Donna Hathaway

Results of pancreas transplantation with portal venous and enteric drainage.

PURPOSE The 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. PROCEDURES All 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. FINDINGS Patient 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. CONCLUSIONS These 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.

Improvement in autonomic and gastric function following pancreas-kidney versus kidney-alone transplantation and the correlation with quality of life.

We conducted a series of studies to document changes in autonomic and gastrointestinal function following pancreas-kidney and kidney-alone transplantation, define how autonomic function is associated with quality of life, and identify how transplantation alters the quality of life of diabetic transplant recipients.Uremic type I diabetic patients receiving combined pancreas-kidney (n=23) or kidney-alone (n=16) transplants completed pre- and 12-month-posttransplant evaluation of vasomotor function (total capillary pulse amplitude, capillary vasoconstriction response to cold, capillary response to postural adjustments), cardiac function (R-R interval variation, valsalva ratio), overall autonomic function (total autonomic score, autonomic index), gastric function (cutaneous electroga-

A comparison of media supplement methods for the extended culture of human islet tissue

BACKGROUND The preservation of sufficient quantities of islets for human transplantation has proven to be a tenacious problem for researchers and transplant programs. Beyond the variables associated with islet procurement, there is the problem of tissue storage before transplantation. Cryopreservation has been adopted as a method for long-term islet storage that allows for recovery of viable tissue. However, there is significant tissue loss during the process and the possibility that long-term viability may be compromised. An alternate method of prolonged culture at 24 degrees C was initially introduced as a means of reducing islet antigenicity. Although successful in the short term, prolonged culture with serum-based media has also resulted in a significant loss of tissue. In this study, we report the successful use of an ITS+ Premix-supplemented serum-free media for prolonged islet culture and its comparison to fetal bovine serum-supplemented media and to cryopreservation. METHODS Pancreata were procured from cadaveric organ donors, and islets were isolated using our own modification of the automated method of Ricordi. Aliquots from a series of human islet isolations were cultured in parallel in (A) CMRL + ITS (serum-free media; SFM) or (B) CMRL +10% fetal bovine serum (standard media) and compared with cryopreserved and thawed tissue. RESULTS Our results show that SFM allows for the long-term culture of islet tissue. For time points up to 2 months, islets cultured in SFM showed recovery ratios greater than those for standard serum-supple. mented media. At 1 week and 1 month, islet recovery ratios were greater for SFM-cultured islets than for cryopreserved tissue. Viability studies confirmed that the SFM-cultured islets were able to respond to glucose stimulation (stimulation index 0.8-21.2). Additionally, in vivo results using cultured islets in a patient demonstrated good islet function, with a 1-month stimulation index of 4.02 in response to an intravenous glucose tolerance test. CONCLUSION We conclude that this culture modification represents a method by which functional islet tissue can be maintained in long-term culture and successfully transplanted.

Choice of surgical technique influences perioperative outcomes in liver transplantation.

OBJECTIVE To examine how the choice of surgical technique influenced perioperative outcomes in liver transplantation. SUMMARY BACKGROUND DATA The standard technique of orthotopic liver transplantation with venovenous bypass (VVB) is commonly used to facilitate hemodynamic stability. However, this traditional procedure is associated with unique complications that can be avoided by using the technique of liver resection without caval excision (the piggyback technique). METHODS A prospective comparison of the two procedures was conducted in 90 patients (34 piggyback and 56 with VVB) during a 2.5-year period. Although both groups had similar donor and recipient demographic characteristics, posttransplant outcomes were significantly better for the patients undergoing the piggyback technique. The effect of surgical technique was examined using a stepwise approach that considered its impact on two levels of perioperative and postoperative events. RESULTS The analysis of the first level of perioperative events found that the piggyback procedure resulted in a 50% decrease in the duration of the anhepatic phase. The analysis of the second level of perioperative events found a significant relation between the anhepatic phase and the duration of surgery and between the anhepatic phase and the need for blood replacement. The analysis of the first level of postoperative events found that the intensive care unit stay was significantly related to both the duration of surgery and the need for blood replacement. The intensive care unit stay was in turn related to the second level of postoperative events, namely the length of hospital stay. Finally, total charges were directly related to length of hospital stay. The overall 1-year actuarial patient and graft survival rates were 94% in the piggyback and 96% in the VVB groups, respectively. CONCLUSIONS These data demonstrate that surgical choices in complex procedures such as orthotopic liver transplantation trigger a chain of events that can significantly affect resource utilization. In the current healthcare climate, examination of the sequence of events that follow a specific treatment may provide a more complete framework for choosing between treatment alternatives.

