Solid pancreas transplant: Pushing forward

Table 1 Studies comparing pancreas transplant outcomes between donations after cardiac death vs donation after brain death pancreas allograft recipients

First author/ yr	Country	Type of study	No. transplants	Mean donor age (yr)	Donor BMI [Median, IQR]	Warm ischemia time (min)	Cold ischemia time (hours)	Follow-up (yr)	Comments/conclusions
D’Alessandro et al[41], 2004	United States	Cohort	31 DCD; 455 DBD	Unclear	ns	15.3 (SD ns)	15.9 (SD ns)	5	No difference in 5-yr graft survival in SPKs
Fernandez et al[43], 2005	United States	Cohort	37 DCD; 539 DBD	31	ns	17.5 (SD = 9.9)	15.8 (SD = 3.4)	5	Indistinguishable patient and graft 5-yr survival in SPKs. Elevated DGF rate on DCD kidneys, with no significant long-term impact.
Salvalaggio et al[44], 2006	United States	Cohort; OPTN/UNOS Registry	57 DCD; 3948 DBD	DCD= 30.1; DBD = 29	ns	ns	15.7	5	For SPK recipients, the wait for DCD organs was shorter. DCD SPK recipients had longer hospital stay. Renal DGF was higher with DCD organs. Higher thrombosis rates (12.8% vs 6.1%)
Bellingham et al[42], 2011	United States	Cohort	72 DCD; 903 DBD	DCD= 30	ns	20.8 (SD = 9.4)	ns	10	No difference in surgical complications, rejection or hemoglobin A1c levels.
Muthusamy et al[45], 2012	United Kingdom	Cohort	134 DCD; 875 DBD	DBD = 32; DCD= 28	23	12	12.5	1	Similar patient and graft survival, with improved DCD pancreas graft survival if performed as an SPK. Early graft loss in the DCD cohort was mainly due to thrombosis (8% vs 4%)
Shahrestani et al[46], 2017	Australia	Systematic review and meta-analysis	762 DCD; 23609 DBD (included 10 cohort studies and 8 case reports)	DBD = 37 ns	21-25 ns	ns	ns	0.3-15	No significant difference in 10-yr graft or patient survival. Higher graft thrombosis risk with DCDs [95%CI: 1.04-2.67; P = 0.006]. Thrombosis risk not higher when DCD donors were given ante-mortem heparin (P = 0.62)
Kopp et al[39], 2018	The Netherlands	Cohort	21 DCD; 83 DBD	a	a	31 (median)	11 (median)	5	Without the DCD factor, PDRI from DCD donors was lower. Donor age was the only donor-related risk factor associated with graft survival. Post-op bleeding and renal DGF were more common with DCDs. Graft survivals were comparable. DCD pancreata had lower thrombosis incidence. DCD donors yield similar outcomes for low PDRI. Most DCD donors were younger. DCD grafts may be a better option rather than older DBD donors.

^aRange not significantly different between DCD vs DBD donors. BMI: Body mass index; SD: Standard deviation; ns: Not stated in the study; DCD: Donation after cardiac death; DBD: Donation after brain death; SPK: Simultaneous kidney-pancreas transplant; DGF: Delayed graft function; PDRI: Pancreas donor risk index.

Table 2 Studies on the effect of pancreas procurement professionalization and center volume on pancreas transplant outcomes

