Gaber Ao

Results of pancreas transplantation with portal venous and enteric drainage.

PURPOSEnThe standard method for pancreatic transplantation involves drainage of exocrine secretions into the urinary bladder with venous outflow into the systemic circulation. Despite the high success rate associated with this approach, it often leads to complications, including chemical cystitis, reflux pancreatitis, metabolic acidosis, and hyperinsulinemia. The authors developed a new technique of pancreatic transplantation with portal drainage of endocrine secretions and enteric drainage of exocrine secretions (PE), which theoretically should be more physiologic.nnnPROCEDURESnAll patients were insulin-dependent diabetics with end-stage renal disease who underwent combined kidney-pancreas transplantation. Between 1990 and 1994, 19 patients have been transplanted using intraperitoneal placement of the pancreas allograft with exocrine drainage into a Roux-en Y loop and venous drainage into the portal circulations (PE). A comparison group of all patients undergoing standard systemic-bladder (SB) transplantation between April 1989 and March 1993 (n = 28) also was studied. Patient follow-up ranges from 6 months to 5 years for the SB patients (mean = 2.5 years) and 6 months to 4 years for the PE patients (mean = 1.6 years). Routine follow-up includes documentation of the clinical course and detailed endocrine studies.nnnFINDINGSnPatient and graft actuarial survival at 1 and 3 years is no different for SB and PE patients. Urinary tract infections occurred in 89.3% of the SB patients (2.8/patient) versus 26.3% of the PE patients (0.25/patient, p < or = 0.0001). None of the PE patients experienced hematuria compared with 53.6% of the SB patients (p < or = 0.0001); however, two PE patients had melanotic episodes. The incidence of urinary retention and reflux pancreatitis was 32.1% versus 5.3% (p < or = 0.028) for SB and PE groups, respectively. Patients in the SB group required sodium bicarbonate therapy (mean = 55 mEq/day) although no PE patient required routine therapy; despite this, SB patients experienced more episodes of acidosis (44 vs. 5). Endocrine studies indicate no difference in glycosylated hemoglobin or fasting and stimulated glucose values throughout the follow-up period. In contrast, hyperinsulinemia was evident in both fasting and stimulated tests for the SB patients, with values consistently two- to fivefold higher than those of the PE group.nnnCONCLUSIONSnThese results indicate that PE and SB pancreas transplantation are equivalent in terms of patient and graft survival and suggest that the PE approach is associated with a decreased incidence of metabolic and bladder-related complications. In addition, the PE approach eliminates the state of peripheral hyperinsulinemia that characterizes the SB procedure. Continued follow-up will be necessary to determine if long-term outcomes will differ for patients with PE and SB grafts.

Risk factors for postimplantation pancreatitis and pancreatic thrombosis in pancreas transplant recipients.

Reperfusion pancreatitis and pancreatic thrombosis are 2 complications of pancreatic transplantation that are associated with both an increased patient morbidity and a decrease in pancreas graft survival rates. These complications are thought to be related to donor factors, procurement and preservation variables, and postimplantation recipient management. We reviewed our experience with 41 consecutive pancreas transplant patients (18 females, 23 males) performed in association with kidney transplants (n = 34), whole (n = 5) and segmental (n = 2). The average cold ischemia time (CIT) was 11.5 hr. Donor and recipient variables were related to two outcomes: (1) postoperative pancreatitis (n = 9) and (2) postoperative pancreatic thrombosis (n = 6). Steroid administration to the donor resulted in significant reduction of postimplantation pancreatitis (P < 0.001). Also, postoperative pancreatitis was significantly less common (P < 0.02) in recipients given calcium channel blockers in the early postoperative period. Pancreatic thrombosis was significantly more common in male recipients (P < 0.04) and was also significantly related to CIT (P < 0.05). These data indicate that proper donor management and pretreatment with high-dose steroids, together with shortening of CIT and postoperative administration of calcium channel blockers, are protective against pancreatic thrombosis and pancreatitis.

OKT3 treatment of steroid-resistant renal allograft rejection.

The monoclonal antibody, Orthoclone OKT3 (OKT3), has been used with great efficacy in a prospective multicenter trial as therapy for first rejection episodes in cadaveric donor (CD) renal allograft recipients treated with azathioprine (AZA) and prednisone (P). However, although almost all rejection episodes were reversed, recurrent rejection occurred in approximately two-thirds of OKT3-treated patients in this earlier trial; infections also occurred in about two-thirds of patients, often related to the additional immunosuppression necessary to reverse the rerejection episodes. In the current series of patients, OKT3 was used to treat rejection in CD renal graft recipients in a protocol differing from the multicenter trial in two respects: (1) baseline immunosuppression was cyclosporine (CsA) and P or CsA, AZA, and P (probably more potent immunosuppressive combinations than the AZA and P in the multicenter trial); and (2) OKT3 treatment was reserved for rejection episodes resistant to 3 bolus infusions of methyl-prednisolone (MP), 5–10 mg/kg, rather than as primary therapy for first rejection episodes. Using this protocol, 46 of 74 rejection episodes (62%) diagnosed between 3/85 and 3/86 in CD renal allograft recipients were treated successfully with MP. Of the remaining 28 steroid-resistant rejection episodes, 27 (96%) were reversed with a 7–14-day course of OKT3, 5 mg/day. Only 5 recurrent rejection episodes (19%) have been observed in the 2–14-month follow-up period after OKT3 treatment; infections have occurred in 10 patients (36%), and three grafts (11%) have been lost in OKT3 treated patients. These results suggest that recurrent rejection and subsequent infection after OKT3 is used to treat rejection may be reduced in a protocol where CD renal allograft recipients are treated with baseline immunosuppression regimens including CsA and where OKT3 is reserved for steroid-resistant rejection. This approach appears to be both more cost-effective than, and as effective therapeutically as, treating all first rejection episodes with the monoclonal antibody.

