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.

Epidemiology and Risk Factors for Invasive Fungal Infections in Pancreas Transplant in the Absence of Postoperative Antifungal Prophylaxis.

Background: Invasive fungal infections (IFIs) remain a rare yet dreaded complication following pancreas transplantation. Current guidelines recommend antifungal prophylaxis in patients with 1 or more risk factors. At our center, single-dose antifungal prophylaxis is administered in the operating room but none subsequently, regardless of risk factors. Here we evaluate the 1-year incidence, outcome, and risk factors associated with IFI following pancreas transplantation. Methods: A retrospective, single-center cohort study was conducted in patients who underwent pancreas transplantation between 1 January 2009 and 31 December 2019. Records were manually reviewed, and cases were adjudicated using consensus definitions. The 1-year cumulative incidence, mortality, and risk factors were analyzed by Kaplan-Meier method and differences between populations were assessed with Fisher test and Mann-Whitney U test. Results: Three hundred sixty-nine recipients were included. Twelve IFIs were identified: candidiasis (8), aspergillosis (2), histoplasmosis (1), and cryptococcosis (1). Intra-abdominal infections were the most common presentation (5), followed by bloodstream infections (3), disseminated disease (2), pulmonary disease (1), and invasive fungal sinusitis (1). Median time to IFI was 64 days (interquartile range, 30-234 days). One-year cumulative incidence was 3.25% (95% confidence interval, 1.86%-5.65%). There were no significant differences between patients with or without IFI regarding type of transplant (P = .17), posttransplant dialysis (P = .3), rejection (P = .5), cytomegalovirus serostatus (P = .45), or reoperation (P = .19). For patients with IFI, the 1-year graft and patient survival rates were 58% versus 95% (P < .0001) and 75% versus 98.6% (P < .001), respectively. Conclusions: Our study suggests that the use of a single-dose antifungal prophylaxis administered in the operating room but none subsequently does not result in an increased incidence of IFI following pancreas transplantation.

Vasopressin for Post-kidney Transplant Hypotension.

Introduction: Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods: Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results: Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion: Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.

Procedure: Laparoscopic Donor Nephrectomy.

Minimally invasive approaches for laparoscopic donor nephrectomy are necessary to limit surgical morbidity, and technical challenges differ from those encountered during other laparoscopic renal surgeries. Presented here is a step-by-step guide for laparoscopic donor nephrectomy-focusing on pure laparoscopic and hand-assisted techniques. Both straight laparoscopic and hand-assisted nephrectomies were performed in healthy donors who met transplantation criteria in terms of global health and psychologic well-being. Patient positioning, trocar placement, surgical steps, incision closure, and postoperative care are reviewed. Standard equipment used to complete this procedure is itemized. This guide outlines indications, preoperative preparation, and procedural steps for laparoscopic donor nephrectomy. The techniques and the evolution thereof represent our experience since 2002 for 510 cases. The attached videos demonstrate a high-volume surgeon's typical approach while factoring in anatomical variation. In both cases, the donor nephrectomies were without incident and the patient's postoperative courses were without complication. A basic framework for donor nephrectomy is presented highlighting surgical steps we believe to be essential for graft preservation and ultimately effective transplantation. Although no two cases are the same, systematic approaches will allow for timely case completion, fewer complications, and better donor/recipient outcomes.

Combined liver-kidney transplantation with positive crossmatch: Role of delayed kidney transplantation.

BACKGROUND: Positive crossmatch (XM+) combined liver-kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver-kidney transplantations. METHODS: XM+ combined liver-kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. RESULTS: Of 183 combined liver-kidney transplantations performed (2002-2019), 114 (62%) were with "delayed" kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver-kidney transplantations, kidney transplant was "delayed" in 14 by an average of 47 hours (range 24-64 hours) from liver transplant. There was a significant reduction in both class I (mean pre-liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post-liver transplant and pre-delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre-liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre-liver transplant MFI 17,899 versus post-liver transplant and pre-delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver-kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM- combined liver-kidney transplantation. Whereas patient survival in recipients before "delayed" approach ("simultaneous"; n = 5) was 40% when liver-kidney transplants were performed simultaneously (P = .06). CONCLUSION: In sensitized combined liver-kidney transplantation recipients, the "delayed" kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

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.

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.

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.

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.

Living Donor Gifted Lithiasis: Long-Term Outcomes in Recipients.

OBJECTIVES: Presence of nephrolithiasis in a living donor has been at least a relative contraindication to living donor nephrectomy. The concern for stone recurrence and outcomes has been one of the reasons for reluctance to consider these medically complex donors. We evaluate long-term outcomes in recipients of kidney grafts from donors with nephrolithiasis, or history of nephrolithiasis, and provide results from our experience at Indiana University. MATERIALS AND METHODS: We retrospectively reviewed 57 donor-recipient pairs, where the allograft was received from a living donor with symptomatic calculi, or with imaging evidence of kidney stones, between 2003 and 2018. This research study was done in compliance with the ethical standards set forth in the Helsinki Congress. RESULTS: The mean age of recipients was 46±19 years and 58% were male. Kidney recipients were followed for a median of 3.5 years and 59.6% of patients had follow-up imaging studies. None of the recipients had obstructing renal calculi or related infections. None of the recipients required any interventions for recurrent calculi and no stone episode lead to adverse event to the graft. Hyperoxaluria and hypercalciuria were the most common risk factors in 24-hour urine collections obtained from donors. CONCLUSIONS: Our findings from a single large center looking at kidney recipient outcomes over a long follow-up period found that gifted lithiasis is a safe procedure. Careful selection of "medically complex donors" with kidney stones based on appropriate guidelines is a key step. Further studies are needed to help develop consensus guidelines.

