- Email: [email protected]
Pancreas retransplantation
C H A P T E R
27 Pancreas retransplantation Ty B. Dunn*, Karthik V. Ramanathan† *University of Pennsylvania, Philadephia, PA, USA †Department of Surgery, University of Minnesota, Minneapolis, MN, United States O U T L I N E Introduction
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Timing
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Historical perspective
339
Surgical approaches
344
Indications and considerations
340
Postoperative care
345
Retransplant type and outcomes
341
Summary
345
Recipient evaluation
342
References
345
Donor selection
344
Introduction
Historical perspective
Successful pancreas transplantation continues to be the only treatment for insulin-dependent diabetes that durably restores euglycemia and metabolic control. The return of euglycemia and freedom from constant monitoring and multiple daily insulin injections or wearing a pump/monitor can significantly improve quality of life, stop the progression of diabetic complications, and in some cases is a life-saving procedure. Failure of a pancreas transplant reexposes the patient to their chronic disease state and its associated problems of dysglycemia, which can be physically and emotionally devastating. Since pancreas retransplantation is infrequently performed, few transplant centers or surgeons have substantive experience with the procedure which is currently now offered at a decreasing number of centers. This chapter outlines the history and outcomes of pancreas retransplant, key concerns in the evaluation of the retransplant candidate, surgical considerations, and an overview of the nuances of the different types and risks of pancreas retransplantion.
It was not until 12 years after the world’s first pancreas transplant was performed in 1966 that the first pancreas retransplant was accomplished.1,2 In the United States (US), the number of pancreas retransplant operations increased in parallel with that of primary pancreas transplantation and peaked in 2004 at 130 (8.8% of all pancreas transplants that year) and has since decreased to 44 (4.3% of all pancreas transplants) in 2016 [based on Organ Procurement and Transplantation Network (OPTN) data as of April 20, 2018] (Fig. 1). In contrast, about 11% of the pancreas transplant waitlist is comprised of candidates awaiting retransplantation.3 The overall number of retransplant cases performed outside the United States is comparatively lower and in decreased proportion to primary pancreas transplants, but incomplete reporting limits a more granular review of retransplant activity outside the United States [A. Gruessner ([email protected]), e-mail July 30, 2018]. According to OPTN data collected since 1988, a total of 184 transplant centers in the United States at some time or
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Pancreas transplantation in the United States 1800 1600 1400 1200 1000 800 600 400 200 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
0
Primary transplant
Retransplant
FIG. 1 Primary and repeat pancreas transplant activity in the United States.
another have performed a pancreas transplant. Of these centers, 74% have reported doing some type of pancreas retransplant (solitary pancreas or in combination with kidney). Of these, only 24 centers (13%) have performed 20 or more retransplants of any type. Contemporary activity (the 10 years spanning 2007–2016) reveals just 14 centers (located in 7 of the 11 UNOS regions) performed 10 or more retransplants during those 10 years. Of the 120 pancreas transplant centers that were active in the year 2016, 24 centers performed a retransplant, and only half4 of these 24 centers (10% of active centers) did more than one retransplant, highlighting the relative infrequency of the procedure. The increased complexity of pancreas retransplantation, in tandem with its low frequency, makes it difficult for a center (as well as an individual surgeon) to maintain currency and provide trainees adequate exposure to this relatively rare operation. In the 20 years after the first pancreas retransplant was performed, small series of pancreas retransplants were published from the most active centers. Collectively, these reports demonstrated the feasibility of pancreas retransplantation and showed that clinical outcomes were not far below those of contemporaneous primary pancreas transplants.5–10 During this same period, pancreas transplantation as a whole was remarkable for very high surgical complication rates and 1-year graft survival below those of other solid organ transplants. However, improvements in donor selection and organ procurement, technical aspects of pancreas transplantation, and medical management of the recipient all have contributed to the significantly enhanced outcomes we expect today. With the field further maturing over the subsequent 20 years [with the routine use of induction immunosuppression, calcineurin inhibitors (CNI), valganciclovir, and modern histocompatibility techniques], improvements in outcomes of pancreatic
retransplantation have continued to be congruent with those seen in contemporaneous primary transplantation. Compared to primary transplants, outcomes of pancreas retransplantation in the modern era are notable for a similar risk of technical failure, and only slightly decreased 1-year graft survival rates. Longer term graft survival is significantly decreased for cases of pancreas retransplant compared to primary transplant, which is consistent with all other deceased donor solid organ transplant types.4,11,12 Patient survival after pancreas retransplantation in the modern era is excellent and not significantly different from that seen after primary transplantation.4,11 Results of the largest series of pancreas retransplants are summarized in Table 1.4,6,8,9,11,13–16 Because the overall outcomes of primary pancreas transplantation have improved over time, the age of the typical pancreas transplant candidate has increased, and medical management of diabetes has improved, it is not surprising that pancreas retransplants are becoming less common. In tandem, patient survival for all types of primary pancreas transplant continues to increase.3 It is important to recognize that a significant number of patients with a failed pancreas transplant may benefit from retransplantation. One-year patient and graft survival rates for repeat pancreas transplants are near those of primary transplant. Some patients will be best served by an opportunity for retransplantation, especially when they require kidney retransplantation or remain on immunosuppression with a well-functioning kidney transplant.
Indications and considerations Diabetics who suffer from severe hypoglycemic episodes or progression of microvascular complications
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Retransplant type and outcomes
TABLE 1 Summary of studies reporting 20 or more pancreas retransplants Author Year
Center
Years
N
Type
TF
1 Yr AR
1 Yr GS
1 Yr PS
FU
Buron 2013
Lyon Geneva 1976–2008
37
70% PAK 27% SPK 3% PTA
16 (43%)
NR
64%
100%
7.8 yr
Morel 1991
U Minn
1978–1989
68
35% PAK 18% SPK 47% PTA
16 (24%)
57%
43%
89%
NR
Humar 2000 U Minn
1994–1997
26
46% PAK 35% SPK 19% PTA
7 (27%)
55%
69%
96%
NR
Sutherland 2001#
U Minn
1978–2000
191
49% PAK 19% SPK 32% PTA
NR
NR
51% 64% 45%
88% 83% 90%
NR
Rudolph 2015#
U Minn
1978–2012
415 (included 3rd and 4th Tx)
48% PAK 21% SPK 30% PTA
66 (16%)
28%
76%
88%
NR
Genzini 2006 Sao Paulo
1996–2005
20
NR
2 (10%)
NR
85%
95%
2 yr
Rudolph 2015*
U Minn
2003–2012
155 (including 3rd and 4th Tx)
57% PAK 14% SPK 29% PTA
17 (11%)
34%
81%
90%
4.7 yr PAK 4.6 yr SPK 4.3 yr PTA
Rudolph 2015*
U Minn
2003–2012
125 (restricted to 2nd Tx)
56% PAK 14% SPK 30% PTA
14 (11%)
35%
73%
96%
4 yr PAK 4.8 yr SPK 3.5 yr PTA
Fridell 2015
U Indiana
2003–2013
20
65% PAK 25% SPK 10% PTA
0 (0%)
5%
90%
95%
4.6
TF, technical failure; AR, acute rejection; GS, graft survival; PS, patient survival; FU, mean follow-up; NR, not reported. The symbol # indicates that the publication includes previously published cases, and * denotes a subanalysis of a modern retransplant cohort.
