Role of gastric peroral endoscopic myotomy (GPOEM) in chronic gastroparesis management after pancreas transplantation.

Gastroparesis is a common complaint among patients with diabetes. Symptoms tend to improve following successful pancreas transplantation (PTx), but persist despite euglycemia in a subset of patients. We aimed to assess the benefit of gastric peroral endoscopic myotomy (G-POEM) in persistent gastroparesis following PTx. This was a single center retrospective review of all patients who underwent G-POEM for persistent gastroparesis following PTx. Patient demographics, pre and post procedure perception of symptom severity according to the patient assessment of upper gastrointestinal symptoms severity index (PAGI-SYM), gastroparesis cardinal symptom index (GCSI) score, and 36-item short form survey (SF36) score along with gastric emptying scintigraphy (GES) were analyzed. Seven PTx recipients underwent G-POEM for persistent gastroparesis symptoms. The majority were female. All reported nausea/vomiting, abdominal pain, bloating, and post prandial fullness prior to G-POEM. The post procedure survey scores improved in all patients although this was not significant. The improvement in gastric emptying on GES was statistically significant. G-POEM is a relatively new treatment option for gastroparesis. While it requires specialized proceduralist and training, we have documented improvement in the management of symptoms. With increasing experience, we anticipate more significant benefit in post PTx patients with persistent symptoms of gastroparesis undergoing G-POEM.

Simultaneous pancreas and kidney transplant after bilateral lung transplant for a recipient with cystic fibrosis.

Cystic fibrosis (CF) is an inherited autosomal recessive disorder. Despite optimized therapy, the majority of affected individuals ultimately die of respiratory failure. Lung transplantation is the only available therapy that deals definitively with the end-stage pulmonary disease and has become the treatment of choice for some of these patients. As patients with CF are living longer, extrapulmonary manifestations may develop including pancreatic failure, which manifests as exocrine insufficiency and CF-related diabetes (CFRD). Both of these can be managed through pancreas transplantation. We have previously reported our series of three simultaneous lung and pancreas transplants in patients with CF, which were complicated by surgical issues for both the thoracic and abdominal portions, rejection and resistant infections with disappointing long-term survival. Based on these results, a sequential approach was adopted: first, the thoracic transplant; and second, once the patient has recovered, the abdominal transplants. This is the first reported case of pancreas and kidney transplantation performed after a lung transplant in a patient with CF. It demonstrates a successful approach to treating CF with a lung transplant, and in an effort to improve the patient's long-term outcome, treating CFRD and pancreatic enzyme insufficiency, with a subsequent pancreas transplant.

Distal allograft pancreatectomy for graft salvage after pancreas transplantation.

Early pancreas allograft failure most commonly results from vascular thrombosis. Immediate surgical intervention may permit pancreas allograft salvage, typically requiring thrombectomy. In cases of partial allograft necrosis secondary to splenic arterial thrombosis, distal allograft pancreatectomy may allow salvage of at least half of the pancreas allograft with retention of function. We retrospectively reviewed four cases of simultaneous pancreas and kidney recipients who required distal allograft pancreatectomy for splenic artery thrombosis with necrosis of the distal pancreas. Three of the four maintained long-term allograft function with euglycemia independent of insulin at six months to six years of follow-up, and all patients continue to maintain normal renal allograft function. Early diagnosis and early intervention are essential in order to salvage the pancreas allograft in the case of thrombosis. Distal allograft pancreatectomy can be performed safely and result in excellent long-term outcomes in select patients.

Pancreas transplantation for cystic fibrosis: A frequently missed opportunity.

Cystic fibrosis (CF) is an inherited autosomal recessive disorder. Despite optimized therapy, the majority of affected individuals ultimately die of respiratory failure. As patients with CF are living longer, extra-pulmonary manifestations may develop including pancreatic failure, which manifests as exocrine insufficiency, and CF-related diabetes (CFRD). Both of these can be managed through pancreas transplantation. Pancreas transplantation is usually performed in combination with another organ, most often with a kidney transplant for end-stage diabetic nephropathy. In the CF patient population, the two settings where inclusion of a pancreas transplant should be considered would be in combination with a lung transplant for CF pulmonary disease, or in combination with a liver for CF-related liver disease with cirrhosis. This report will discuss this topic in detail, including a review of the literature regarding combinations of lung/pancreas and liver/pancreas transplant.

