Pancreas Transplantation Treatment & Management

Updated: Dec 06, 2018
  • Author: Dixon B Kaufman, MD, PhD; Chief Editor: Ron Shapiro, MD  more...
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Treatment

Surgical Care

The surgical techniques for pancreas transplantation are diverse, and no standard methodology is used by all programs. The principles are consistent, however, and include providing adequate arterial blood flow to the pancreas and duodenal segment, adequate venous outflow of the pancreas via the portal vein, and management of the pancreatic exocrine secretions. The native pancreas is not removed. Pancreas graft arterial revascularization typically is accomplished using the recipient right common or external iliac artery. The Y-graft of the pancreas is anastomosed end-to-side. Positioning of the head of the pancreas graft cephalad or caudad is not relevant with respect to successful arterial revascularization.

When the pancreas transplantation is performed simultaneously with kidney transplantation, it is not uncommon for the kidney transplantation to be performed first. The kidney is based on the recipient left iliac vessels. Both organs may be transplanted through a midline incision and placed intraperitoneal.

Occasionally, considering placement of pancreas transplantation based on the left iliac vessels is necessary because of previously placed kidney transplantation on the right side. In this sequential pancreas-after-kidney transplantation procedure, the intra-abdominal approach is used. Mobilization of the left iliac vessels medial to the sigmoid colon is somewhat more challenging.

Most programs have had good experience with enteric drainage of the pancreas transplantation alone. Markers for rejection include clinical signs and symptoms of pancreas graft pancreatitis and measurement of serum amylase or lipase levels coupled with biopsy. The pancreas is sometimes drained into the bladder if a pancreas transplantation alone or pancreas-after-kidney transplantation is performed in order to measure urinary amylase levels as a method of detecting rejection.

Two choices are available for venous revascularization—systemic and portal. No clinically relevant difference in glycemic control has been documented. Currently, approximately 15% of pancreas transplantations are performed with portal venous drainage and the remainder with systemic venous drainage.

Systemic venous revascularization commonly involves the right common iliac vein or the right external iliac vein following suture-ligation and division of the hypogastric veins.

If portal venous drainage is used, dissecting out the superior mesenteric vein (SMV) at the root of the mesentery is necessary. The pancreas portal vein is anastomosed end-to-side to a branch of the SMV. This may influence the methodology of arterial revascularization using a long Y-graft placed through a window in the mesentery to reach the right common iliac artery. Portal venous drainage of the pancreas is more physiologic with respect to immediate delivery of insulin to the recipient liver. This results in diminished circulating insulin levels relative to that in systemic venous-drained pancreas grafts.

Handling the exocrine drainage of the pancreas is the most challenging aspect of the transplantation procedure. Several methods exist. Very few programs use duct injection. Pancreatic exocrine drainage is handled by means of anastomosis of the duodenal segment to the bladder or anastomosis to the small intestine. Currently, approximately 80% of pancreas transplantations are performed with enteric drainage; the remaining 20% are performed with bladder drainage.

See the images below.

Solitary pancreas transplantation with enteric dra Solitary pancreas transplantation with enteric drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.
Solitary pancreas transplantation with bladder dra Solitary pancreas transplantation with bladder drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.

The bladder-drained pancreas transplantation was a very important modification introduced in about 1985. This technique significantly improved the safety of the procedure by minimizing occurrence of intra-abdominal abscess from leakage of enteric-drained pancreas grafts.

With the successful application of the new immunosuppressant agents and the reduction of the incidences of rejection, enteric drainage of the pancreas transplantations has enjoyed a successful rebirth. Enteric drainage of pancreas grafts is physiologic with respect to the delivery of pancreatic enzymes and bicarbonate into the intestines for reabsorption. Enterically drained pancreases can be constructed with or without a Roux-en-Y. The enteric anastomosis can be made side-to-side or end-to-side with the duodenal segment of the pancreas. The risk of intra-abdominal abscesses is extremely low, and avoidance of the bladder-drained pancreas has significant implications with respect to the potential complications that include the following: bladder infection, cystitis, urethritis, urethral injury, balanitis, hematuria, metabolic acidosis, and the frequent requirement for enteric conversion.