typically have a significant chronic disease burden and come to transplant evaluation after other less invasive therapies fail. The indications for pancreas retransplantation are the same as for primary transplants, with special consideration of a few characteristics that are of particular importance to retransplantation—that of a vetted ability to adhere to the requisite posttransplant medication and follow-up protocols, sufficient cardiopulmonary reserve to withstand a major operation, and the availability of surgical targets suitable for anastomosis. It is important to avoid increased immunologic risk grafts (positive crossmatch or with donors to whom the candidate has a significant amount of donor-specific anti HLA antibody). Of course, these characteristics are also important for primary transplants but carry special weight when considering a retransplant opportunity. For the individual candidate, factors that contributed to the technical failure of a primary allograft must be sought and corrected (or mitigated) during the pre-, peri-, and postoperative phases of the retransplant. In the case of early graft failure due to thrombosis, a comprehensive thrombophilia evaluation should be done and a plan for
anticoagulation at retransplant established. Graft failures due to pancreatitis require a more conservative approach to donor selection and the predicted cold ischemic time. Candidates who experience late graft failures or allograft pancreatectomy may become sensitized to HLA, which may decrease the likelihood of finding a match for retransplantation.17 For these candidates, being open to importing the graft from regional or national donor service areas, in combination with using a virtual crossmatch approach or shipping blood for crossmatching prior to final organ allocation may be highly productive.18 Even with a negative crossmatch, retransplantation has been associated with a significantly increased risk of early and mid-term immunologic graft loss.4
Retransplant type and outcomes Currently, the most common type of pancreas retransplant is PAK, which represents over 50% of all pancreas retransplants.3, 19 While about 2% of SPKs have been consistently classified as pancreas retransplants, over the
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FIG. 2 Pancreas retransplant frequency (Panel A) and proportion of overall transplants of that type (Panel B) by year in the United States, as reported by the International Pancreas Transplant Registry (IPTR). PAK, pancreas after kidney; PTA, pancreas transplant alone; and SPK, simultaneous pancreas kidney.
past several years PAK retransplants have increased and now comprise over 30% of all PAK cases (Fig. 2A and B). Importantly, there has not been an increase in SPK retransplants since the new allocation system went into effect.20 The PAK retransplant cases are most commonly performed after a primary SPK or PAK transplant type, and repeat SPKs are typically performed after a primary SPK (Fig. 3). Pancreas transplant alone (PTA) recipients have the highest risk of rejection but may benefit from retransplantation, in particular, if the first graft was lost to technical failure. Recipients of PTA are disproportionately more female and younger than other types of pancreas recipients and do not have ESRD, all of which are key factors that
likely contribute to the highest observed rates of posttransplant patient survival. Technical failure of the pancreas allograft (within the first 90 days posttransplant), while slightly decreased over time, continue to affect about 10% of solitary pancreas transplants (PTA and PAK), in contrast to about 5% of SPKs; avoidance of multiple risk factors is key to minimizing this devastating outcome.20,21 Surgical and immunologic risks are increased for the pancreas retransplant candidate. An SPK retransplant is more technically challenging since about 75% of recipients undergo removal of the failed primary allograft either before or during the retransplant operation.22 Incidental procedures such as appendectomy, lysis of adhesions, and herniorrhaphy are also not infrequently performed during retransplantation. The anatomy after pancreatectomy often dictates alternate surgical techniques such as creation of a Rouxen-Y bowel anastomosis or placement of the graft higher (on the inferior vena cava) or lower (external iliac artery) or on the left iliac system for systemically drained grafts, although portal venous drainage technique is an option for dealing with hostile iliac veins and has even been successfully reused.23 Candidates for retransplantation are more likely to be highly sensitized, which, together with the lower frequency of deceased donors suitable for pancreas donation compared to kidney donation, can make wait times longer for a retransplant opportunity. Outcomes of pancreas retransplantation in earlier eras were remarkable for lower patient and pancreas graft survival for SPK retransplants, in contrast to equivalent outcomes after solitary pancreas retransplants according to single center and registry analyses.15,24 As experience has increased, recent reports from experienced single centers show that pancreas retransplantation is associated with equivalent rates of technical failure and patient survival compared to primary transplantation, although these results are likely affected by significant selection bias.4,22,25 Importantly, it has been shown that pancreas retransplantation does not decrease kidney function or allograft survival.11,15,25
Recipient evaluation The evaluation for candidacy for pancreas retransplant is similar to that for primary pancreatic transplantation, but with special attention to two key factors. First, the candidate’s glomerular filtration rate (GFR) should be reviewed in order to assess whether the higher trough levels of a calcineurin inhibitor (CNI) targeted during the early posttransplant period will be tolerated or exacerbate underlying renal dysfunction and place the patient at increased risk for end-stage renal failure. The minimum acceptable
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Recipient evaluation
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FIG. 3 Pancreas retransplant cases organized by type of primary pancreas transplant, for pancreas retransplants done in the United States between January 1, 2013 and December 31, 2017. As reported by the International Pancreas Transplant Registry (IPTR). PAK, pancreas after kidney; PTA, pancreas transplant alone; and SPK, simultaneous pancreas kidney.
pretransplant GFR is somewhat controversial, as there are few reports in the literature and the GFR range is wide.26,27 The decision to accept a particular GFR is multifaceted and includes whether the current GFR is in the context of ongoing CNI therapy, the stability of GFR over time, level of proteinuria, whether there is a living kidney donor available should the patient progress to require renal replacement therapy and the degree to which a pancreas retransplant may represent a near-term survival advantage. For candidates currently on CNI-based immunosuppression, a lower GFR (i.e., 40 mL/min) may be acceptable. In contrast, a repeat PTA candidate should ideally have a higher GFR reserve (i.e., 60 mL/min) or demonstrate that a trial of CNI does not unduly compromise the GFR. Secondly, the technical aspects of the operation necessitate a critical review of available vascular targets, typically via computerized tomography (CT) angiography (or plain CT or magnetic resonance angiography if contrast is not advised) and comfort with an array of surgical techniques for reconstruction.28 Detailed imaging of the abdominal and pelvic vascular should be obtained in order to identify problem areas and potential anastomotic sites for the planned pancreas retransplant as well as a current or future kidney transplant if needed. Pancreatic retransplantation is associated with a longer operative time and more technical complications when compared with primary transplantation, especially when the retransplant type is SPK (or PAK after prior SPK).22,25 The operating time can be impacted by
several factors. Retransplant candidates are more likely to be sensitized, the degree to which may necessitate importing the organ with sometimes challenging logistics. Extended cold ischemic times can be reduced by utilizing the virtual crossmatch, performing a predonation crossmatch on shipped blood, or by planning a charter flight in lieu of depending on commercial airline schedules for organ transport.18,29,30 In addition, adhesiolysis is generally required and it is not uncommon that a pancreatectomy of the failed allograft is indicated, or that additional exploration or a jump graft is required in order to develop a suitable site for the retransplant.22,25 At the evaluation, one should actively seek out issues of advanced peripheral vascular disease, limited venous or arterial targets, and candidates with ongoing needs for chronic anticoagulation, which may increase the risk of medical and surgical complications enough to tip the balance out of favor for a logistically complicated organ offer, or for retransplantation altogether. The patient’s overall cardiovascular, renal, and functional status must be sufficient to withstand such complications. In reports detailing reasons for exclusion from retransplant, it is notable that almost 50% of patients with late allograft failure were candidates for retransplantation. The most common reasons cited for patients being declined for a pancreas retransplant opportunity were: noncompliance, home city remote from a pancreas center, obesity/insulin resistance, personal choice, cardiovascular disease, active infection, cancer, and deconditioning.11,25
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Donor selection Donor selection for pancreas retransplant candidates should be conservative for quality, and certainly avoid predictably long preservation times, as well as older donors due to the associated increased incidence of graft thrombosis. Donor pancreas procurement for retransplants should ideally be done by an experienced pancreatic procurement surgeon who can provide a reliable assessment of pancreatic graft quality, avoid procurement injuries, and appreciate the issues of pancreas retransplant. Procuring extra donor vessels such as the carotid or femoral arteries (including their bifurcations) can salvage situations when the extra arterial conduit is required or when the iliac Y-graft is found to be damaged, diseased, or unavailable. Donor operations requiring multiple intra-abdominal procurement teams can be difficult to ensure a no-touch technique during pancreas dissection and adequate vein length (especially in combination with isolated intestinal procurement). The general avoidance of donors with an open abdomen, known intra-abdominal contamination, trauma splenectomy, or history of complex abdominal surgery is standard practice in the evaluation of potential pancreas donors, and even more important for donors intended for retransplants because of the associated increased risk of recipient intra-abdominal infection and graft pancreatitis.31
