Bladder Drainage Of Exocrine Secretions Research Articles

Evolution of Pancreas Transplantation At A Single Institution-50+ Years and 2500 Transplants.

To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades. The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era. All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year death-censored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

Exocrine drainage of the transplanted pancreas: A review

Pancreas transplant is an important treatment option for insulin dependent diabetic patients as it may result in physiologic euglycemia. Improvements in surgical technique, graft preservation, immunosuppression, diagnosis and management of rejection, and management of post-transplant complications have led to improved patient survival.There are several technical variables to consider when performing a pancreas transplant. One is the type of exocrine drainage to be used. The most common types of exocrine drainage are enteric or bladder drainage. Gastric- exocrine drainage has also been recently introduced. The most commonly cited complications associated with bladder drainage include metabolic complications, urologic complications and the need for enteric conversion.Many complications related to bladder drainage can be managed non-operatively with Foley catheter drainage. For those complications that cannot be managed in this manner, enteric conversion is an option. Complications associated with enteric drainage include anastomotic leak and intra-abdominal abscess, although at rates lower than cited in the early literature on the topic. Bladder drainage of exocrine secretions and enteric drainage of exocrine secretions, or a staged procedure with bladder drainage followed by indicated or elective enteric conversion are reasonable options for drainage of the exocrine secretions of the pancreas. Gastric-exocrine drainage is a promising therapy deserving of future exploration.

Bladder vs enteric drainage following pancreatic transplantation: How best to support graft survival? A best evidence topic

A best evidence topic in transplant surgery was written according to a structured protocol. The question addressed was: In patients undergoing pancreatic transplantation alone, does enteric drainage or bladder drainage of exocrine secretions provide the best graft survival?A total of 155 papers were identified using the search protocol described, of which four retrospective cohort studies represented the best evidence available to answer the clinical question. The authors, journal, date and country of publication, study type, patient group studied, relevant outcomes and results of these papers are tabulated.Three of the four studies demonstrated no significant difference in graft survival between enteric drainage and bladder drainage at 6 months or 1 year. This included the largest and most recent study which showed that patient survival, graft survival and technical failure rates at 1 year were equal between the two duct management techniques. However, one study indicated lower graft survival at 1 year with enteric drainage due to a higher technical failure rate.Therefore, the clinical bottom line is that there is no significant difference in graft survival between enteric drainage or bladder drainage of pancreatic exocrine secretions for pancreas transplants alone. There is some evidence that enteric drainage may be associated with higher technical failure and higher graft rejection but this has not been universally demonstrated. Given the historical nature of all the available evidence, further appropriately powered and randomised Level 1 studies are necessary to clarify this important issue.

A Composite Risk Model for Predicting Technical Failure in Pancreas Transplantation

Technical failure (TF) continues to have a significant impact on the success of pancreas transplantation. We assessed risk factors for TF in 1115 pancreas transplants performed at a single center between 1998 and 2011. The overall TF rate was 10.2%. In a multivariable model, donor BMI ≥30 (HR 1.87, p = 0.005), donor Cr ≥2.5 (HR 3.16, p = 0.007), donor age >50 (HR 1.73, p = 0.082) and preservation time >20 h (HR 2.17, p < 0.001) were associated with TF. Bladder drainage of exocrine secretions was protective (HR 0.54, p = 0.002). We incorporated these factors in a Composite Risk Model. In this model the presence of one risk factor did not significantly increase risk of TF (HR 1.35, p = 0.346). Two risk factors in combination increased risk greater than threefold (HR 3.65, p < 0.001) and three risk factors increased risk greater than sevenfold (HR 7.66, p = <0.001). The analysis also identified many factors that were not predictive of TF, including previous transplants, immunosuppressive agent selection, and almost all recipient demographic parameters. While the model suggests that two or more risk factors predict TF, strategies to reduce preservation time may mitigate some of this risk.