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Medical Care

Immunosuppression must be taken for as long as the patient's transplanted organs are functioning. Immunosuppression cannot be stopped, or rejection of the organs will ensue. 

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Transplantation outpatient follow-up care

During hospitalization, transplant recipients are prepared for discharge with respect to expectations of medical compliance, education about the pharmacology of their new immunosuppression medications, and lifestyle issues. Patients usually are provided a booklet that delves into the above-mentioned topics.

Following successful pancreas transplantation, no dietary restrictions are required. In fact, the diet can be liberalized to include virtually anything because blood sugar control is restored to normal.  Extreme contact sports probably should be avoided to prevent accidental trauma to the newly placed intra-abdominal organs.

Typical visit schedule following discharge from the hospital is as follows:

  • Two or 3 visits in week 1

  • Two visits in week 2

  • One visit in week 3

  • Monthly thereafter, until 6 months posttransplantation

  • Every 3 months through the first year

  • Every 6 months through the second year

  • Annually thereafter

Laboratory follow-up studies occur in the transplantation clinic and at a local laboratory near the patient's home. A typical schedule is as follows:

  • Every Monday, Wednesday, and Friday in month 1

  • Every Monday and Thursday in month 2

  • Every Monday in months 3-6

  • Every other week in months 7-24

  • Every month after 24 months

Typical laboratory evaluation includes complete blood count, electrolytes, BUN, creatine, glucose, serum amylase, and immunosuppression blood levels (if transplantation recipient is receiving cyclosporine, tacrolimus, or sirolimus).

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Complications

Rejection

The first criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established in 2008. At the time, only tentative criteria for the diagnosis of antibody-mediated rejection (ABMR) were characterized. Since then, the criteria have been reviewed and updated approximately every two years to account ongoing advances in the understanding of ABMR. [16]

Surgical and nonimmunological complications of pancreas transplantation

Surgical complications are more common after pancreas transplantation as compared to kidney transplantation. Nonimmunological complications of pancreas transplantation account for graft losses in 5-10% of cases. These occur commonly within 6 months of transplantation and are as important an etiology of pancreas graft loss in SPK transplantation as acute rejection is.

Thrombosis

Vascular thrombosis is a very early complication, typically occurring within 48 hours and usually within 24 hours of the transplantation. [8]  This generally is due to venous thrombosis of the pancreas portal vein. The etiology is not defined entirely but is believed to be associated with reperfusion pancreatitis and the relatively low-flow state of the pancreas graft. Prudent selection of donor pancreas grafts, short cold-ischemia times, and meticulous surgical technique are all necessary to minimize graft thrombosis.

Transplantation pancreatitis

Pancreatitis of the allograft occurs to some degree in all patients postoperatively. Temporary elevation in serum amylase levels for 48-96 hours after transplantation is common. These episodes are transient and mild, without significant clinical consequence. Interestingly, patients undergoing simultaneous kidney-pancreas transplantation commonly have a greater degree of fluid retention for several days after transplantation, as compared to a recipient of a kidney transplant alone. Though not proven, this may be related to the graft pancreatitis that ensues in the perioperative period. The retained fluid is mobilized early postoperatively. It is important to minimize the risk of delayed kidney graft function by shortening cold-ischemia time so that the retained third-spaced fluid may be eliminated rapidly to avoid an episode of heart failure or pulmonary edema.

Complications of bladder-drained pancreas transplantation

Bladder-drained pancreas transplantation is a safer procedure than enteric-drained pancreas transplantation with respect to the possibility of intra-abdominal abscess. However, it is hampered by numerous less morbid complications. The pancreas transplantation eliminates approximately 500 mL of richly bicarbonate fluid with pancreatic enzymes into the bladder each day. Change in pH level of the bladder accounts, in part, for a greater increase in urinary tract infections. In some cases, a foreign body, such as an exposed suture from the duodenocystostomy, acts as a nidus for urinary tract infections or stone formation.

Acute postoperative hematuria of the bladder-drained pancreas usually is due to ischemia/reperfusion injury to the duodenal mucosa or to a bleeding vessel on the suture line that is aggravated by the antiplatelet or anticoagulation protocols to minimize vascular thrombosis. These cases are self-limited but may require change in bladder irrigations and, if severe, cystoscopy to evacuate the clots. Occasionally, performing a formal open cystotomy and suture ligation of the bleeding vessel is necessary intraoperatively. If relatively late chronic hematuria occurs, transcystoscopic or formal operative techniques may be necessary treatments.