Timing Pancreas retransplant procedures have been subclassified as either early or late because the causes for primary graft failure differ and as such, confer different risks for the retransplant operation. Early retransplants are often associated with technical failures in the very early postoperative period, the majority due to thrombosis (venous ≫ arterial), pancreatitis, or bleeding that necessitates graft removal.32 The so-called pancreas switch operation (simultaneous primary graft pancreatectomy and second graft retransplant) was initially reported as a successful multicenter case series.7 Subsequent small case series were associated with inferior outcomes but results improved over time.10,33–35 If after the explant a suitable second pancreas graft is not immediately available, then there is a short window (about 2 weeks) during which a retransplant can be considered before wound healing and visceral/vascular adhesions become treacherous. The benefit of early retransplantation is conferred by the ability to make use of the same induction immunosuppression and vascular footprint before adhesion formation becomes prohibitive. In addition, the risk of sensitization is much lower, which may improve the chances for retransplantation. Returning to the waitlist without an immediate retransplant may also be
a ssociated with significant anxiety about the next transplant experience. The risks of immediate retransplantation include deep and superficial surgical site infection and the nutritional compromise/deconditioning that can occur with two or three laparotomies in rapid succession. In summary, it is quite unusual to lose a second allograft to repeat thrombosis, so these types of retransplants generally do well, and overall outcomes are comparable to those achieved with primary transplants.11,14 Outcomes after late pancreas transplant are more likely to be impacted by increased technical challenges, more surgical complications, with a trend toward more relaparotomies and infections compared to primary transplants, although 1-year patient an unadjusted graft survival were equal to primary transplants.25 In contrast, outcomes of PAK retransplantation were similar to primary transplantation, and not associated with increases in complications.15 Technical failure rates for repeat pancreas transplants (including second, third, and fourth transplants) were not different from first transplants. The 1- and 5-year death-censored graft survival rates associated with second and third pancreas retransplants was about 15% lower than those of primary transplants, which was statistically significant. Importantly, there were no significant differences in rates of technical failure or death-censored graft survival when comparing second vs third pancreas transplants.4 These single-center reports from experienced centers all show that retransplantation is associated with overall reasonable outcomes, in stark contrast to a registry report that excluded early retransplants and was limited by missing data.36
Surgical approaches The surgical approach to pancreatic retransplantation depends on characteristics of the recipient abdomen, burden of native arterial disease, available vascular targets for anastomosis, and the potential need for failed graft pancreatectomy. For early retransplants it is important to exclude infection in the reoperative field; even if no infection is apparent, it is prudent to submit a gram stain and bacterial and fungal cultures. In the event a subclinical infection is detected, targeted antimicrobial coverage can be given to decrease the risk of abscess and subsequent graft loss from technical failure.7,31 For early retransplants and selected difficult retransplants, sometimes the prior graft inflow or outflow vessels can be used for anastomosis if vascular control of the recipient iliac vasculature cannot be safely developed. Imperative to the success of late pancreas retransplant is the ability to comfortably utilize multiple techniques for pancreatic transplant (portal vs systemic venous drainage, arterial conduits, and enteric vs bladder exocrine drainage) as dictated by intraoperative
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References
findings and flexible decision-making.2,37 A historical technique utilizing a retroperitoneal approach in the iliac fossa may be tempting if there is a history of significant abdominal surgery in combination with pristine target vessels, but this approach is associated with issues related to pancreatitis, even if the graft is partially intraperitonealized. If this choice is utilized, bladder drainage of exocrine secretions may be an optimal approach to avoid difficulties with the duodenal anastomosis and avoid enteric leak or reflux pancreatitis due to occult distal partial obstruction. A transabdominal technique for retroperitoneal placement of a pancreas transplant which utilizes the native duodenum for exocrine drainage has received some recent attention.38–40 This approach could also be useful in the retransplant setting to avoid redissection of either prior vascular targets or lysis of extensive small bowel adhesions. While complete lysis of adhesions has long been the standard approach, it is accompanied by the increased risk of adhesive bowel obstruction and intra-abdominal fluid collections, therefore judicious compromise can be advantageous.
Postoperative care
the potential for graft salvage after partial thrombosis, however even after graft salvage, good long-term graft function is rare.41–44 If the decision is made to explant a graft assessed as marginally salvageable during exploration, the operative field is less likely to be contaminated and an immediate retransplant option can be quite successful.2,7
Summary Pancreas retransplantation in the modern era at experienced centers can offer comparable patient survival and acceptable graft survival rates, especially for those who experienced technical failure of their primary pancreas transplant. Retransplantation is well recognized to be associated with statistically significantly increased rejection rates and decreased mid-term graft survival when compared to outcomes of primary pancreas transplantation. For the individual retransplant candidate, a thorough discussion of the risks and benefits are essential to providing patient-centered care.
References
The postoperative care of a pancreas retransplant recipient is mostly similar to that of a primary transplant, however, nuances are centered around the recognized increased risks of rejection, infection, and graft thrombosis (as most early technical failures of primary grafts are related to thrombotic events). Therefore, the use of antilymphocyte antibody depletion and antiplatelet therapy is recommended, and a liberal use of pancreas biopsies to evaluate graft dysfunction is warranted. In the case of prior graft thrombosis, even if the etiology is not able to be discretely diagnosed, the previously used anticoagulation protocol should be amplified during the perioperative period of the retransplant. The intensity with which the anticoagulation is increased should be balanced against the risk of bleeding, which somewhat correlates with the extent of dissection or baseline (preoperative) anticoagulation. Nonetheless, it is important to err on the side of bleeding as it is remediable. Early washout for mild hemorrhage, unexplained fever, or leukocytosis should be entertained without penalty since a washout operation allows for culture and wide drainage of any collections, and often helps to resolve ileus from inflammation even if cultures are negative. This aggressive approach decreases morbidity and rate of subacute early technical graft failures. If an anamnestic rejection is a concern, then core biopsy under direct vision is safe and can help diagnose an early rejection, which without treatment would surely result in early graft loss. Very early diagnosis of graft dysfunction is paramount to
1. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery. 1967;61(6):827–837. 2. Dunn TB, Sutherland DER. Repeat pancreas transplant procedures: recipient selection and surgical techniques. Curr Transplant Rep. 2014;1(2):119–123. 3. Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2016 annual data report: pancreas. Am J Transplant. 2018;18(suppl 1): 114–171. 4. Rudolph EN, Finger EB, Chandolias N, Kandaswamy R, Sutherland DE, Dunn TB. Outcomes of pancreas retransplantation. Transplantation. 2015;99(2):367–374. 5. Sutherland DE, Goetz FC, Elick BA, Najarian JS. Experience with 49 segmental pancreas transplants in 45 diabetic patients. Transplantation. 1982;34(6):330–338. 6. Morel P, Schlumpf R, Dunn DL, Moudry-Munns K, Najarian JS, Sutherland DE. Pancreas retransplants compared with primary transplants. Transplantation. 1991;51(4):825–833. 7. Boudreaux JP, Corry RJ, Dickerman R, Sutherland DE. Combined experience with immediate pancreas retransplantation. Transplant Proc. 1991;23(1 Pt 2):1628–1629. 8. Stratta RJ, Lowell JA, Sudan D, Jerius JT. Retransplantation in the diabetic patient with a pancreas allograft. Am J Surg. 1997;174(6):759–762 [discussion 763]. 9. Stratta RJ, Taylor RJ, Sudan D, Sindhi R, Castaldo P. Experience with pancreas retransplantation. Transplant Proc. 1995;27(6):3020–3021. 10. Sansalone CV, Aseni P, Follini ML, et al. Early pancreas retransplantation for vascular thrombosis in simultaneous pancreas- kidney transplants. Transplant Proc. 1998;30(2):253–254. 11. Buron F, Thaunat O, Demuylder-Mischler S, et al. Pancreas retransplantation: a second chance for diabetic patients? Transplantation. 2013;95(2):347–352. 12. Magee JC, Barr ML, Basadonna GP, et al. Repeat organ transplantation in the United States, 1996–2005. Am J Transplant. 2007;7 (5 Pt 2):1424–1433.
