Pancreas Transplantation with Portal Venous Outflow
Jeffrey Rogers
Robert J. Stratta
DEFINITION
Vascularized pancreas transplantation was initially developed as a means to reestablish endogenous insulin secretion responsive to normal feedback controls. As of December 2010, more than 35,000 pancreas transplants were reported to the International Pancreas Transplant Registry and nearly 9,000 to the Collaborative Transplant Study databases.1,2 Pancreas transplantation in diabetic patients is divided into three major categories: those performed simultaneously with a kidney (SPK) transplant, usually from a deceased donor; those performed after a successful kidney (PAK) transplant in which the kidney came from either a living or deceased donor; and pancreas transplantation alone (PTA) in the complete absence of a kidney transplant. The latter two (PAK and PTA) categories are usually combined together as solitary pancreas transplants. The total number of pancreas transplants steadily increased until 2004 but has since declined, particularly in the PAK category.1,3 In the last decade, era analyses have demonstrated that deceased donor recovery rates and additions to the waiting list have decreased; discard rates and waiting times have increased; and the proportion of recipients who are older, black, have a higher body mass index (BMI), or are characterized as having type 2 diabetes have all increased.1,3 The majority (75%) of pancreas transplants are performed as SPK transplants, whereas approximately 16% are performed as PAK and 9% as PTA transplants, respectively.1,3
Over 80% of enteric-drained pancreas transplants are performed with systemic (iliac or vena cava) venous delivery of insulin, resulting in peripheral hyperinsulinemia.1 In the nontransplant setting, chronic hyperinsulinemia has been associated with insulin resistance, dyslipidemia, accelerated atherosclerosis, and macroangiopathy. To improve the physiology of pancreas transplantation, a surgical technique of intraperitoneal portal venous drainage using the superior mesenteric vein (SMV) was developed by Gaber et al.4 and subsequently refined to a “retroperitoneal” approach by Boggi et al.5 This approach combines portal venous delivery of insulin with enteric drainage of the exocrine secretions (portal-enteric technique). However, the potential of portal-enteric drainage has never been fully realized as it currently accounts for only 18% of SPK and PAK and 10% of PTA transplants.1 A number of studies have demonstrated no major or consistent differences in outcomes for bladder-drained or enteric-drained pancreas transplants with either portal or systemic venous drainage.6,7,8,9,10,11 Although nearly all pancreas transplants are currently performed with one of the three previously-mentioned techniques, current philosophy dictates that the most appropriate technique to be performed is the one with which the individual surgeon feels most comfortable. The remaining focus of this chapter will be on the technical aspects of whole organ pancreaticoduodenal transplantation with portal venous and enteric exocrine drainage.
DONOR SELECTION AND MANAGEMENT
Donor selection and management are of paramount importance for minimizing technical failure and optimizing long-term outcomes in pancreas transplantation. All of the following principles apply regardless of the intended technique or type of pancreas transplant that is planned. Indications, contraindications, and risk factors for successful pancreas donation are listed in Table 1.12
Most organ donors who are appropriate for kidney, liver, heart, and lung donation are also suitable for pancreas donation.
The ideal pancreas donor is brain dead as a result of trauma rather than cerebrovascular disease, ranges in age from 10 to 40 years, and ranges in weight from 30 to 80 kg (BMI <27.5 kg/m2).
Terminal hyperglycemia is not an exclusion criterion for pancreas procurement and transplantation. However, tight glucose control with insulin is advisable to minimize the potential for hyperglycemia-related toxicity to pancreatic beta cells, which may be associated with posttransplant graft dysfunction.
Hemoglobin A1c or serum C-peptide levels may be helpful in assessing donors with severe or protracted hyperglycemia, a prior history of hyperglycemia (e.g., gestational diabetes), or a strong family history of diabetes. These studies are not always readily available and may be misleading in the setting of massive transfusions or resuscitation.
When hemodynamic instability persists despite adequate volume and hormonal resuscitation, then vasoactive drug administration is necessary. Use of vasopressors is considered a risk factor for graft dysfunction by influencing the pancreatic microcirculation. However, a number of studies have shown that high-dose vasopressor administration in donors does not directly affect pancreas graft function.
Terminal administration of vasodilatory agents (such as papaverine or phentolamine) just prior to cross-clamping for organ recovery may counteract some of the vasospastic effects of hypotension, hypothermia, acidosis, warm ischemia, and high-dose vasopressor support.