Pancreas transplantation would be easy if the recipients were not diabetic: A practical guide to post-operative management of diabetic complications in pancreas transplant recipients.

Diabetes mellitus remains a major public health problem throughout the United States with over $300 billion spent in total cost of care annually. In addition to being a leading cost of kidney failure, diabetes causes a host of secondary hyperglycemic-related complications including gastroparesis and orthostatic hypotension. While pancreas transplantation has been established as an effective treatment for diabetes, providing long-term normoglycemia in recipients, the secondary complications of diabetes mellitus persist complicating the post-operative course of an otherwise successful pancreas transplantation. This review describes the mechanism and impact of diabetic gastroparesis and orthostatic hypotension in the post-operative course of pancreas transplant patients and analyzes the various treatment modalities, based on current data and extensive experience at our institution, to treat these respective complications. While gastroparesis and orthostatic hypotension remain challenging post-operative conditions, the establishment of institutional protocols and step-up treatment algorithms can help define more effective therapies.

Effect of volatile anesthetics on early and delayed outcomes in pancreas transplantation.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a common cause of allograft dysfunction and patient morbidity in solid organ transplantation. This study compares the effect of different inhaled anesthetics on early IRI and clinical outcomes in pancreas allograft recipients. METHODS: Data were extracted retrospectively for pancreas transplants at a single center over a 15-year period. Early postoperative pancreatic amylase and lipase levels were used as a marker for graft injury. Clinical outcomes measured included length of hospital stay, readmission, and graft survival. RESULTS: There were 625 pancreas transplants included in the analysis with 3 primary inhaled anesthetics: sevoflurane (53%), desflurane (35%), and isoflurane (12%). In the first 30 days post-transplant, peak amylase was lowest for sevoflurane (147) followed by desflurane (159) and isoflurane (229) (p = .03). Peak lipase levels followed the same trend (peak values 118, 131, and 135, respectively; p = .02). Early graft loss, length of hospital stay, and readmission within 3 months were similar among all three anesthetic groups. There was no difference in 10-year graft survival by Cox regression. CONCLUSIONS: Sevoflurane and desflurane are associated with lower peak amylase and lipase levels postoperatively in pancreas transplantation. Short- and long-term clinical outcomes were equivalent for the three agents.

Contrast Administration to the Deceased Kidney Donor Has No Impact on Post-Transplant Outcomes.

BACKGROUND: Contrast-induced acute kidney injury may occur in patients undergoing imaging studies. This study reviews all deceased kidney donors at a single center during a 15-y period to determine if donor contrast exposure results in contrast-induced acute kidney injury in the donor or is associated with worse outcomes in the transplant recipient. METHODS: Donor and recipient renal functions were recorded, including donor serum creatinine and recipient delayed graft function, creatinine clearance at 1 y, and early and late graft survival. Donor contrast exposure was recorded as the number of preprocurement contrasted studies. RESULTS: Donor and recipient records were available for 1394 transplants (88%). There were 51% of donors who received any contrasted study (38%, one study; 12%, two studies, and 1%, three studies). Donor contrast exposure was not associated with significant differences in preprocurement serum creatinine levels. Post-transplant, donor contrast exposure was associated with risk of neither delayed graft function (4% for all) nor early kidney graft loss. Creatinine clearance at 1 y was equivalent. Five-year Cox regression demonstrated higher graft survival for contrast-exposed grafts (P = 0.03). CONCLUSIONS: There is no negative effect of donor contrast administration on early and late kidney graft function. These findings included donor kidneys exposed to as many as three contrasted studies.