Pancreas Transplant Salvage by Proximal Loop Ileostomy and Distal Ileostotomy Tube for Duodenal Stump Leak after Enteric Conversion

After pancreas transplantation, some patients with bladder drainage (BD) of the pancreatic duct will need to be converted to enteric drainage (ED) because of reflux pancreatitis, metabolic acidosis, and urological complications. However, ED is associated with higher rates of duodenal stump leak, intra-abdominal abscess, and peritonitis. In some cases of enteric anastomosis leakage, a primary repair can be attempted, but in more severe cases, graft pancreatectomy is indicated. We report one patient who received a combined kidney and pancreas transplant with BD of exocrine secretions, but who required ED conversion 6 years later because of persistent metabolic acidosis and adverse urological symptoms. However, a significant duodenal leak was discovered 4 days post-operatively. To salvage the transplanted pancreas, we performed a diverting loop ileostomy proximal to the entero-entero anastomosis and the distal section was drained retrogradely with an ileostostomy tube, allowing the area of the leak to heal. Three months later, the ileostomy was reversed without complications, the symptoms that led to the ED conversion resolved, and the kidney and pancreas allografts remain functional 48 months later. We suggest that this might be a method by which transplanted pancreas may be salvaged in the case of leakage after ED conversion.

Initial Australasian experience with portal-enteric drainage in simultaneous pancreas-kidney transplantation

Pancreas-kidney transplantation is currently the most effective method to re-establish euglycaemia in insulin-dependent diabetics with associated renal failure. The standard technique employed has been bladder drainage of exocrine secretions coupled with systemic venous drainage ('systemic-bladder' (SB) drainage). The more physiological technique, enteric exocrine with portal venous drainage ('portal-enteric' (PE) drainage), has been utilized sparingly in the past as a result of fears of technical complications. This paper compares the Monash Medical Centre experience with both techniques. A total of 68 simultaneous pancreas-kidney transplantations were performed at Monash Medical Centre from 1991 until 2004. The first 37 received SB drainage. Since March 2001, 27 have received PE drainage. This retrospective study compared the SB group (n= 37) with the PE group (n= 27), with a 2-year follow-up, examining a number of surgical outcomes. Two-year patient (94.3 versus 96.0%), kidney (89.2 versus 85.2%), pancreas (77.9 versus 71.4%) and event-free (73.0 versus 67.7%) survivals were all similar between the SB and PE groups, respectively. Although surgery took longer in PE subjects (4 h : 47 min ± 0:48 versus 5 h : 16 min ± 1:00; P= 0.045), less intraoperative transfusions were required (1.3 ± 1.43 versus 0.52 ± 0.90; P= 0.024). Length of hospital stay and time to insulin independence were similar. Pancreas graft thrombosis rates were similar (10.8% SB versus 7.4% PE, P= 0.497). PE drainage is a safe and viable method for pancreas transplantation, which can be performed with excellent outcomes. An increased rate of complications with PE drainage has not been demonstrated in this series.

Pancreaticoduodenal transplantation with portal venous and enteric drainage in rats.

The use of combined pancreatic and renal transplantation in patients with diabetes and end-stage renal failure has gained widespread recognition as an acceptable treatment option. The prevailing method used for transplantation of the pancreas involves anastomosis of the graft’s portal vein and the recipient’s iliac vein to provide systemic venous drainage of the graft, and a duoden-ocystostomy to provide bladder drainage of exocrine secretions[1]. Altho ugh graft survival rates have improved with the use of this technique, potential postoperative problems arise due to the physiologically abnormal exocrine and venous drainage of the pancreas allograft. Bladder drainage of exocrine secretions increased the loss of bicarbonate in the urine, creates electrolyte derangements, and contributes to dehydration leading to a state of metabolic acidosis[2-4]. Pancreatic secretions drained into the bladder also provide a constant source of irritation to the bladder mucosa, accentuating the abnormalities associated with autonomic diabetic dysfunction. This environment subsequently led to recurrent hematuria, infection, and repeated episodes of graft pancreatitis[5-7]. The method of pancreas transplantion with portal venous and enteric drainage can overcome these problems. One of the eariest series of portal pancreatic transplants was reported in 1984[8]. Because of the complex surgical technique, big animal models were used widely in the pancreas transplantation research[9-11], up to now, there has been only portal venous drainage in segmental pancreatic transplantation in rats[12]. In our study, we established an animal model of pancreaticoduodenal transplantation with portal venous drainage through the superior mesenteric vein and enteric drainage in rats in order to achieve a better understanding of the immunology and physiology of this graft.