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13. Humar A, Kandaswamy R, Drangstveit MB, Parr E, Gruessner AG, Sutherland DE. Surgical risks and outcome of pancreas retransplants. Surgery. 2000;127(6):634–640. 14. Genzini T, Crescentini F, Torricelli FC, et al. Pancreas retransplantation: outcomes of 20 cases. Transplant Proc. 2006;38(6):1937–1938. 15. Seal J, Selzner M, Laurence J, et al. Outcomes of pancreas retransplantation after simultaneous kidney-pancreas transplantation are comparable to pancreas after kidney transplantation alone. Transplantation. 2015;99(3):623–628. 16. Sutherland DE, Gruessner RW, Dunn DL, et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001;233(4):463–501. 17. Nagai S, Powelson JA, Taber TE, Goble ML, Mangus RS, Fridell JA. Allograft pancreatectomy: indications and outcomes. Am J Transplant. 2015;15(9):2456–2464. 18. Eby BC, Redfield RR, Ellis TM, Leverson GE, Schenian AR, Odorico JS. Virtual HLA crossmatching as a means to safely expedite transplantation of imported pancreata. Transplantation. 2016;100(5):1103–1110. 19. Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2015 annual data report: pancreas. Am J Transplant. 2017;17(suppl 1): 117–173. 20. Kandaswamy R, Skeans MA, Gustafson SK, et al. OPTN/SRTR 2013 annual data report: pancreas. Am J Transplant. 2015;15(supp 2): 1–20. 21. Finger EB, Radosevich DM, Dunn TB, et al. A composite risk model for predicting technical failure in pancreas transplantation. Am J Transplant. 2013;13(7):1840–1849. 22. LaMattina JC, Sollinger HW, Becker YT, Mezrich JD, Pirsch JD, Odorico JS. Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients. Clin Transplant. 2012;26(3):495–501. 23. Reddy KS, Shokouh-Amiri H, Stratta RJ, Gaber AO. Successful reuse of portal-enteric technique in pancreas retransplantation. Transplantation. 2000;69(11):2443–2445. 24. Terasaki Foundation Laboratory. Pancreas Transplant Outcomes for United States and Non United States Cases as Reported to the United Network for Organ Sharing and the International Pancreas Transplant Registry as of December 2011. Terasaki Foundation Laboratory; 2012:23–40. 25. Fridell JA, Mangus RS, Chen JM, et al. Late pancreas retransplantation. Clin Transplant. 2015;29(1):1–8. 26. Browne S, Gill J, Dong J, et al. The impact of pancreas transplantation on kidney allograft survival. Am J Transplant. 2011;11(9):1951–1958. 27. Pavlakis M, Khwaja K, Mandelbrot D, et al. Renal allograft failure predictors after PAK transplantation: results from the New England collaborative Association of Pancreas Programs. Transplantation. 2010;89(11):1347–1353. 28. Fridell JA, Gage E, Goggins WC, Powelson JA. Complex arterial reconstruction for pancreas transplantation in recipients with advanced arteriosclerosis. Transplantation. 2007;83(10):1385–1388.
29. Finger EB, Radosevich DM, Bland BJ, et al. Comparison of recipient outcomes following transplant from local versus imported pancreas donors. Am J Transplant. 2012;12(2):447–457. 30. Fridell JA, Mangus RS, Hollinger EF, et al. No difference in transplant outcomes for local and import pancreas allografts. Transplantation. 2009;88(5):723–728. 31. Benedetti E, Troppmann C, Gruessner AC, Sutherland DE, Dunn DL, Gruessner WG. Pancreas graft loss caused by intra- abdominal infection. A risk factor for a subsequent pancreas retransplantation. Arch Surg. 1996;131(10):1054–1060. 32. Farney AC, Rogers J, Stratta RJ. Pancreas graft thrombosis: causes, prevention, diagnosis, and intervention. Curr Opin Organ Transplant. 2012;17(1):87–92. 33. Sansalone CV, Maione G, Rossetti O, et al. Pancreas retransplantation: ideal timing and early and late results. Transplant Proc. 2006;38(4):1153–1155. 34. Hollinger EF, Powelson JA, Mangus RS, et al. Immediate retransplantation for pancreas allograft thrombosis. Am J Transplant. 2009;9(4):740–745. 35. Paraskevas SGA, Kandaswamy R, Humar A, Sutherland DER, Gruessner RWG. Pancreas exchange (PEx): single procedure graft pancreatectomy and retransplant for early graft thrombosis. Acta Chir Austriaca. 2001;33(174):2. 36. Siskind E, Maloney C, Jayaschandaran V, et al. Pancreatic retransplantation is associated with poor allograft survival: an update of the united network for organ sharing database. Pancreas. 2015;44(5):769–772. 37. Garcia-Roca R, Humar A, Sturdevant M, et al. Orthotopic placement of a segmental pancreas graft for transplant: a case report. Clin Transplant. 2010;24(3):424–428. 38. Perosa M, Noujaim H, Ianhez LE, et al. Experience with 53 portal-duodenal drained solitary pancreas transplants. Clin Transplant. 2014;28(2):198–204. 39. Boggi U, Amorese G, Marchetti P. Surgical techniques for pancreas transplantation. Curr Opin Organ Transplant. 2010;15(1):102–111. 40. Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation. Clin Transplant. 2012;26(4):550–557. 41. Douzdjian V, Abecassis MM, Cooper JL, Argibay PF, Smith JL, Corry RJ. Pancreas transplant salvage after acute venous thrombosis. Transplantation. 1993;56(1):222–223. 42. Stockland AH, Willingham DL, Paz-Fumagalli R, et al. Pancreas transplant venous thrombosis: role of endovascular interventions for graft salvage. Cardiovasc Intervent Radiol. 2009;32(2):279–283. 43. Ciancio G, Cespedes M, Olson L, Miller J, Burke GW. Partial venous thrombosis of the pancreatic allografts after simultaneous pancreas-kidney transplantation. Clin Transplant. 2000;14(5):464–471. 44. Fridell JA, Mangus RS, Mull AB, et al. Early reexploration for suspected thrombosis after pancreas transplantation. Transplantation. 2011;91(8):902–907.