Early improvement in cardiac function occurs for pancreas-kidney but not diabetic kidney-alone transplant recipients

Noninvasive M mode echocardiography with Doppler recording was prospectively performed on type I diabetic recipients of pancreas-kidney (n=20), pancreas-after-kidney (n=2), and kidney-alone (n = 11) allografts to determine whether the return of euglycemia by pancreas transplantation in the uremic diabetic person was associated with improved cardiac function. Each patient was studied preoperatively and at 6 and 12 months posttransplant. Echocardiographic parameters which were compared included measures of systolic function (shortening fraction), diastolic function (early/active peak velocity ratio, early/active integral ratio), and left ventricular geometric parameters (interventricular septal thickness, posterior wall thickness, left ventricular mass). The only statistically significant improvement observed for kidney-alone recipients was an increased shortening fraction from baseline (24.91%) to 6 months (32.13%, P ≤ 0.0188). In contrast, the pancreas group demonstrated sustained improvement in all outcomes with measures at 12 months consistently showing a significant improvement from baseline which was also significantly better than that reported for the kidney-alone group. This study showed stabilization of cardiac function by echocardiography for diabetic kidney-alone recipients, whereas significant improvement in function occurred for pancreas-kidney recipients. The improvement in cardiac function for pancreas recipients was seen at 6 months with continued improvement evident at 12 months.

Changes in Gastric Emptying in Recipients of Successful Combined Pancreas-Kidney Transplants

Gastroparesis causes gastric emptying disorders in patients with chronic diabetes mellitus and it results from reduced smooth muscle contractility secondary to autonomic dysfunction. Today there has been little objective evidence of improvement in gastric emptying following correction of both uremia and diabetes by combined kidney-pancreas transplantation. We used gastrointestinal symptom scores, solid gastric emptying tests and electrogastrography to evaluate the effect of combined kidney-pancreas transplantation on gastric emptying in 8 uremic diabetic patients. The mean age of the patients was 40 years (range: 30-51 years) and the mean duration of diabetes was 24 years (range: 16-30 years). The patients had been on dialysis up to 24 months. The pretransplant A1 mean was 6.5 before improving to 4.3 after transplantation. All patients were receiving exogenous insulin. Our study data indicate that uremic diabetics have a high prevalence of symptomatic gastrointestinal dysfunction including abnormalities of gastric emptying and gastric electrical activity. Following transplantation, the gastrointestinal symptomatology improved significantly. Significant improvement in the rate of gastric emptying also correlated with improvement in the symptom complex. Gastric electrical activity also improved during the follow-up period.

Calcium Channel Blockade Inhibits Release of TNFα and Improves Survival in a Rat Model of Acute Pancreatitis

Tumor necrosis factor-α (TNFα) has been implicated as one of the numerous likely mediators of the systemic complications of acute pancreatitis. Recent suggestions that calcium (Ca2+) acts as a signal not only for TNFα release but also for TNFα action at distant sites led us to hypothesize that the calcium channel blocker diltiazem could inhibit TNFα release in acute pancreatitis, ameliorating the severity of the disease and improving overall survival. A rat model of acute pancreatitis induced by retrograde ductal infusion of bile was used for two experiments (n = 120). Experiment 1 was designed to determine the effects of calcium channel blockade using diltiazem on the severity of pancreatitis as measured by changes in biochemistry, pathology, and serum TNFα levels. In experiment 2, effects of calcium channel blockade on animal survival were measured over 72 h. Calcium channel blockade was associated with a significant reduction in serum TNFα levels as well as amelioration of pancreatitis by biochemical and pathological criteria. Overall survival from bile-induced pancreatitis was dramatically improved in rats pretreated with diltiazem (80%) compared to untreated animals (40%). Our data suggest that calcium channel blockade is associated with TNFα inhibition and improved outcome in a rat model of acute pancreatitis.

Serial analysis of biomarkers of acute pancreas allograft rejection

Cashion AK, Sabek O, Driscoll C, Gaber L, Tolley E, Gaber AO. Serial analysis of biomarkers of acute pancreas allograft rejection. u2028Clin Transplant 2010: 24: E214–E222.