IMPROVED SOLITARY PANCREAS TRANSPLANT GRAFT SURVIVAL IN THE MODERN IMMUNOSUPPRESSIVE ERA

The results of solitary pancreas (SP) transplantation have traditionally lagged behind those of simultaneous pancreas-kidney (SPK) transplantation. This is one of the chief factors that has limited the wide-scale application of SP transplantation in nonuremic type I diabetic patients. The purpose of this study is to report our present experience with SP transplantation and compare it to a prior experience. Twenty-three SP transplants (14 PAK, 4 PTA, and 5 PASPK) performed since January 1997 were compared to 56 SP transplants (53 PAK, 1 PTA, and 2 PASPK) performed before 1994. Between 1993 and 1997, SP transplants were not performed because of high morbidity in the early experience. Early SP transplants were performed using bladder drainage of exocrine secretions, and enteric drainage without a Roux-en-Y was used in the recent series. In the early era, immunosuppressive therapy included cyclosporine (CsA), azathioprine (AZA), corticosteroids, and in half of the patients, ALG or OKT3. Recent SP transplants received tacrolimus (TAC). mycophenolate mofetil (MMF), corticosteroids, and induction with either anti-thymocyte globulin (n = 9), OKT3 (n = 1), daclizumab (n = 5), or basiliximab (n = 8). The 1-year Kaplan-Meier patient survival was 85% in the early era and 100% in the recent group of patients (p = 0.08). In the previous era, four patients suffered significant decrement in renal function, necessitating dialysis or kidney transplantation following pancreas transplantation. All patients transplanted since 1997 maintain near prepancreas transplant levels of renal function (mean pretransplant serum creatinine (Cr) 1.3 +/- 0.3 mg/dl vs, mean current Cr 1.4 +/- 0.4 mg/dl, p = NS]. The 1-year Kaplan-Meier graft survival (insulin independence) of recent SP transplants was 87%, whereas for prior SP transplants it was 19% (p = 0.0001). The rate of acute pancreas rejection was significantly different between the two groups. Of early SP transplants, 76% experienced at least one rejection episode within the first year. In contrast, 35% of recent SP transplants suffered acute rejection during the same time period (p = 0.04). Current experience with SP transplantation demonstrates improved graft survival and reduced rejection rates with the use of newer immunosuppressive agents.

Early operative intervention for urologic complications of kidney-pancreas transplantation.

Bladder drainage of exocrine secretions during pancreas transplantation can be associated with significant complications. We present a proactive approach to these complications consisting of early cystoenteric conversion (CEC). Although 81 patients underwent pancreas transplant between March 1985 and May 1995; 26 (32%) required CEC. Complications presented as urine leaks, other complications, and refractory metabolic acidosis. There were 13 patients who presented with a urine leak: 12 with acute abdominal pain, and 1 asymptomatic. Serum amylase and creatinine rose a mean of 823 IU and 0.61 mg/dl, respectively. The interval to CEC ranged from 2 to 45 months. One patient died of fungal sepsis. Postoperative complications included duodenojejunal anastomotic bleed (n = 1), negative relaparotomy (n = 1), myocardial infarction (n = 1), graft pancreatitis (n = 1), and wound infection (n = 1). Twelve patients presented with other complications: three women with cystitis (n = 2) or hematuria (n = 1), and nine men with urethritis (n = 6), scrotal edema (n = 2), or dysuria (n = 1), The interval to conversion ranged from 1 to 108 months. There were no deaths. One patient required relaparotomy for anastomotic bleed. One patient was converted because of refractory metabolic acidosis. Admissions and inpatient days were significantly reduced. Overall mortality was 3.8%, morbidity 23.1%, and graft salvage rate 96.1%. Leak-associated mortality was 7.7%, morbidity 38.5%, and graft salvage rate 92.3%. For other complications the mortality was 0, morbidity 7.7%, and graft salvage rate 100%. CEC is a safe, effective treatment for urologic complications of pancreas transplantation. Morbidity and mortality were acceptable; admissions and hospital days were decreased. Early CEC results in superior outcomes and improved quality of life. It is preferable to nondefinitive measures for management of urologic complications of pancreatic transplantation.