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27 Pancreas retransplantation Ty B. Dunn*, Karthik V. Ramanathan† *University of Pennsylvania, Philadephia, PA, USA †Department of Surgery, University of Minnesota, Minneapolis, MN, United States O U T L I N E Introduction
339
Timing
344
Historical perspective
339
Surgical approaches
344
Indications and considerations
340
Postoperative care
345
Retransplant type and outcomes
341
Summary
345
Recipient evaluation
342
References
345
Donor selection
344
Introduction
Historical perspective
Successful pancreas transplantation continues to be the only treatment for insulin-dependent diabetes that durably restores euglycemia and metabolic control. The return of euglycemia and freedom from constant monitoring and multiple daily insulin injections or wearing a pump/monitor can significantly improve quality of life, stop the progression of diabetic complications, and in some cases is a life-saving procedure. Failure of a pancreas transplant reexposes the patient to their chronic disease state and its associated problems of dysglycemia, which can be physically and emotionally devastating. Since pancreas retransplantation is infrequently performed, few transplant centers or surgeons have substantive experience with the procedure which is currently now offered at a decreasing number of centers. This chapter outlines the history and outcomes of pancreas retransplant, key concerns in the evaluation of the retransplant candidate, surgical considerations, and an overview of the nuances of the different types and risks of pancreas retransplantion.
It was not until 12 years after the world’s first pancreas transplant was performed in 1966 that the first pancreas retransplant was accomplished.1,2 In the United States (US), the number of pancreas retransplant operations increased in parallel with that of primary pancreas transplantation and peaked in 2004 at 130 (8.8% of all pancreas transplants that year) and has since decreased to 44 (4.3% of all pancreas transplants) in 2016 [based on Organ Procurement and Transplantation Network (OPTN) data as of April 20, 2018] (Fig. 1). In contrast, about 11% of the pancreas transplant waitlist is comprised of candidates awaiting retransplantation.3 The overall number of retransplant cases performed outside the United States is comparatively lower and in decreased proportion to primary pancreas transplants, but incomplete reporting limits a more granular review of retransplant activity outside the United States [A. Gruessner ([email protected]), e-mail July 30, 2018]. According to OPTN data collected since 1988, a total of 184 transplant centers in the United States at some time or
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27. Pancreas retransplantation
Pancreas transplantation in the United States 1800 1600 1400 1200 1000 800 600 400 200 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
0
Primary transplant
Retransplant
FIG. 1 Primary and repeat pancreas transplant activity in the United States.
another have performed a pancreas transplant. Of these centers, 74% have reported doing some type of pancreas retransplant (solitary pancreas or in combination with kidney). Of these, only 24 centers (13%) have performed 20 or more retransplants of any type. Contemporary activity (the 10 years spanning 2007–2016) reveals just 14 centers (located in 7 of the 11 UNOS regions) performed 10 or more retransplants during those 10 years. Of the 120 pancreas transplant centers that were active in the year 2016, 24 centers performed a retransplant, and only half4 of these 24 centers (10% of active centers) did more than one retransplant, highlighting the relative infrequency of the procedure. The increased complexity of pancreas retransplantation, in tandem with its low frequency, makes it difficult for a center (as well as an individual surgeon) to maintain currency and provide trainees adequate exposure to this relatively rare operation. In the 20 years after the first pancreas retransplant was performed, small series of pancreas retransplants were published from the most active centers. Collectively, these reports demonstrated the feasibility of pancreas retransplantation and showed that clinical outcomes were not far below those of contemporaneous primary pancreas transplants.5–10 During this same period, pancreas transplantation as a whole was remarkable for very high surgical complication rates and 1-year graft survival below those of other solid organ transplants. However, improvements in donor selection and organ procurement, technical aspects of pancreas transplantation, and medical management of the recipient all have contributed to the significantly enhanced outcomes we expect today. With the field further maturing over the subsequent 20 years [with the routine use of induction immunosuppression, calcineurin inhibitors (CNI), valganciclovir, and modern histocompatibility techniques], improvements in outcomes of pancreatic
retransplantation have continued to be congruent with those seen in contemporaneous primary transplantation. Compared to primary transplants, outcomes of pancreas retransplantation in the modern era are notable for a similar risk of technical failure, and only slightly decreased 1-year graft survival rates. Longer term graft survival is significantly decreased for cases of pancreas retransplant compared to primary transplant, which is consistent with all other deceased donor solid organ transplant types.4,11,12 Patient survival after pancreas retransplantation in the modern era is excellent and not significantly different from that seen after primary transplantation.4,11 Results of the largest series of pancreas retransplants are summarized in Table 1.4,6,8,9,11,13–16 Because the overall outcomes of primary pancreas transplantation have improved over time, the age of the typical pancreas transplant candidate has increased, and medical management of diabetes has improved, it is not surprising that pancreas retransplants are becoming less common. In tandem, patient survival for all types of primary pancreas transplant continues to increase.3 It is important to recognize that a significant number of patients with a failed pancreas transplant may benefit from retransplantation. One-year patient and graft survival rates for repeat pancreas transplants are near those of primary transplant. Some patients will be best served by an opportunity for retransplantation, especially when they require kidney retransplantation or remain on immunosuppression with a well-functioning kidney transplant.
Indications and considerations Diabetics who suffer from severe hypoglycemic episodes or progression of microvascular complications
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Retransplant type and outcomes
TABLE 1 Summary of studies reporting 20 or more pancreas retransplants Author Year
Center
Years
N
Type
TF
1 Yr AR
1 Yr GS
1 Yr PS
FU
Buron 2013
Lyon Geneva 1976–2008
37
70% PAK 27% SPK 3% PTA
16 (43%)
NR
64%
100%
7.8 yr
Morel 1991
U Minn
1978–1989
68
35% PAK 18% SPK 47% PTA
16 (24%)
57%
43%
89%
NR
Humar 2000 U Minn
1994–1997
26
46% PAK 35% SPK 19% PTA
7 (27%)
55%
69%
96%
NR
Sutherland 2001#
U Minn
1978–2000
191
49% PAK 19% SPK 32% PTA
NR
NR
51% 64% 45%
88% 83% 90%
NR
Rudolph 2015#
U Minn
1978–2012
415 (included 3rd and 4th Tx)
48% PAK 21% SPK 30% PTA
66 (16%)
28%
76%
88%
NR
Genzini 2006 Sao Paulo
1996–2005
20
NR
2 (10%)
NR
85%
95%
2 yr
Rudolph 2015*
U Minn
2003–2012
155 (including 3rd and 4th Tx)
57% PAK 14% SPK 29% PTA
17 (11%)
34%
81%
90%
4.7 yr PAK 4.6 yr SPK 4.3 yr PTA
Rudolph 2015*
U Minn
2003–2012
125 (restricted to 2nd Tx)
56% PAK 14% SPK 30% PTA
14 (11%)
35%
73%
96%
4 yr PAK 4.8 yr SPK 3.5 yr PTA
Fridell 2015
U Indiana
2003–2013
20
65% PAK 25% SPK 10% PTA
0 (0%)
5%
90%
95%
4.6
TF, technical failure; AR, acute rejection; GS, graft survival; PS, patient survival; FU, mean follow-up; NR, not reported. The symbol # indicates that the publication includes previously published cases, and * denotes a subanalysis of a modern retransplant cohort.