First author, yr	Study aim	Region, country	Study period	No. cases	Results/comments
Boer et al[49], 2017	Analysis of abdominal organ procurement quality and clinical impact.	Eurotransplant, The Netherlands	2012-2013	591 procurements	13% surgical injuries on procured pancreata, leading to 3% pancreas discards. Higher BMI, DCD donation in liver procurement were risk factors for discard due to injury. High procurement volume centers were associated with less pancreatic injury.
Lam et al[50], 2017	Analysis on the effect of the abdominal recovery team professionalization on the pancreatic procurement injury and acceptance for transplant.	Eurotransplant, The Netherlands	2002-2015	264 procurements	31.8% pancreatic surgical injuries. 85.6% of procured pancreata were eventually transplanted. Surgeons certified in abdominal organ procurements recovered more grafts from older donors, DCDs, and had less surgical injuries. Predictors to proceed with pancreas transplant were: certified procurement surgeons; surgeons from a pancreas transplant center; DBD donation; and lower donor BMI. Procurement certification results in less surgical damage and more pancreata transplanted.
Kopp et al[52], 2017	Analysis of the effect of the transplant center volume on pancreas transplant outcomes.	Eurotransplant, The Netherlands	2008-2013	1276 pancreas transplants	Centers were classified into: low (< 5 transplants/yr); medium (5-13/yr); high volume (≥ 13/yr). Patient and graft survival were superior in higher volume centers. High center volumes were protective for graft failure, even though they transplanted organs with higher PDRI.
Alhamad et al[53], 2017	Analysis of the effect of the transplant center volume on the pancreas allograft failure risk.	UNOS, United States	2000-2013	11568 SPKs and 4308 solitary pancreas transplants	Centers were categorized into low, medium, and high tertiles. Low volume centers were associated with higher pancreatic failure risk. High volume centers had better graft survival rates irrespective of PDRI.

BMI: Body mass index; DCD: Donation after cardiac death; DBD: Donation after brain death; PDRI: Pancreas donor risk index; SPKs: Simultaneous kidney-pancreas transplants.

Table 3 Studies on Simultaneous pancreas and kidney transplant outcomes of C-peptide positive vs C-peptide negative recipients

First author, yr	Country	No. patients	Study period	C-peptide positive (%)	BMI (kg/m2) Mean (SD)	Follow-up (yr)	Outcomes	Conclusion
Chakkera et al[61], 2010	United States	80	2003-2008	a15	T1DM 24.8 (4.2); T2DM 27 (3)	1	No difference in graft (kidney and pancreas) or patient survival.	SPK should be considered in selected patients with T2DM and ESRD. C-peptide measurements for ESRD patients can be misleading.
Light et al[64], 2013	United States	173	1989-2008	c33.5	T2DM 26.1 (ns)d; T1DM 22.5 (ns)d (P < 0.0001)	20	T2DM were older at diabetes diagnosis, older at transplant, and heavier pre- and post-transplant, and had better graft survival. T1DM had better patient survival	There was a difference in patient but not graft survival in 20 yr follow-up.
Stratta et al[62], 2015	United States	162	2001-2013	b18.5	T2DM 26.1 (3.3); T1DM 24.4 (3.2)	5.6 (median)	No difference in patient and graft survival or surgical complications, rejections, serum creatinine, HbA1c, eGFR, C-peptide and weight gain were higher in the C-peptide positive group.	C-peptide “positive” patients appear to have a T2DM phenotype. Outcomes were similar between the two groups, suggesting that C-peptide should not be used exclusively when assessing for SPK transplant candidacy.
Shin et al[65], 2017	Republic of Korea	217	2004-2015	ens	T2DM 38 (9); T1DM 18 (7)	5	Similar post-operative HbA1c (< 6%), fasting insulin, HOMA of insulin resistance, and insulinogenic index. Higher post-transplant C-peptide in T2DM recipients.	No significant difference in insulin resistance or β-cell function in 5 yr.

^aT2DM definition: C-peptide presence, negative glutamic acid decarboxylase antibody, no diabetic ketoacidosis, use of oral hypoglycemics;

^bC-peptide “positive” (T2DM) = C-peptide ≥ 2.0 ng/mL; C-peptide “negative” = C-peptide < 2.0 ng/mL;

^cPatients with undetectable C-peptide (< 0.8 ng/mL) were considered T1DM; patients with detectable C-peptide (> 0.8 ng/mL) were considered T2DM;

^dSD not stated;

^ePatients were classified as T1DM and T2DM, based upon the American Diabetes Association and the World Health Organization definitions of T2DM. As such, there were 151 T1DM [C-peptide 0.92 (SD = 0.58) ng/mL] and 42 T2DM [C-peptide 3.49 (SD = 3.95) ng/mL] patients. T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; HbA1c: Glycosylated hemoglobin A1; SPK: Simultaneous kidney-pancreas transplant; ns: Not stated; HOMA: Homeostasis model assessment.