Transversus abdominis plane (TAP) block for laparoscopic live donor nephrectomy: Continuous catheter infusion provides no additional analgesic benefit over single-injection ropivacaine.

BACKGROUND: Transversus abdominis plane (TAP) blocks are useful for adjunctive pain control following laparoscopic live donor nephrectomy (LLDN). The objective was to determine if TAP catheter provides additional analgesia compared with single-injection TAP block alone for kidney donors. METHODS: In this prospective, double-blinded, randomized controlled trial, LLDN patients received a single TAP injection of 30 mL 0.2% ropivacaine and had a catheter inserted into the TAP space. Postoperatively, either 0.2% ropivacaine (TAP catheter group; TAP-C) or saline (TAP saline group; TAP-S) was infused at 10 mL/h. Pain scores, narcotic usage, nausea, and sedation were evaluated at 1, 12, 24, 36, 48, and 60 hours. RESULTS: The study population included 70 patients (35 randomly assigned to each group). No differences in pain scores, narcotic usage, nausea, or sedation were observed at any time point (with the exception of lower median pain score for TAP-S at 60 hours; 3.2 vs 3.9 for TAP-C; P = .03). CONCLUSIONS: The lower pain score for placebo group at 60-hour postoperative is likely clinically insignificant. The TAP catheter infusion provided no benefit over a single-injection TAP block; thus, the added risk and cost are not supported. Liposomal bupivacaine should be evaluated in future studies.

Pancreas transplantation following total pancreatectomy for chronic pancreatitis.

BACKGROUND: Total pancreatectomy for chronic pancreatitis leads to brittle diabetes and challenging glycemic control with half of all patients experiencing severe hypoglycemia, many requiring medical intervention or hospitalization. Pancreas transplantation has the potential to manage both the endocrine and the exocrine insufficiency in this patient population. METHODS: Between June 1, 2005, and July 1, 2016, 8 patients with brittle diabetes following total pancreatectomy underwent pancreas transplantation. All grafts had systemic venous and enteric exocrine drainage. Data included demographics, graft and patient survival, pre- and post-transplant supplementation with pancreatic enzymes, and narcotic usage. RESULTS: Patient survival rate at 1 and 3 years was 88%. Pancreas graft survival rate of those alive at 1 year was 100% and 86%, respectively. About 75% of these patients remained insulin-free until their time of death, loss of follow-up, or present day. Of the patients with maintained graft function at 3 years, none required further hospitalization for glycemic control. About 75% of these patients have also maintained exocrine function without pancreatic enzyme supplementation. CONCLUSIONS: Pancreas transplant can treat both exocrine and endocrine insufficiency and give long-term insulin-free survival and should be considered as a viable treatment option for patients who have undergone total pancreatectomy for chronic pancreatitis.

Comparison of methods of providing analgesia after pancreas transplant: IV opioid analgesia versus transversus abdominis plane block with liposomal bupivacaine or continuous catheter infusion.

BACKGROUND: Current practices emphasize a multimodal approach to perioperative analgesia due to higher efficacy and decreased opioid usage. Analgesia for pancreas transplant (PT) has traditionally been managed with intravenous (IV) opioids, and reports of transversus abdominis plane (TAP) blocks are limited in this population. METHODS: Three interventions were compared in adult PT patients, including IV opioids, TAP catheter, and TAP block with liposomal bupivacaine. Time to return of intestinal function and oral diet, postoperative pain scores, opioid usage, and length of stay were recorded. RESULTS: Study included 197 PT patients: 62 (32%) standard care, 90 (45%) TAP catheters with continuous 0.2% ropivacaine, and 45 (23%) single liposomal bupivacaine TAP block. Pain scores were lowest for the IV opioid group (P < 0.001). The liposomal bupivacaine group had lower pain scores on postoperative days (POD) 1-5 than the TAP catheter group. Opioid use during POD 1-5 was lower for both TAP block groups (P = 0.03). Time to bowel function was faster for the TAP block groups (P < 0.05). CONCLUSIONS: Compared with IV opioid analgesia, TAP block interventions were associated with lower overall use of opioids and a faster time to intestinal function following pancreas transplant.