Although serum glucose, amylase, and lipase levels may be helpful in determining the quality of a pancreas allograft, there are many variables in the organ donor that render these tests less helpful.
Serum glucose levels frequently are elevated in organ donors due to relative insulin resistance associated with strokes or brain injuries, intravenous fluids with high dextrose content that are frequently used to correct hypernatremia, and hyperglycemia resulting from
steroids administered as part of a brain edema protocol. Hyperamylasemia can result from intestinal injury or injury to the salivary glands in cases of head trauma. Hyperlipasemia is more specific to the pancreas and should raise concern for pancreatic injury, inflammation, or edema. Another indication that the pancreas may be compromised includes deterioration in the function of other organs such as progressive renal failure or elevation of liver enzymes. The primary data required to decide if a particular organ donor is suitable for an intended recipient are routinely provided by the host organ procurement organization.
Table 1: Deceased Donors for Pancreas Organ Donation
Indications
Declaration of brain death with informed consent
Age 6-60 y (ideal 10-40 y)
Weight 25-120 kg (ideal 30-80 kg), body mass index (BMI) <32 kg/m2 (ideal <27.5 kg/m2)
Hemodynamic stability with adequate perfusion and oxygenation
Absence of malignancy (unless skin or low-grade brain cancer)
Absence of infectious or transmissible diseases (i.e., tuberculosis, syphilis, hepatitis, AIDS)
Negative HIV, hepatitis B and C serology (provided that intended recipient has negative serology)
Normal glycosylated hemoglobin level (only needed in cases of severe hyperglycemia, extreme obesity, or positive family history of diabetes)
Absence of known parenchymal/intrinsic pancreatic disease
Contraindications
History of diabetes mellitus (type 1 or 2, or gestational)
Unexplained meningitis or cause/mechanism of death
Disseminated intravascular coagulation
BMI >35 kg/m2 (unless donor is young and otherwise “ideal”)
Previous pancreatic surgery, moderate to severe pancreatic trauma
Pancreatitis (active acute or chronic)
Severe intraabdominal sepsis, untreated major (active) infection
Chronic (>5 y) alcohol abuse
Active or current intravenous drug abuse, homosexuality, incarceration, or high-risk sexual behavior
Prolonged hypotension or hypoxemia with evidence for significant end-organ (kidney, liver) damage
Prolonged warm ischemia (>30 min)
Severe atherosclerosis
Inexperienced retrieval team
Severe fatty infiltration of pancreatic parenchyma, severe uncorrectable pancreatic edema
Risk factors
Donation after cardiac death
Massive transfusions or fluid resuscitation
Prior splenectomy
Mild to moderate obesity (BMI >30 kg/m2)
Acute alcohol abuse
Recent history of intravenous drug abuse, homosexuality, incarceration, or high-risk sexual behavior
Aberrant hepatic/splenic/superior mesenteric/pancreatic artery anatomy
Positive VDRL/RPR serology
Positive hepatitis C serology (only for hepatitis C-positive recipients)
Positive hepatitis B core antibody serology (only for hepatitis B surface antibody-positive recipients)
Mild intraabdominal sepsis (not extending into retroperitoneum)
Treated major (active) infection (including bacteremia)
Prolonged length of hospital stay (>7 d); prolonged intensive care unit stay (>3-5 d)
Donor age older than 45 y
Cardiovascular or cerebrovascular cause of brain death
Mild to moderate fatty infiltration or pancreatic edema
Mild to moderate donor instability with vasopressor requirements
Mild pancreatic trauma, duodenal/pancreatic or retroperitoneal hematoma
Mild to moderate atherosclerosis
Long-standing/poorly controlled hypertension
Elevated pancreatic enzymes
Excessive (>4-5 L) in situ aortic or back-table flush
Prolonged extraction time (>1 h from time of cross-clamping)
RPR, rapid plasma reagin; VDRL, venereal disease research laboratory.
Methods of systematic, quantitative assessment of pancreas donor quality have been developed that are predictive of either pancreas donor use or graft failure. The best indication of suitability of a pancreas allograft for transplantation is the appearance of the organ at the time of procurement.
It is extremely important that the recovery surgeon be experienced in the proper procurement techniques in order to minimize handling of the pancreas and provide the recipient surgeon with an appropriate description of fat content, severity of graft edema, and quality of the vasculature.