typically have a significant chronic disease burden and come to transplant evaluation after other less invasive therapies fail. The indications for pancreas retransplantation are the same as for primary transplants, with special consideration of a few characteristics that are of particular importance to retransplantation—that of a vetted ability to adhere to the requisite posttransplant medication and follow-up protocols, sufficient cardiopulmonary reserve to withstand a major operation, and the availability of surgical targets suitable for anastomosis. It is important to avoid increased immunologic risk grafts (positive crossmatch or with donors to whom the candidate has a significant amount of donor-specific anti HLA antibody). Of course, these characteristics are also important for primary transplants but carry special weight when considering a retransplant opportunity. For the individual candidate, factors that contributed to the technical failure of a primary allograft must be sought and corrected (or mitigated) during the pre-, peri-, and postoperative phases of the retransplant. In the case of early graft failure due to thrombosis, a comprehensive thrombophilia evaluation should be done and a plan for
anticoagulation at retransplant established. Graft failures due to pancreatitis require a more conservative approach to donor selection and the predicted cold ischemic time. Candidates who experience late graft failures or allograft pancreatectomy may become sensitized to HLA, which may decrease the likelihood of finding a match for retransplantation.17 For these candidates, being open to importing the graft from regional or national donor service areas, in combination with using a virtual crossmatch approach or shipping blood for crossmatching prior to final organ allocation may be highly productive.18 Even with a negative crossmatch, retransplantation has been associated with a significantly increased risk of early and mid-term immunologic graft loss.4
Retransplant type and outcomes Currently, the most common type of pancreas retransplant is PAK, which represents over 50% of all pancreas retransplants.3, 19 While about 2% of SPKs have been consistently classified as pancreas retransplants, over the
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FIG. 2 Pancreas retransplant frequency (Panel A) and proportion of overall transplants of that type (Panel B) by year in the United States, as reported by the International Pancreas Transplant Registry (IPTR). PAK, pancreas after kidney; PTA, pancreas transplant alone; and SPK, simultaneous pancreas kidney.
past several years PAK retransplants have increased and now comprise over 30% of all PAK cases (Fig. 2A and B). Importantly, there has not been an increase in SPK retransplants since the new allocation system went into effect.20 The PAK retransplant cases are most commonly performed after a primary SPK or PAK transplant type, and repeat SPKs are typically performed after a primary SPK (Fig. 3). Pancreas transplant alone (PTA) recipients have the highest risk of rejection but may benefit from retransplantation, in particular, if the first graft was lost to technical failure. Recipients of PTA are disproportionately more female and younger than other types of pancreas recipients and do not have ESRD, all of which are key factors that
likely contribute to the highest observed rates of posttransplant patient survival. Technical failure of the pancreas allograft (within the first 90 days posttransplant), while slightly decreased over time, continue to affect about 10% of solitary pancreas transplants (PTA and PAK), in contrast to about 5% of SPKs; avoidance of multiple risk factors is key to minimizing this devastating outcome.20,21 Surgical and immunologic risks are increased for the pancreas retransplant candidate. An SPK retransplant is more technically challenging since about 75% of recipients undergo removal of the failed primary allograft either before or during the retransplant operation.22 Incidental procedures such as appendectomy, lysis of adhesions, and herniorrhaphy are also not infrequently performed during retransplantation. The anatomy after pancreatectomy often dictates alternate surgical techniques such as creation of a Rouxen-Y bowel anastomosis or placement of the graft higher (on the inferior vena cava) or lower (external iliac artery) or on the left iliac system for systemically drained grafts, although portal venous drainage technique is an option for dealing with hostile iliac veins and has even been successfully reused.23 Candidates for retransplantation are more likely to be highly sensitized, which, together with the lower frequency of deceased donors suitable for pancreas donation compared to kidney donation, can make wait times longer for a retransplant opportunity. Outcomes of pancreas retransplantation in earlier eras were remarkable for lower patient and pancreas graft survival for SPK retransplants, in contrast to equivalent outcomes after solitary pancreas retransplants according to single center and registry analyses.15,24 As experience has increased, recent reports from experienced single centers show that pancreas retransplantation is associated with equivalent rates of technical failure and patient survival compared to primary transplantation, although these results are likely affected by significant selection bias.4,22,25 Importantly, it has been shown that pancreas retransplantation does not decrease kidney function or allograft survival.11,15,25
Recipient evaluation The evaluation for candidacy for pancreas retransplant is similar to that for primary pancreatic transplantation, but with special attention to two key factors. First, the candidate’s glomerular filtration rate (GFR) should be reviewed in order to assess whether the higher trough levels of a calcineurin inhibitor (CNI) targeted during the early posttransplant period will be tolerated or exacerbate underlying renal dysfunction and place the patient at increased risk for end-stage renal failure. The minimum acceptable
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FIG. 3 Pancreas retransplant cases organized by type of primary pancreas transplant, for pancreas retransplants done in the United States between January 1, 2013 and December 31, 2017. As reported by the International Pancreas Transplant Registry (IPTR). PAK, pancreas after kidney; PTA, pancreas transplant alone; and SPK, simultaneous pancreas kidney.
pretransplant GFR is somewhat controversial, as there are few reports in the literature and the GFR range is wide.26,27 The decision to accept a particular GFR is multifaceted and includes whether the current GFR is in the context of ongoing CNI therapy, the stability of GFR over time, level of proteinuria, whether there is a living kidney donor available should the patient progress to require renal replacement therapy and the degree to which a pancreas retransplant may represent a near-term survival advantage. For candidates currently on CNI-based immunosuppression, a lower GFR (i.e., 40 mL/min) may be acceptable. In contrast, a repeat PTA candidate should ideally have a higher GFR reserve (i.e., 60 mL/min) or demonstrate that a trial of CNI does not unduly compromise the GFR. Secondly, the technical aspects of the operation necessitate a critical review of available vascular targets, typically via computerized tomography (CT) angiography (or plain CT or magnetic resonance angiography if contrast is not advised) and comfort with an array of surgical techniques for reconstruction.28 Detailed imaging of the abdominal and pelvic vascular should be obtained in order to identify problem areas and potential anastomotic sites for the planned pancreas retransplant as well as a current or future kidney transplant if needed. Pancreatic retransplantation is associated with a longer operative time and more technical complications when compared with primary transplantation, especially when the retransplant type is SPK (or PAK after prior SPK).22,25 The operating time can be impacted by
several factors. Retransplant candidates are more likely to be sensitized, the degree to which may necessitate importing the organ with sometimes challenging logistics. Extended cold ischemic times can be reduced by utilizing the virtual crossmatch, performing a predonation crossmatch on shipped blood, or by planning a charter flight in lieu of depending on commercial airline schedules for organ transport.18,29,30 In addition, adhesiolysis is generally required and it is not uncommon that a pancreatectomy of the failed allograft is indicated, or that additional exploration or a jump graft is required in order to develop a suitable site for the retransplant.22,25 At the evaluation, one should actively seek out issues of advanced peripheral vascular disease, limited venous or arterial targets, and candidates with ongoing needs for chronic anticoagulation, which may increase the risk of medical and surgical complications enough to tip the balance out of favor for a logistically complicated organ offer, or for retransplantation altogether. The patient’s overall cardiovascular, renal, and functional status must be sufficient to withstand such complications. In reports detailing reasons for exclusion from retransplant, it is notable that almost 50% of patients with late allograft failure were candidates for retransplantation. The most common reasons cited for patients being declined for a pancreas retransplant opportunity were: noncompliance, home city remote from a pancreas center, obesity/insulin resistance, personal choice, cardiovascular disease, active infection, cancer, and deconditioning.11,25
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Donor selection Donor selection for pancreas retransplant candidates should be conservative for quality, and certainly avoid predictably long preservation times, as well as older donors due to the associated increased incidence of graft thrombosis. Donor pancreas procurement for retransplants should ideally be done by an experienced pancreatic procurement surgeon who can provide a reliable assessment of pancreatic graft quality, avoid procurement injuries, and appreciate the issues of pancreas retransplant. Procuring extra donor vessels such as the carotid or femoral arteries (including their bifurcations) can salvage situations when the extra arterial conduit is required or when the iliac Y-graft is found to be damaged, diseased, or unavailable. Donor operations requiring multiple intra-abdominal procurement teams can be difficult to ensure a no-touch technique during pancreas dissection and adequate vein length (especially in combination with isolated intestinal procurement). The general avoidance of donors with an open abdomen, known intra-abdominal contamination, trauma splenectomy, or history of complex abdominal surgery is standard practice in the evaluation of potential pancreas donors, and even more important for donors intended for retransplants because of the associated increased risk of recipient intra-abdominal infection and graft pancreatitis.31