Sterile cystitis, urethritis, and balanitis may occur after bladder-drained pancreas transplantation. This is due to the effect of the pancreatic enzymes on the urinary tract mucosa and is experienced more commonly in male recipients. Urethritis can progress to urethral perforation and perineal pain. Conservative treatment with Foley catheterization and operative enteric conversion represent the extremes of the continuum of treatment.

Metabolic acidosis routinely develops as a consequence of bladder excretion of large quantities of alkaline pancreatic secretions. Patients must receive oral bicarbonate supplements to minimize the degree of acidosis. Because of the relatively large volume losses, patients also are at risk of episodes of dehydration exacerbated by significant orthostatic hypotension.

Reflux pancreatitis can result in acute inflammation of the pancreas graft, mimicking acute rejection. It is associated with pain and hyperamylasemia and is believed to be secondary to reflux of urine through the ampulla and into the pancreatic ducts. Often, the urine is found to be infected with bacteria. This frequently occurs in a patient with neurogenic bladder dysfunction. This complication is managed by Foley catheterization. Reflux pancreatitis will resolve quickly. The patient may require a complete workup of the cause of bladder dysfunction, including a pressure-flow study and voiding cystourethrogram. Interestingly, in older male patients, even mild hypertrophy of the prostate has been described as a cause of reflux pancreatitis. If recurrent graft pancreatitis occurs, enteric conversion may be indicated.

Urine leak from breakdown of the duodenal segment can occur and is usually encountered within the first 2-3 months following transplantation but can occur years following transplantation. This is the most serious postoperative complication of the bladder-drained pancreas. The onset of abdominal pain with elevated serum amylase, which can mimic reflux pancreatitis or acute rejection, is a typical presentation. A high index of suspicion for urinary leak is necessary to make the diagnosis accurately and swiftly. Supporting imaging studies using a cystogram or CT scan are necessary to confirm the diagnosis. Operative repair is usually required with exploration. The degree of leakage can be determined best intraoperatively, and proper judgment can be made whether direct repair is possible or more aggressive surgery involving enteric diversion or even graft pancreatectomy is indicated.

Complications of enteric-drained pancreas transplantation

The most serious complication of the enteric-drained pancreas transplantation is leak and intra-abdominal abscess. This serious problem usually occurs 1-6 months after transplantation. Patients present with fever, abdominal discomfort, and leukocytosis. A high index of suspicion is required to make a swift and accurate diagnosis. Imaging studies involving CT scan are very helpful.

Percutaneous access of intra-abdominal fluid collection for Gram stain and culture is essential. The flora typically is mixed with bacteria and often fungus, particularly Candida. Broad-spectrum antibiosis is essential. Surgical exploration and repair of the enteric leak is necessary. A decision must be made on whether the infection can be eradicated without removing the pancreas allograft. Incomplete eradication of the infection will result in progression to sepsis and multiple organ system failure. Peripancreatic infections can result in development of a mycotic aneurysm at the arterial anastomosis that could cause arterial rupture. Transplantation pancreatectomy is indicated if mycotic aneurysm is diagnosed.

Occurrence of intra-abdominal abscess has been reduced greatly with greater recognition of the criteria for suitable cadaveric pancreas grafts for transplantation. Improved perioperative antibiosis, including antifungal agents, has contributed to the decreased incidence of intra-abdominal infection, as well. No convincing evidence exists that a Roux-en-Y intestinal reconstruction decreases its incidence. Perhaps the most significant contribution to reducing the incidence of intra-abdominal abscess is the efficacy of the immunosuppressive agents in reducing the incidence of acute rejection and thereby minimizing the need for intensive antirejection immunotherapy.

GI bleeding occurs in the enteric-drained pancreas from a combination of perioperative anticoagulation and bleeding from the suture line of the duodenoenteric anastomosis. This is self-limited and will manifest as diminished hemoglobin level associated with heme-positive or melanotic stool. Conservative management will suffice; the necessity for reoperative exploration is extremely unusual.

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