The role of whole organ pancreas transplantation in the treatment of type I diabetes

BACKGROUND AND DEMOGRAPHICS: Clinical course was reviewed for 19 whole organ pancreas transplant recipients at UCLA between 11/14/93 and 5/31/95, 18 of which were simultaneous pancreas kidney transplants and 1 of which was an isolated pancreas after kidney transplant. The initial 4 pancreatic grafts were procured by classical warm dissection techniques while the remaining 15 were procured by rapid en bloc technique. Mean recipient age, duration of diabetes, and daily insulin requirements were 38 years, 25 years, and 45 units, respectively. Bladder drainage of exocrine secretions was used primarily in 18 cases and primary enteric drainage in one. All recipients manifested immediate dialysis and insulin independence. Actuarial patient and graft survival were 100% and 89%, respectively, at a mean follow-up of 396 days (range, 150-660 days). Mean maximal serum amylase on the first postoperative day was 366 U/dL. There were no instances of pancreatic graft vascular thrombosis. Three patients experienced pancreatic leaks (16%), 1 of which resulted in graft loss. Six month posttransplant Hgb A1c was within normal range and significantly lower than pretransplantation values (5.1 vs 10.7, P = 0.002). Mean length of initial hospitalization was 15 days, with 100% of patients requiring at least one read mission. Fifty-eight percent of patients experienced rejection episodes. Ninety-one percent of patients responding to a quality of life survey reported improvement in general sense of well-being after transplantation. It is concluded that high rates of success may be possible with whole organ pancreas transplantation, even in new programs. Rapid en bloc dissection is a safe, expeditious method of pancreas procurement. Successful pancreatic transplantation is associated with freedom from exogenous insulin administration, normalization of glycated hemoglobin, and subjective improvement in quality of life. However, this modality is associated with higher rates of rejection and readmission, and longer duration of hospitalization when compared with isolated kidney transplantation.

Conversion of Exocrine Secretions From Bladder to Enteric Drainage in Recipients of Whole Pancreaticoduodenal Transplants