Timing Pancreas retransplant procedures have been subclassified as either early or late because the causes for primary graft failure differ and as such, confer different risks for the retransplant operation. Early retransplants are often associated with technical failures in the very early postoperative period, the majority due to thrombosis (venous ≫ arterial), pancreatitis, or bleeding that necessitates graft removal.32 The so-called pancreas switch operation (simultaneous primary graft pancreatectomy and second graft retransplant) was initially reported as a successful multicenter case series.7 Subsequent small case series were associated with inferior outcomes but results improved over time.10,33–35 If after the explant a suitable second pancreas graft is not immediately available, then there is a short window (about 2 weeks) during which a retransplant can be considered before wound healing and visceral/vascular adhesions become treacherous. The benefit of early retransplantation is conferred by the ability to make use of the same induction immunosuppression and vascular footprint before adhesion formation becomes prohibitive. In addition, the risk of sensitization is much lower, which may improve the chances for retransplantation. Returning to the waitlist without an immediate retransplant may also be
a ssociated with significant anxiety about the next transplant experience. The risks of immediate retransplantation include deep and superficial surgical site infection and the nutritional compromise/deconditioning that can occur with two or three laparotomies in rapid succession. In summary, it is quite unusual to lose a second allograft to repeat thrombosis, so these types of retransplants generally do well, and overall outcomes are comparable to those achieved with primary transplants.11,14 Outcomes after late pancreas transplant are more likely to be impacted by increased technical challenges, more surgical complications, with a trend toward more relaparotomies and infections compared to primary transplants, although 1-year patient an unadjusted graft survival were equal to primary transplants.25 In contrast, outcomes of PAK retransplantation were similar to primary transplantation, and not associated with increases in complications.15 Technical failure rates for repeat pancreas transplants (including second, third, and fourth transplants) were not different from first transplants. The 1- and 5-year death-censored graft survival rates associated with second and third pancreas retransplants was about 15% lower than those of primary transplants, which was statistically significant. Importantly, there were no significant differences in rates of technical failure or death-censored graft survival when comparing second vs third pancreas transplants.4 These single-center reports from experienced centers all show that retransplantation is associated with overall reasonable outcomes, in stark contrast to a registry report that excluded early retransplants and was limited by missing data.36
Surgical approaches The surgical approach to pancreatic retransplantation depends on characteristics of the recipient abdomen, burden of native arterial disease, available vascular targets for anastomosis, and the potential need for failed graft pancreatectomy. For early retransplants it is important to exclude infection in the reoperative field; even if no infection is apparent, it is prudent to submit a gram stain and bacterial and fungal cultures. In the event a subclinical infection is detected, targeted antimicrobial coverage can be given to decrease the risk of abscess and subsequent graft loss from technical failure.7,31 For early retransplants and selected difficult retransplants, sometimes the prior graft inflow or outflow vessels can be used for anastomosis if vascular control of the recipient iliac vasculature cannot be safely developed. Imperative to the success of late pancreas retransplant is the ability to comfortably utilize multiple techniques for pancreatic transplant (portal vs systemic venous drainage, arterial conduits, and enteric vs bladder exocrine drainage) as dictated by intraoperative
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References
findings and flexible decision-making.2,37 A historical technique utilizing a retroperitoneal approach in the iliac fossa may be tempting if there is a history of significant abdominal surgery in combination with pristine target vessels, but this approach is associated with issues related to pancreatitis, even if the graft is partially intraperitonealized. If this choice is utilized, bladder drainage of exocrine secretions may be an optimal approach to avoid difficulties with the duodenal anastomosis and avoid enteric leak or reflux pancreatitis due to occult distal partial obstruction. A transabdominal technique for retroperitoneal placement of a pancreas transplant which utilizes the native duodenum for exocrine drainage has received some recent attention.38–40 This approach could also be useful in the retransplant setting to avoid redissection of either prior vascular targets or lysis of extensive small bowel adhesions. While complete lysis of adhesions has long been the standard approach, it is accompanied by the increased risk of adhesive bowel obstruction and intra-abdominal fluid collections, therefore judicious compromise can be advantageous.
Postoperative care
the potential for graft salvage after partial thrombosis, however even after graft salvage, good long-term graft function is rare.41–44 If the decision is made to explant a graft assessed as marginally salvageable during exploration, the operative field is less likely to be contaminated and an immediate retransplant option can be quite successful.2,7
Summary Pancreas retransplantation in the modern era at experienced centers can offer comparable patient survival and acceptable graft survival rates, especially for those who experienced technical failure of their primary pancreas transplant. Retransplantation is well recognized to be associated with statistically significantly increased rejection rates and decreased mid-term graft survival when compared to outcomes of primary pancreas transplantation. For the individual retransplant candidate, a thorough discussion of the risks and benefits are essential to providing patient-centered care.
References
The postoperative care of a pancreas retransplant recipient is mostly similar to that of a primary transplant, however, nuances are centered around the recognized increased risks of rejection, infection, and graft thrombosis (as most early technical failures of primary grafts are related to thrombotic events). Therefore, the use of antilymphocyte antibody depletion and antiplatelet therapy is recommended, and a liberal use of pancreas biopsies to evaluate graft dysfunction is warranted. In the case of prior graft thrombosis, even if the etiology is not able to be discretely diagnosed, the previously used anticoagulation protocol should be amplified during the perioperative period of the retransplant. The intensity with which the anticoagulation is increased should be balanced against the risk of bleeding, which somewhat correlates with the extent of dissection or baseline (preoperative) anticoagulation. Nonetheless, it is important to err on the side of bleeding as it is remediable. Early washout for mild hemorrhage, unexplained fever, or leukocytosis should be entertained without penalty since a washout operation allows for culture and wide drainage of any collections, and often helps to resolve ileus from inflammation even if cultures are negative. This aggressive approach decreases morbidity and rate of subacute early technical graft failures. If an anamnestic rejection is a concern, then core biopsy under direct vision is safe and can help diagnose an early rejection, which without treatment would surely result in early graft loss. Very early diagnosis of graft dysfunction is paramount to
1. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery. 1967;61(6):827–837. 2. Dunn TB, Sutherland DER. Repeat pancreas transplant procedures: recipient selection and surgical techniques. Curr Transplant Rep. 2014;1(2):119–123. 3. Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2016 annual data report: pancreas. Am J Transplant. 2018;18(suppl 1): 114–171. 4. Rudolph EN, Finger EB, Chandolias N, Kandaswamy R, Sutherland DE, Dunn TB. Outcomes of pancreas retransplantation. Transplantation. 2015;99(2):367–374. 5. Sutherland DE, Goetz FC, Elick BA, Najarian JS. Experience with 49 segmental pancreas transplants in 45 diabetic patients. Transplantation. 1982;34(6):330–338. 6. Morel P, Schlumpf R, Dunn DL, Moudry-Munns K, Najarian JS, Sutherland DE. Pancreas retransplants compared with primary transplants. Transplantation. 1991;51(4):825–833. 7. Boudreaux JP, Corry RJ, Dickerman R, Sutherland DE. Combined experience with immediate pancreas retransplantation. Transplant Proc. 1991;23(1 Pt 2):1628–1629. 8. Stratta RJ, Lowell JA, Sudan D, Jerius JT. Retransplantation in the diabetic patient with a pancreas allograft. Am J Surg. 1997;174(6):759–762 [discussion 763]. 9. Stratta RJ, Taylor RJ, Sudan D, Sindhi R, Castaldo P. Experience with pancreas retransplantation. Transplant Proc. 1995;27(6):3020–3021. 10. Sansalone CV, Aseni P, Follini ML, et al. Early pancreas retransplantation for vascular thrombosis in simultaneous pancreas- kidney transplants. Transplant Proc. 1998;30(2):253–254. 11. Buron F, Thaunat O, Demuylder-Mischler S, et al. Pancreas retransplantation: a second chance for diabetic patients? Transplantation. 2013;95(2):347–352. 12. Magee JC, Barr ML, Basadonna GP, et al. Repeat organ transplantation in the United States, 1996–2005. Am J Transplant. 2007;7 (5 Pt 2):1424–1433.