Steroid-free three-drug maintenance regimen for pancreas transplant alone: Comparison of induction with rabbit antithymocyte globulin +/- rituximab.

Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two-drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three-drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose). As of October 2007, a single dose of rituximab (150 mg/m2 ) was added. Maintenance consisted of tacrolimus, sirolimus and mycophenolate mofetil. From 2004 to 2017, 166 PTA were performed. Graft loss at 7 and 90 days were 4% and 5%, and 1-year patient and graft survival were 97% and 91%. Comparing induction without and with rituximab, there was no significant difference in 7- or 90-day graft loss, 1-year patient or graft survival, or in the rate of rejection or infection. Rabbit antithymocyte globulin induction and steroid withdrawal followed by a three-drug immunosuppression regimen is an excellent strategy for PTA recipients.

Excellent outcomes in combined liver-kidney transplantation: Impact of kidney donor profile index and delayed kidney transplantation.

The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver-kidney transplantation (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on kidney donor profile index [KDPI]) or the delayed approach KT contributes to improved patient survival. In total, 130 CLKTs were performed between 2002 and 2015, 69 with simultaneous KT (group S) and 61 with delayed KT (group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50 ± 15 hours). All patients were categorized according to the KDPI score: 1%-33%, 34%-66%, and 67%-99%. Recipient and donor characteristics were comparable within groups S and D. Transplant outcomes were comparable within groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. The combination of delayed KT and KDPI 1%-33% resulted in 100% patient survival at 3 years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3 years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more extended criteria donor and donation after circulatory death kidneys. Liver Transplantation 24 222-232 2018 AASLD.

Pancreas transplantation using compatible but non-identical ABO blood group donors.

BACKGROUND: There are limited data on the outcomes of pancreas transplants using ABO non-identical but compatible (NIC) donors. METHODS: A review of all pancreas transplants from a single institution from 01/2003 to 07/2016 (n = 606) revealed 41 recipients of a NIC donor pancreas which were matched for age, race, gender, year, and type of transplant with 41 ABO identical cases. Groups were compared for allograft survival, incidence of acute cellular rejection (ACR), length of hospital stay, 3-month readmissions and transfusion requirements. Serum haptoglobin and lactate dehydrogenase were used to identify hemolysis in patients requiring repeated transfusions without overt blood loss. RESULTS: The 1-year graft survival was 100% and 88% in the study and control groups. In the study group, 6/41(14%) developed hemolysis, all of which were ABO O into A. All responded to donor blood type specific transfusions. DISCUSSION: There are limited data on outcomes of solid organ transplant using NIC donors with almost none specifically addressing pancreas transplantation. In this study, graft survival was similar but 14% developed hemolysis, which was transient and treated with transfusion of donor blood type specific blood. CONCLUSION: Non-identical but compatible pancreas transplants have similar graft survival compared to ABO identical. Hemolysis may occur so some caution is required.

Pain interventions for organ transplant patients undergoing incisional hernia repair: Is epidural or transversus abdominus plane block a better option?

BACKGROUND: Postoperative pain management in transplant recipients undergoing incisional herniorraphy is challenging. Historically limited to intravenous or oral opioids, alternatives including transversus abdominus plane (TAP) block catheters and thoracic epidural catheters have been introduced. The aim of this study was to determine whether TAP catheters and thoracic epidural analgesia significantly impacted on postoperative pain and opioid usage in transplant recipients undergoing incisional hernia repair. METHODS: This single-center retrospective study included 154 patients undergoing incisional hernia repair from January 2011 to June 2015. Of these, 56 received epidurals, 51 received TAP catheters, and 47 received no intervention. RESULTS: Demographic profiles were comparable among the three groups including type of previous transplant and type of hernia surgery. Thoracic epidural analgesia was associated with lower median, mean, and maximum pain scores (P < 0.001) and less opioid requirement (P < 0.001). There was no difference in pain scores and opioid usage among the TAP catheter and no intervention groups. There was no difference in time to first flatus or first bowel movement, length of hospital stay, individual opioid-related side effects, and adverse reactions among the three groups. CONCLUSION: This study supports the use of thoracic epidural analgesia in patients undergoing hernia repair after transplant surgery.

