The US transplantation and donation community needs COVID‐19–specific information to guide safe and effective transplant care during the pandemic. Goff et al.'s article is on page 2100.
Background Total pancreatectomy (TP) with intraportal islet autotransplantation (IAT) can relieve pain and preserve β-cell mass in patients with chronic pancreatitis (CP) when other therapies fail. ...We report on a >30-year single-center series. Study Design Four hundred and nine patients (including 53 children, 5 to 18 years) with CP underwent TP-IAT from February 1977 to September 2011 (etiology: idiopathic, 41%; Sphincter of Oddi dysfunction/biliary, 9%; genetic, 14%; divisum, 17%; alcohol, 7%; and other, 12%; mean age was 35.3 years, 74% were female; 21% has earlier operations, including 9% Puestow procedure, 6% Whipple, 7% distal pancreatectomy, and 2% other). Islet function was classified as insulin independent for those on no insulin; partial, if known C-peptide positive or euglycemic on once-daily insulin; and insulin dependent if on standard basal–bolus diabetic regimen. A 36-item Short Form (SF-36) survey for quality of life was completed by patients before and in serial follow-up since 2007, with an integrated survey that was added in 2008. Results Actuarial patient survival post TP-IAT was 96% in adults and 98% in children (1 year) and 89% and 98% (5 years). Complications requiring relaparotomy occurred in 15.9% and bleeding (9.5%) was the most common complication. IAT function was achieved in 90% (C-peptide >0.6 ng/mL). At 3 years, 30% were insulin independent (25% in adults, 55% in children) and 33% had partial function. Mean hemoglobin A1c was <7.0% in 82%. Earlier pancreas surgery lowered islet yield (2,712 vs 4,077/kg; p = 0.003). Islet yield (<2,500/kg 36%; 2,501 to 5,000/kg 39%; >5,000/kg 24%) correlated with degree of function with insulin-independent rates at 3 years of 12%, 22%, and 72%, and rates of partial function 33%, 62%, and 24%. All patients had pain before TP-IAT and nearly all were on daily narcotics. After TP-IAT, 85% had pain improvement. By 2 years, 59% had ceased narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; and 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions, including the Physical and Mental Component Summaries (p < 0.01), whether on narcotics or not. Conclusions TP can ameliorate pain and improve quality of life in otherwise refractory CP patients, even if narcotic withdrawal is delayed or incomplete because of earlier long-term use. IAT preserves meaningful islet function in most patients and substantial islet function in more than two thirds of patients, with insulin independence occurring in one quarter of adults and half the children.
Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ ...cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use "nanowarming," which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.
The recent identification of an outbreak of 2019‐ novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential ...impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.
Given the current spread of a novel coronavirus, transplant infectious disease experts discuss the impact of emerging infections on the transplant community and suggest current management strategies.
OBJECTIVE:Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT).
BACKGROUND:Chronic pancreatitis (CP) is increasingly treated by ...a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly.
METHODS:In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative “pancreatic pain” similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year.
RESULTS:In our patients, the duration (mean ± SD) of CP before their TP-IAT was 7.1 ± 0.3 years and narcotic usage of 3.3 ± 0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield—in islet equivalents (IEQ)—per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (≥5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category.
CONCLUSIONS:This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.
Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ disease. Since the advent of ...transplantation, the promise of functional replacement has attracted an exponential mismatch between organ supply and demand. Theoretical proposals to counter the increasing needs have either been to create a source through genetic engineering of porcine donors for xenotransplantation (with more potent immunosuppression protocols) or recreate one's organ in a pig using interspecies blastocyst complementation for exogenic organ transplantation (without immunosuppression). Another promising avenue has been organ banking through cryopreservation for transplantation. Although ice free preservation and acceptable early function following rewarming is critical for success in transplantation, the immunological response that predominantly defines short- and long-term graft survival has failed to captivate attention to date. It is well sorted that thermal and metabolic stress incurred at 4 °C during recovery and reperfusion of organs for clinical transplantation has varying impact on graft survival. Considering the magnitude of cellular imbalance and injury at sub-zero/ultralow temperatures in addition to the chemical toxicity of cryoprotective agents (CPA), it is essential to assess and address the immunological response associated following transplantation to maximize the success of cryopreservation.
Background Chronic pancreatitis is a debilitating disease resulting from many causes. The subset with hereditary/genetic pancreatitis (HGP) not only has chronic pain, but also an increased risk for ...pancreatic cancer. Long-term outcomes of total pancreatectomy (TP) and islet autogeneic transplantation (IAT) for chronic pancreatitis due to HGP are not clear. Study Design We reviewed a prospectively maintained database of 484 TP-IATs from 1977 to 2012 at a single center. The outcomes (eg, pain relief, narcotic use, β-cell function, health-related quality of life measures) of patients who received TP-IAT for HGP (protease trypsin 1, n = 38; serine protease inhibitor Kazal type 1, n = 9; cystic fibrosis transmembrane conductance regulator, n = 14; and familial, n = 19) were evaluated and compared with those with non−hereditary/nongenetic causes. Results All 80 patients with HGP were narcotic dependent and failed endoscopic management or direct pancreatic surgery. Post TP-IAT, 90% of the patients were pancreatitis pain free with sustained pain relief; >65% had partial or full β-cell function. Compared with nonhereditary causes, HGP patients were younger (22 years old vs 38 years old; p ≤ 0.001), had pancreatitis pain of longer duration (11.6 ± 1.1 years vs 9.0 ± 0.4 years; p = 0.016), had a higher pancreas fibrosis score (7 ± 0.2 vs 4.8 ± 0.1; p ≤ 0.001), and trended toward lower islet yield (3,435 ± 361 islet cell equivalent vs 3,850 ± 128 islet cell equivalent; p = 0.28). Using multivariate logistic regression, patients with non-HGP causes (p = 0.019); lower severity of pancreas fibrosis (p < 0.001); shorter duration of years with pancreatitis (p = 0.008); and higher transplant islet cell equivalent per kilogram body weight (p ≤ 0.001) were more likely to achieve insulin independence (p < 0.001). There was a significant improvement in health-related quality of life from baseline by RAND 36-Item Short Form Health Survey and in physical and mental component health-related quality of life scores (p < 0.001). None of the patients in the entire cohort had cancer of pancreatic origin in the liver or elsewhere develop during 2,936 person-years of follow-up. Conclusions Total pancreatectomy and IAT in patients with chronic pancreatitis due to HGP cause provide long-term pain relief (90%) and preservation of β-cell function. Patients with chronic painful pancreatitis due to HGP with a high lifetime risk of pancreatic cancer should be considered earlier for TP-IAT before pancreatic inflammation results in a higher degree of pancreatic fibrosis and islet cell function loss.
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