopic pancreaticoduodenectomy can be considered for the treatment of tumors of the pancreas or periampullary region.

Laparoscopic treatment of advanced colonic cancer: a case-matched control with open surgery.

The safety, feasibility and oncological results of laparoscopic resection for advanced colon cancer were evaluated.

Impact of previous abdominal surgery on the outcome of laparoscopic colectomy: a case-matched control study

BackgroundAdhesions are a major risk for visceral injury and can increase the difficulty of both laparoscopic and open colectomy. The aim of the present study was to evaluate the impact of previous abdominal surgery on laparoscopic colectomy in terms of early outcome.MethodsWe performed a case-control study of patients who underwent laparoscopic colectomy for colorectal disease. The case group comprised 91 patients with a history of prior abdominal surgery, while the 91 controls had no such history. Case and controls were matched for age, gender, site of primary disease, comorbidity on admission and body mass index.ResultsThe two groups were homogeneous for demographic and clinical characteristics. Conversion rate was 16.5% in the case group and 8.8% in the control group (p=0.18). Of the 7 patients who underwent conversion because of adhesions, six had prior surgery (cases) and one did not (p=0.001). Operative time was 26 minutes longer in the case group than in the control group (p=0.001). Morbidity rate was 25.3% among cases and 23.1% for controls. Patients in the two groups experienced a similar time to recovery of bowel function, length of postoperative stay, and 30-day readmission rate.ConclusionsLaparoscopic colectomy in previously operated patients is a time-consuming operation, but it does not appear to affect the short-term postoperative outcome.

Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: a phase I and II trial.

Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status ≥ 60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade ≥ 3 nonhematological toxicity, or failure to recover to grade ≤ 1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

Effect of pancreas transplantation on life expectancy, kidney function and quality of life in uraemic Type 1 (insulin-dependent) diabetic patients

SummaryThe aim of our study was to evaluate the effects of haemodialysis, kidney transplantation and simultaneous kidney and pancreas transplantation on survival of diabetic subjects and on kidney function. 40 Type 1 (insulin-dependent) diabetic patients received a kidney transplantation: in 31 cases the kidney was transplanted simultaneously to a pancreas graft from the same donor (KP group), while in 9 cases the pancreas was not available (K group). 44 uraemic Type 1(insulin-dependent) diabetic patients on dialysis and in waiting list for kidney transplantation, constituted the control group (HD group). Patient survival rate 1, 3 and 5 years following transplantation was better in KP group (93%, 89%, 89%, respectively) than in K group (88%, 88%, 73%, respectively) and in HD group (88%, 62%, 51%, respectively). Kidney graft survival at 1, 3 and 5 years post-transplant was better in KP group (93%, 72%, 72%, respectively) than in K group (76%, 61%, 31%, respectively). 1 year after transplantation, patients of the KP group who had lost the pancreas for technical reasons (thrombosis) were included in the K group so as to evaluate the effect of the transplanted pancreas on long-term patient and kidney survival. Patient survival rate in the KP group (17 patients) at 2 and 4 years was 100%, while at the same intervals it was 78% in the K group (13 patients). Kidney graft function rate at 2 and 4 years was 93% in the KP group (17 grafts) and 54% and 27% respectively in the K group (14 grafts). Evaluation of quality of life in patients receiving a kidney and pancreas transplantation showed an improvement in psychological well-being, when compared to patients receiving a kidney transplantation alone. Physical well-being was similar in patients transplanted with kidney and pancreas or with kidney alone.

The role of cardiovascular hemodynamics and liver histology in evaluating bleeding cirrhotic patients.

Preoperative cardiovascular hemodynamics and percutaneous liver biopsies were used to evaluate the pathophysiologic factors determining the operative prognosis of patients with cirrhotic liver disease and bleeding esophageal varices. These studies confirm the observations of Siegel that the greater the magnitude of the peripheral abnormalities in vascular tone and oxygen consumption the better must be the capability of the ventricular function, if the cirrhotic is to survive emergency or urgent portal decompressive surgery. These studies also show that the cardiovascular hemodynamics are directly correllated with the nature and degree of the abnormalities in the liver biopsy, and that pathologic and physiologic features of this disease which impact on surgical prognosis can be expressed through the easily obtained Survival Index. Bleeding cirrhotic patients with poor quality hemodynamics and poor histologie characteristics should be treated non operatively, since the operative mortality appears greater than that produced by a strategy of medical supportive therapy and delayed surgery if stabilization occurs.

Dose-Intense PEFG (Cisplatin, Epirubicin, 5-Fluorouracil, Gemcitabine) in Advanced Pancreatic Adenocarcinoma: A Dose-Finding Study

The aim of this study was to assess the maximum tolerated dose (MTD) of an intensified PEFG regimen administered every 14 days to patients with Stage III or metastatic pancreatic adenocarcinoma. Twenty-nine patients received fixed doses of both epirubicin (30 mg/m2) and 5-fluorouracil (200 mg/m2/day on Days 1–14) and of escalating doses of cisplatin and gemcitabine. The MTD was cisplatin 30 mg/m2 and gemcitabine 800 mg/m2. With respect to classical PEFG, intensified regimen potentially improved the dose-intensity of both cisplatin and epirubicin by 50 percent and of gemcitabine by 33 percent, reduced Grade 3–4 haematological toxicity and the number of outpatient accesses.