A Novel Approach in Combined Liver and Kidney Transplantation With Long-term Outcomes.

OBJECTIVE: The aim of this study was to compare the outcomes of simultaneous and delayed implantation of kidney grafts in combined liver-kidney transplantation (CLKT). BACKGROUND DATA: Delayed function of the renal graft (DGF), which can result from hypotension and pressor use related to the liver transplantation (LT), may cause worse outcomes in CLKT. METHODS: A total of 130 CLKTs were performed at Indiana University between 2002 and 2015 and studied in an observational cohort study. All kidneys underwent continuous hypothermic pulsatile machine perfusion until transplant: 69 with simultaneous kidney transplantation (KT) (at time of LT, group 1) and 61 with delayed KT (performed at a later time as a second operation, group 2). All patients received continuous veno-venous hemodialysis during the LT. Propensity score match analysis in a 1:1 case-match was performed. RESULTS: Mean kidney cold ischemia time was 10 ± 3 and 50 ± 15 hours, for groups 1 and 2 (P < 0.0001), respectively. The rate of DGF was 7.3% in group 1, but no DGF was seen in group 2 (P = 0.0600). Kidney function was significantly better in group 2, if the implantation of kidneys was delayed >48 hours (P < 0.01). Patient survival was greater in group 2 at 1 year (91%), and 5 year (87%) post-transplantation (P = 0.0019). On multivariate analysis, DGF [hazard ratio (HR), 165.7; 95% confidence interval (CI), 9.4-2926], extended criteria donor kidneys (HR, 15.9; 95% CI 1.8-145.2), and recipient hepatitis C (HR, 5.5; 95% CI 1.7-17.8) were significant independent risk factors for patient survival. CONCLUSIONS: Delayed KT in CLKT (especially if delayed >48 h) is associated with improved kidney function with no DGF post-KT, and improved patient and graft survival.

Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria.

BACKGROUND: Enteric hyperoxaluria (EH) occurs with a rate of 5-24% in patients with inflammatory bowel disease, ileal resection and modern bariatric surgery. The excessive absorption of calcium oxalate causes chronic kidney disease (CKD) in patients with EH. In the literature, a single experience was reported in combined intestine-kidney transplantation (CIKTx) in patients with CKD due to EH. METHODS: After a report of 2 successful cases of CIKTx in patients with EH and CKD, one was performed at our center in a 59-year-old Caucasian female who developed intestinal failure with total parenteral nutrition (TPN) dependence after a complication post-bariatric surgery. Before CIKTx, she underwent kidney transplantation alone (KTA) twice, which failed due to oxalate nephropathy. RESULTS: In July 2014, the patient underwent CIKTx and bilateral allograft nephrectomy to avoid EH and oxalate stone burden. The postoperative course was complicated with acute tubular necrosis due to the use of high pressors related to perioperative bleeding. The patient was discharged 79 days after CIKTx with a serum creatinine (sCr) of 1.2 mg/dl and free of TPN. Her sCr increased at 7 months and a renal biopsy showed oxalate nephropathy. SLC26A6 (oxalate transporter) staining was significantly diminished in native duodenum/rectum as well as in intestinal allograft compared to control. CONCLUSIONS: KTA in patients with CKD secondary to EH should not be recommended due to high risk of recurrence. Although other centers showed good long-term outcomes in CIKTx, our patient experienced recurrence of EH due to oxalate transporter defect, early kidney allograft dysfunction and prolonged antibiotic use.

Late pancreas retransplantation.