Between September 1984 and August 1991, 265 whole pancreaticoduodenal transplants were done at our institution, with bladder drainage of exocrine secretions through a duodenocystostomy. Seventeen patients subsequently underwent conversion from bladder to enteric drainage at 2 to 64 months after transplant. Eight conversion procedures were done to correct chronic intractable metabolic acidosis due to bicarbonate loss from the allograft: seven to alleviate severe dysuria, presumed secondary to the action of graft enzymes on uroepithelium; one to prevent recurrent allograft pancreatitis, presumed secondary to back pressure from the bladder; and one because of graft duodenectomy for severe cytomegalovirus duodenitis with perforation. None were done to correct technical complications from the initial transplant operation. The conversions were done by dividing the graft duodenocystostomy, then re-establishing drainage through a graft duodenal-recipient jejunal anastomosis. A simple loop of recipient jejunum was used for the duodenojejunostomy in 15 cases, and a Roux limb in two. One of those two cases had a previously created Roux limb that was available for use. The other was in the patient who underwent graft duodenectomy and subsequent mucosa-to-mucosa anastomosis of the pancreatic duct to a newly created Roux limb of jejunum. All patients experienced relief of their symptoms after operation. Two patients had surgical complications (12%), an enterotomy in one case, which was closed operatively, and an enterocutaneous fistula in the other case, which healed spontaneously with bowel rest and parenteral nutrition. The drawback to conversion is loss of urine amylase as a marker for rejection, particularly in recipients of solitary pancreas grafts (n = 5). In recipients of simultaneous pancreas-kidney (SPK) allografts (n = 12), the kidney can still be used to monitor for rejection (two with follow-up < 1 year, 10 with follow-up > 1 year). None of our solitary pancreas recipients, however, have lost graft function (follow-up, 10 to 36 months). The only pancreas allograft loss was in an SPK recipient who also rejected the kidney 6 months after conversion. She received a second SPK transplant with enteric drainage, and is insulin independent and normoglycemic 10 months after retransplantation. Patients converted for metabolic acidosis tended to have impaired renal function (mean creatinine, 2.14 +/- 0.98 mg/dL at time of conversion) due to chronic rejection, progression of native kidney diabetic nephropathy, or cyclosporine toxicity, and possibly could not compensate for bicarbonate loss from the pancreas allograft.(ABSTRACT TRUNCATED AT 400 WORDS)

MONITORING URINARY AMYLASE AND pH IN PANCREAS TRANSPLANTATION WITH URINARY DRAINAGE IN RATS1

Whole pancreas isografts or allografts (ACI donors, RT1a) with bladder drainage of exocrine secretions were performed in Lewis rats (RR1(1] with streptozotocin-induced diabetes. Urinary amylase, pH, and volume and serum glucose were measured daily. They were analyzed alone, or in combination, to determine patterns in deviations from normal values, from isograft control values, or from a posttransplant baseline in relation to rejection (defined as reversion of plasma glucose of greater than 200 mg/dl) in nonimmunosuppressed recipients. Also studied were the sensitivity and specificity by which such deviations predicted rejection. Functioning grafts were associated with increased urinary amylase and pH compared with normal or diabetic controls; urinary volume was less than that of diabetic rats, but greater than that of normal rats. In nonimmunosuppressed allograft recipients (n = 9), rejection occurred at a mean (+/- SD) of 7.78 +/- 0.44 days. Serum glucose rose to above normal (greater than 134 mg/dl) 1 day before rejection in 3 animals (sensitivity 33%, false negative rate 66%; false positive rate in 9 isograft recipients, 44%). Urinary volume dropped below 3 ml at a mean of 3.17 +/- 0.98 days (range 2-5 days) before rejection in 6 animals (sensitivity 66%, false negative rate 33%; false positive rate 0%). Urinary pH fell below 7.25 at a mean of 3.13 +/- 1.81 days (range 1-5 days) before rejection in 8 rats (sensitivity of 89%, false negative rate 11%; false positive rate 29%). Urinary amylase dropped from a posttransplant peak at a mean of 3.56 +/- 1.42 days (range 1-6 days) before rejection in 9 animals (sensitivity 100%, false negative rate 0%; false positive rate 43%), and dropped below 1500 units per 24 hr at a mean of 2.00 +/- 1.32 days (range 1-5 days) before rejection in 8 animals (sensitivity 89%, false negative rate 11%; false positive rate 0%). A drop in urinary amylase combined with a drop in urinary volume or pH occurred at a mean of 3.22 +/- 1.48 days (range 1-5 days) before rejection in 9 rats (sensitivity 100%, false negative rate 0%; false positive rate 0%). In a separate group of 10 allograft recipients, immunosuppression with prednisone and cyclosporine was begun concomitant with, or within 2 days of, the drop in urinary amylase from the peak value; rejection did not occur in 3 animals and was delayed to a mean of 12.0 +/- 5.0 days posttransplant in 7 animals (P less than .05 compared with the nonimmunosuppressed group).(ABSTRACT TRUNCATED AT 400 WORDS)