One of the most important determinants of pancreas suitability is inspection of the organ by an experienced pancreas transplant surgeon, which is best achieved by complete mobilization of the tail and body of the pancreas up into the operative field using the spleen as a handle.
The portal vein is transected halfway between the superior border of the pancreas and the inferior border of the liver. As long as the venous confluence is intact, however, the pancreas can be transplanted with portal venous drainage. If necessary, donor iliac vein may be required for venous reconstruction if the portal vein stump is less than 1 cm in length, depending on the venous anatomy in the recipient.
In addition to the procurement of the pancreas itself, the success of the transplant procedure relies on proper back-table reconstruction of the arterial vasculature, usually with a donor iliac or carotid artery “Y” bifurcation graft.
From the perspective of portal-enteric pancreas transplantation, the portal vein length is as described previously.
Because a long arterial Y-graft is usually required to pass through the distal bowel mesentery to reach the common or external iliac artery in the recipient, recovery of a long common iliac artery bifurcation graft (with long external and internal iliac limbs) in the donor is necessary.
The duodenum is often flushed prior to cross-clamping through a nasogastric tube positioned well beyond the pylorus with amphotericin B solution (50 mg/250 mL D5W) or Betadine® solution or both, although this is not absolutely required for enteric-drained allografts.
TECHNIQUES
BACKBENCH PREPARATION OF THE PANCREAS
The back-table preparation of the pancreas allograft is one of the most crucial steps in achieving technically successful portal-drained pancreas transplantation.13 The back-table preparation is the best and final opportunity to scrutinize the graft for quality in terms of fat content or fibrosis; assess texture; and to establish that there are no anatomic abnormalities, undetected trauma, or surgical damage. The details of back-table preparation are noted in Chapter 38 of this volume. Details specific to portal venous drainage are noted in the following text.
Examination of the graft: The container or bag containing the pancreas allograft and preservation solution is opened, allowing for initial examination of the pancreas allograft. The volume and composition of the preservation solution should be noted, and either additional cold sterile preservation solution can be added or the pancreas can be immersed in fresh solution if the existing solution is bloody, turbid, or discolored. It is important to note that iced slush should never come in direct contact with the pancreas and that the pancreas should not be placed in the slush machine during or after preparation because of concerns about freezing. In addition, because the backbench preparation may take 2 to 3 hours, it is important to keep the pancreas from rewarming by maintaining adequate amounts of iced slush in the basin containing the organ. This is the best opportunity to scrutinize the pancreas for quality in terms of fat content or fibrosis and to assess the texture of the pancreatic parenchyma. All aspects of the pancreas should be inspected for injury to the pancreatic parenchyma and for the presence of hematomas. This is also the time that the size and quality of the vasculature should be assessed in order to determine if the pancreas is transplantable. If significant atherosclerosis is present in the superior mesenteric artery (SMA) or splenic artery or both, consideration may be given to aborting the procedure because of the risk of thrombosis. Additionally, the back table may be the only time that abnormalities such as mass lesions, splenic artery aneurysms, accessory spleens, or duodenal diverticula may be identified. Although these findings are not necessarily contraindications to transplantation, they should be addressed and documented prior to implantation.
Any donor vessels retrieved for arterial reconstruction need to be carefully inspected at this point because failure to identify atherosclerotic vascular disease or surgical damage to these vessels from improper technique or traction injuries may significantly jeopardize the outcome of the subsequent transplant procedure.
Preparation of the duodenum: On the backbench, the proximal staple line may be inverted with either running 3-0 polydioxanone (PDS) or interrupted seromuscular Lembert 3-0 or 4-0 silk sutures. With respect to the distal staple line, if the pancreas is to be transplanted with enteric exocrine drainage, it is not necessary to trim the distal second and third portions of the duodenum away from the pancreas. The distal staple line can be inverted as previously mentioned at the junction of the third and fourth portions of the duodenum proximal to the ligament of Treitz and the transplant can be performed as a complete pancreaticoduodenal graft. Leaving most of the duodenum attached to the pancreas significantly shortens the “bench” time and may preserve blood supply and collateral flow to the head of the pancreas while minimizing pancreatic leak that could develop from dissecting the duodenum off the pancreas. It also preserves a number of options for performing the enteric anastomosis in the recipient either to the donor’s proximal, mid-, or distal duodenum.