Pancreas retransplantation, excluding immediate retransplantation for graft thrombosis, is a technically treacherous operation with the added challenges of adhesions from the prior transplant and difficulties identifying usable recipient vessels. The goal of this study was to review our single-center experience with late pancreas retransplantation. Charts for all pancreas transplant recipients between 01/2003 and 04/2013 were reviewed for demographics, graft and patient survival, length of stay (LOS), readmissions, and technical complications. Of 473 pancreas transplants, there were 20 late pancreas retransplants compared to 441 first transplants. There were no significant differences in donor or recipient demographics. There was no significant difference in graft or patient survival. The mean and median lengths of stay were 22 and nine d, respectively (range 5-175 d), and 11 recipients required readmission within the first three months post-transplant. Five patients were reexplored in the early postoperative period for an enteric leak at the site of the primary allograft (n = 1), complications of percutaneous gastrostomy tube placement (n = 1), hemorrhage (n = 1), and negative laparotomy for hyperglycemia (n = 2). Pancreas retransplantation is technically challenging but can be safely performed with graft and recipient survival comparable to primary transplants.

Value of magnetic resonance imaging in evaluating the pancreatic allograft transplant complications.

PURPOSE: To retrospectively investigate the value of magnetic resonance imaging (MRI) in detecting complications following pancreas transplant. MATERIALS AND METHODS: Institutional review board approved this retrospective HIPAA-compliant study and waived informed patient consent. We identified all allograft pancreas transplant patients at our institution from 2001 to January 2014 who had all pertinent post-transplant imaging and clinical data available. Transplant type was documented. Patients were divided into two groups according to post-transplant period (group A; <12 months, group B; ≥12 months). We evaluated the parenchymal enhancement using contrast-enhanced MRI of the allograft and determined the mean percentage of parenchymal enhancement (MPPE) overall and in various abnormalities, the vessel patency, any peripancreatic fluid collection, and the ductal anatomy. We correlated these with clinical results using t test, χ (2), and Fisher's exact test; p < 0.05 was considered significant. RESULTS: 51 patients (34 male, mean age 43.7 years) were identified, 28 (55%) of whom had abnormal imaging findings; transplant rejection-related necrosis (n = 7), fluid collections (n = 7), vascular stenosis (n = 4), isolated venous thromboses (n = 3), acute pancreatitis (n = 3), pancreatic and peripancreatic abscesses (n = 2), pseudoaneurysm (n = 1), and small-bowel obstruction (n = 1). Pre vs. post-contrast pancreatic MPPE at 1 min was 120% in the normal allografts and 115% in the allografts with pancreatitis and without necrosis (p > 0.05). MPPE at 1 min was only 9% in the allografts rejections with necrosis/infarction. More complications were found in group A than group B (p < 0.05). CONCLUSIONS: Contrast-enhanced MRI is useful for the non-invasive assessment of pancreas transplant complications.

Pancreas after kidney transplantation: why is the most logical option the least popular?

PURPOSE OF REVIEW: Despite recent improvements in outcomes for pancreas transplantation in general, including graft survival following pancreas after kidney (PAK) transplantation, there has been a consistent decline in the number of PAK transplants performed in the USA. The purpose of the present review is to analyze the advantages and disadvantages of PAK transplantation compared with simultaneous pancreas and kidney (SPK) transplantation and to review recent publications in an attempt to explain this phenomenon. RECENT FINDINGS: PAK transplantation has historically been associated with inferior pancreas allograft survival compared with SPK transplantation. Under modern immunosuppression protocols, pancreas allograft survival has improved substantially with rare immunological graft loss. According to several recent publications, it is controversial whether there is a survival advantage related to performing the pancreas transplant once the recipient has had a living donor renal transplant (LDRTx). SUMMARY: Considering that patient survival following SPK transplantation is significantly superior to that of recipients of LDRTx with type 1 diabetes alone and that LDRTx has demonstrated clear superiority in terms of renal allograft and patient survival over cadaveric renal transplantation, it would seem that PAK transplantation should be revisited as the option of choice for uremic recipients with diabetes.