Kidney-pancreas transplantation: The effect of portal versus systemic venous drainage of the pancreas on the lipoprotein composition

We have previously shown that both kidney-alone and combined kidney-pancreas transplantation lower VLDL and IDL apoB while increasing LDL apoB, apoA-I, and HDL free cholesterol (FC). In this report, we analyze the lipoproteins of 31 patients who have undergone combined kidney-pancreas transplantation. Systemic venous drainage of the pancreas was utilized in 20 of these patients while 11 had portal venous drainage. Six lipoprotein subfractions (VLDL, IDL, LDL, HDL-L, HDL-M, HDL-D) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase HPLC) and lipid (by enzymatic assays) composition of each subfraction was determined. After three months, there were few group differences. However, the portal group had substantial reductions in VLDL apoB at both six (-50% vs. +1%) and twelve months (-57% vs. +149%, P = .042) while the systemic group had increases in VLDL apoB. Similar differences were seen in IDL apoB (six months: -38% vs. +13%; twelve months: -61% vs. +56%, P = .008). LDL apoB increased in both groups at six months (portal: +7%; systemic: +30%) but fell in the portal group at twelve months (-17% vs. +41%, P = .0007). IDL triglyceride, cholesterol ester, phospholipids, and free cholesterol also fell by 19% to 47% in the portal group while they rose by 8% to 44% in the systemic patients, six and twelve months after surgery (P < .05). In addition, the VLDL and LDL free cholesterol to phospholipid ratios (FC/PL) fell (improved) by 16% to 26% in the portal patients while they rose by 9% to 28% in the systemic subjects during this time (P < .04). Finally, there were substantial improvements in the LDL composition of the portal patients compared to the systemic patients at six (PL/apoB: +23% vs. -16%, P = .005; CE/apoB: +14% vs. -14%, P = .037) and twelve months (PL/apoB: +39% vs. -13%, P = .011; CE/apoB: +41% vs. -15%, P = .011). These data indicate that portal drainage of the transplanted pancreas reduced the number of VLDL, IDL, and LDL particles, reduced the total mass of IDL (by 35%), and normalized the VLDL and LDL particle composition. These improvements were not seen in the patients who received systemic drainage of their pancreas. HDL-M also improved in the portal patients (TG: -29% vs. +12%, P = .025) (PL: +22% vs. -5%, P = .014) (total mass: +16% vs. +0.2%, P = .044) but not in the systemic patients six months after surgery. These results suggest that portal venous drainage of the pancreas leads to greater improvements in the lipoprotein composition of IDDM patients than does systemic drainage.

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.

The first report from the patient outcomes registry for transplant effects on life (PORTEL): differences in side-effects and quality of life by organ type, time since transplant and immunosuppressive regimens.

Abstract: Background:  Post‐transplant patient quality of life (QOL) is affected by a number of different factors. A nationwide patient registry has been established to evaluate QOL and determine the effects of transplant and immunosuppressive regimens on patient outcomes.

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.

Evolution in pancreas transplantation techniques: simultaneous kidney-pancreas transplantation using portal-enteric drainage without antilymphocyte induction.

OBJECTIVE To report initial experience with the combination of a novel technique of portal-enteric pancreas transplantation with newer immunosuppressive strategies that eliminate antilymphocyte induction therapy. BACKGROUND A new surgical technique of pancreas transplantation has been developed with portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric). The introduction of potent immunosuppressive agents may allow simultaneous kidney and pancreas transplants (SKPT) to be performed without antilymphocyte induction. METHODS From September 1996 to November 1998, the authors performed 28 primary SKPTs with portal-enteric drainage and no antilymphocyte induction. All patients received triple immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. The study group had a mean age of 38 years and a mean preoperative duration of diabetes of 25 years. Four patients (14%) had prior kidney transplants. RESULTS All patients had immediate renal allograft function. Actual patient, kidney, and pancreas graft survival rates were 86%, 82%, and 82%, respectively, after a mean follow-up of 12 months. Four patients died, three as a result of cardiac events unrelated to SKPT. Five kidney and five pancreas grafts were lost, including five deaths with function and three cases of chronic rejection. The mean length of stay and total charges for the initial hospital stay were 12.5 days and

Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant.

99,517. The mean number of readmissions was 2.9, and 10 patients (36%) had no readmissions. Six patients (21 %) developed acute rejection, with five (18%) receiving antilymphocyte therapy. Seven patients (25%) underwent relaparotomy, including two (7%) for intraabdominal infection. Nine patients (32%) had major infections, including three (11%) with cytomegaloviral infection. Of the 24 surviving patients, 22 (92%) are both dialysis- and insulin-free. CONCLUSION These preliminary results suggest that SKPT with portal-enteric drainage without antilymphocyte induction can be performed with excellent outcomes.