Vascular preparation and reconstruction: Currently, the most common technique for arterial reconstruction of the dual artery blood supply of the pancreas is to retrieve a naturally occurring bifurcating artery from the donor to be used as an interposition arterial Y-graft. The most commonly used bifurcation is that of the common iliac artery into the external and internal iliac arteries, which are anastomosed to the SMA and splenic arteries, respectively (FIG 1). In cases of systemic venous drainage or retroperitoneal portal venous drainage, the arterial interposition Y-graft does not have to be particularly long, and the best size match is to anastomose the external iliac artery to the SMA and the internal iliac artery to the splenic artery. However, with nonretroperitoneal portal venous drainage, a long Y-graft is required and the best way to maximize length is to perform anastomoses between the longer limb of the external iliac artery to the shorter splenic artery and the shorter limb of the internal iliac artery to the longer SMA. On occasion, an extension graft (of distal external iliac artery or other donor arterial graft) may need to be anastomosed
end-to-end to the common iliac conduit in order to further lengthen the arterial reconstruction (FIG 1).
FIG 1 • Reconstruction of the dual artery blood supply of the pancreas with an interposition donor arterial Y-graft. The most commonly used bifurcation is that of the common iliac artery into the external and internal iliac arteries, which are anastomosed to the SMA and splenic arteries, respectively. An extension graft of distal external iliac artery can be anastomosed end-to-end to the common iliac conduit in order to further lengthen the arterial reconstruction.
Most recovery surgeons transect the portal vein in situ at the level of the coronary or left gastric vein, which may or may not leave an adequate length of portal vein with the pancreas allograft. As long as the venous confluence is intact, however, the pancreas can usually be transplanted. Rarely, donor iliac vein may be required for venous reconstruction if the portal vein stump is less than 1 cm in length, depending on the venous anatomy in the recipient. On the backbench, the portal vein is placed on gentle traction with fine sutures and dissected back toward the confluence of the SMV and splenic vein, ligating and dividing the superior pancreaticoduodenal and coronary veins if present. If the portal vein is greater than 3 cm in length, it may need to be shortened. Some centers prefer to shorten the portal vein as much as possible by dividing it just distal to the confluence of the SMV and splenic and vein. Although it becomes technically more difficult to perform the venous anastomosis in the recipient, shortening the portal vein has the advantage that the vein may be too short to kink and this also protects from compression by the surrounding tissues.
SURGICAL IMPLANTATION WITH PORTAL VENOUS OUTFLOW
Although bladder, renal pelvic, and ureteral drainage of the exocrine secretions of the pancreas is technically feasible concomitant with portal venous drainage,14,15 nearly all pancreas transplants with portal venous outflow are performed in conjunction with enteric drainage of the exocrine secretions (portal-enteric technique). In addition, although techniques of portal venous outflow have been described using either the recipient splenic vein,15,16,17 inferior mesenteric vein,18 or portal vein directly,14 “portal venous” outflow almost always implies use of the recipient’s SMV for venous drainage of the pancreas allograft with the head of the pancreas directed cephalad and the body and tail directed caudally in the recipient.
Incision and graft placement: Most pancreas transplants are performed through a vertical midline abdominal incision, which preserves all possible options for transplantation of the pancreas as well as simultaneous placement of a kidney through the same incision when applicable. In general, midline incisions are associated with fewer wound infections, although the key concepts are taking advantage of the intraperitoneal lymphatic circulation and permeability for internal absorption of peripancreatic secretions in conjunction with preventing proximity between the healing wound and the reperfused pancreas.19 In the absence of a kidney transplant, the incision may extend from the midepigastrium to 2 to 3 cm above the symphysis pubis; with a simultaneous kidney transplant, the incision should extend to the symphysis pubis for better pelvic exposure.
Unlike other methods of pancreas transplantation, the portal-enteric technique is a midabdominal rather than a pelvic procedure. For this reason, it tends to make the venous and enteric anastomoses “easier” because the pancreas is positioned more cephalad and anterior in the abdominal midline. However, the arterial anastomosis and exposure may be more challenging because of the need for a long Y-graft that traverses through the distal ileal mesentery.
The procedure can also be performed through a transverse abdominal19,20 or J-shaped iliac incision; with the latter, it is recommended that if an extraperitoneal approach is taken, then a peritoneal window be created after the vascular anastomoses for performance of the bowel anastomosis and to facilitate absorption of potential leaks and perigraft fluid collections.Related posts:
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