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13. Humar A, Kandaswamy R, Drangstveit MB, Parr E, Gruessner AG, Sutherland DE. Surgical risks and outcome of pancreas retransplants. Surgery. 2000;127(6):634–640. 14. Genzini T, Crescentini F, Torricelli FC, et al. Pancreas retransplantation: outcomes of 20 cases. Transplant Proc. 2006;38(6):1937–1938. 15. Seal J, Selzner M, Laurence J, et al. Outcomes of pancreas retransplantation after simultaneous kidney-pancreas transplantation are comparable to pancreas after kidney transplantation alone. Transplantation. 2015;99(3):623–628. 16. Sutherland DE, Gruessner RW, Dunn DL, et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001;233(4):463–501. 17. Nagai S, Powelson JA, Taber TE, Goble ML, Mangus RS, Fridell JA. Allograft pancreatectomy: indications and outcomes. Am J Transplant. 2015;15(9):2456–2464. 18. Eby BC, Redfield RR, Ellis TM, Leverson GE, Schenian AR, Odorico JS. Virtual HLA crossmatching as a means to safely expedite transplantation of imported pancreata. Transplantation. 2016;100(5):1103–1110. 19. Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2015 annual data report: pancreas. Am J Transplant. 2017;17(suppl 1): 117–173. 20. Kandaswamy R, Skeans MA, Gustafson SK, et al. OPTN/SRTR 2013 annual data report: pancreas. Am J Transplant. 2015;15(supp 2): 1–20. 21. Finger EB, Radosevich DM, Dunn TB, et al. A composite risk model for predicting technical failure in pancreas transplantation. Am J Transplant. 2013;13(7):1840–1849. 22. LaMattina JC, Sollinger HW, Becker YT, Mezrich JD, Pirsch JD, Odorico JS. Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients. Clin Transplant. 2012;26(3):495–501. 23. Reddy KS, Shokouh-Amiri H, Stratta RJ, Gaber AO. Successful reuse of portal-enteric technique in pancreas retransplantation. Transplantation. 2000;69(11):2443–2445. 24. Terasaki Foundation Laboratory. Pancreas Transplant Outcomes for United States and Non United States Cases as Reported to the United Network for Organ Sharing and the International Pancreas Transplant Registry as of December 2011. Terasaki Foundation Laboratory; 2012:23–40. 25. Fridell JA, Mangus RS, Chen JM, et al. Late pancreas retransplantation. Clin Transplant. 2015;29(1):1–8. 26. Browne S, Gill J, Dong J, et al. The impact of pancreas transplantation on kidney allograft survival. Am J Transplant. 2011;11(9):1951–1958. 27. Pavlakis M, Khwaja K, Mandelbrot D, et al. Renal allograft failure predictors after PAK transplantation: results from the New England collaborative Association of Pancreas Programs. Transplantation. 2010;89(11):1347–1353. 28. Fridell JA, Gage E, Goggins WC, Powelson JA. Complex arterial reconstruction for pancreas transplantation in recipients with advanced arteriosclerosis. Transplantation. 2007;83(10):1385–1388.
29. Finger EB, Radosevich DM, Bland BJ, et al. Comparison of recipient outcomes following transplant from local versus imported pancreas donors. Am J Transplant. 2012;12(2):447–457. 30. Fridell JA, Mangus RS, Hollinger EF, et al. No difference in transplant outcomes for local and import pancreas allografts. Transplantation. 2009;88(5):723–728. 31. Benedetti E, Troppmann C, Gruessner AC, Sutherland DE, Dunn DL, Gruessner WG. Pancreas graft loss caused by intra- abdominal infection. A risk factor for a subsequent pancreas retransplantation. Arch Surg. 1996;131(10):1054–1060. 32. Farney AC, Rogers J, Stratta RJ. Pancreas graft thrombosis: causes, prevention, diagnosis, and intervention. Curr Opin Organ Transplant. 2012;17(1):87–92. 33. Sansalone CV, Maione G, Rossetti O, et al. Pancreas retransplantation: ideal timing and early and late results. Transplant Proc. 2006;38(4):1153–1155. 34. Hollinger EF, Powelson JA, Mangus RS, et al. Immediate retransplantation for pancreas allograft thrombosis. Am J Transplant. 2009;9(4):740–745. 35. Paraskevas SGA, Kandaswamy R, Humar A, Sutherland DER, Gruessner RWG. Pancreas exchange (PEx): single procedure graft pancreatectomy and retransplant for early graft thrombosis. Acta Chir Austriaca. 2001;33(174):2. 36. Siskind E, Maloney C, Jayaschandaran V, et al. Pancreatic retransplantation is associated with poor allograft survival: an update of the united network for organ sharing database. Pancreas. 2015;44(5):769–772. 37. Garcia-Roca R, Humar A, Sturdevant M, et al. Orthotopic placement of a segmental pancreas graft for transplant: a case report. Clin Transplant. 2010;24(3):424–428. 38. Perosa M, Noujaim H, Ianhez LE, et al. Experience with 53 portal-duodenal drained solitary pancreas transplants. Clin Transplant. 2014;28(2):198–204. 39. Boggi U, Amorese G, Marchetti P. Surgical techniques for pancreas transplantation. Curr Opin Organ Transplant. 2010;15(1):102–111. 40. Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation. Clin Transplant. 2012;26(4):550–557. 41. Douzdjian V, Abecassis MM, Cooper JL, Argibay PF, Smith JL, Corry RJ. Pancreas transplant salvage after acute venous thrombosis. Transplantation. 1993;56(1):222–223. 42. Stockland AH, Willingham DL, Paz-Fumagalli R, et al. Pancreas transplant venous thrombosis: role of endovascular interventions for graft salvage. Cardiovasc Intervent Radiol. 2009;32(2):279–283. 43. Ciancio G, Cespedes M, Olson L, Miller J, Burke GW. Partial venous thrombosis of the pancreatic allografts after simultaneous pancreas-kidney transplantation. Clin Transplant. 2000;14(5):464–471. 44. Fridell JA, Mangus RS, Mull AB, et al. Early reexploration for suspected thrombosis after pancreas transplantation. Transplantation. 2011;91(8):902–907.
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