Incisional Hernia After Orthotopic Liver Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: Incisional hernia (IH) is a well-known complication of orthotopic liver transplantation. Despite wide recognition of the impact of this problem, the incidence remains imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to November 2017 for abstracts documenting IH after orthotropic liver transplantation (OLT). The primary endpoint of this study was incidence of IH, secondary endpoints were time to hernia and recurrence. Three reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% CIs. RESULTS: After a review of 77 abstracts, 18 studies were graded as relevant. The methodological quality of studies was assessed with a minimum Oxford Centre for Evidence-Based Medicine level of 2B. These represent a cohort of 981 patients with IH after OLT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidence of 15.1% (CI 12.1%-18.2%). Aggregate recurrence rate reported in the literature is 12.4% (CI 4.3%-20.5%). Overall reported time to IH after OLT was 42.9 months. CONCLUSIONS: Although reported incidences of IH after OLT vary widely across studies, an overall incidence of 15.1% is reported. This is a relatively late complication after transplantation. Recurrence of hernia after initial repair is 12.4% within this patient population.

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.

Impact of Recipient Age in Combined Liver-Kidney Transplantation: Caution Is Needed for Patients ≥70 Years.

Elderly recipients (≥70 y) account for 2.6% of all liver transplants (LTs) in the United States and have similar outcomes as younger recipients. Although the rate of elderly recipients in combined liver-kidney transplant (CLKT) is similar, limited data are available on how elderly recipients perform after CLKT. METHODS: We have previously shown excellent outcomes in CLKT using delayed kidney transplant (Indiana) Approach (mean kidney cold ischemia time = 53 ± 14 h). Between 2007 and 2018, 98 CLKTs were performed using the Indiana Approach at Indiana University (IU) and the data were retrospectively analyzed. Recipients were subgrouped based on their age: 18-45 (n = 16), 46-59 (n = 34), 60-69 (n = 40), and ≥70 years (n = 8). RESULTS: Overall, more elderly patients received LT at IU (5.2%) when compared nationally (2.6%). The rate of elderly recipients in CLKT at IU was 8.2% (versus 2% Scientific Registry of Transplant Recipient). Recipient and donor characteristics were comparable between all age groups except recipient age and duration of dialysis. Patient survival at 1 and 3 years was similar among younger age groups, whereas patient survival was significantly lower in elderly recipients at 1 (60%) and 3 years (40%) (P = 0.0077). Control analyses (replicating Scientific Registry of Transplant Recipient's survival stratification: 18-45, 46-64, ≥65 y) showed similar patient survival in all age groups. CONCLUSIONS: Although LT can be safely performed in elderly recipients, extreme caution is needed in CLKT due to the magnitude of operation.

Radiologic Assessment of Muscle and Fat Stores in Long-Term Type I Diabetics Referred for Pancreas Transplant Compared to Healthy Controls.

Type 1 diabetes (DM1) is associated with loss of skeletal muscle and bone mass and may affect body fat stores. This study employs computed tomography (CT) scans to assess the body composition of DM1 patients referred for pancreas transplant compared to healthy controls. A 1:1 case-control design matched study patients with otherwise healthy patients from the trauma database. Matching criteria included age ± 5 years, gender, and body mass index (BMI) ± 2kg/m2. Nutrition variables included serum albumin and protein levels, BMI, and CT measures of muscle mass and fat stores. There were 22 subjects and 22 controls (median DM1 duration 24 years). DM1 patients had less muscle mass and less subcutaneous fat but no difference in visceral fat. Patients with the greatest muscle deficit were those with DM1 greater than 20 years and those younger than age 40. DM1 patients maintain similar BMI and protein levels compared to healthy controls but have marked deficits of muscle and subcutaneous fat. These results inform the nutritional management of DM1 patients and quantify the muscle and fat deficits present in these patients. At highest risk are young patients and those with duration of DM1 over 20 years.

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.

Correlation and Prediction of Living-Donor Remaining Function by Using Predonation Computed Tomography-Based Volumetric Measurements: Role of Remaining Kidney Volume.

OBJECTIVES: Kidney volume in healthy living donors may serve as a surrogate marker of renal function. Here, we evaluated whether preserved kidney volume correlated with and could predict donor renal function at 2 years postdonation using the CKD-EPI estimated glomerular filtration rate equation. MATERIALS AND METHODS: Healthy living donors (n = 208) with computed tomography volume measurements were evaluated for renal function before and after donation. Preserved kidney volume was adjusted to body surface area. Demographic characteristics (including race/ethnicity and sex) and renal function variables of donors were analyzed for postdonation renal function. RESULTS: Donor mean age was 39.4 ± 10.7 years (36.2% males, 91.9% white). Median adjusted preserved kidney volume was 180.6 mL. At 2 years postdonation, median estimated glomerular filtration rate was 62.4 mL/min (interquartile range, 54.8-73.2 mL/min). Predonation estimated glomerular filtration rate, age, and adjusted preserved kidney volume were found to be inde-pendent predictors of 2-year estimated glomerular filtration rate (P < .001). We further analyzed data by stratifying preserved kidney volumes into tertiles. Mean 2-year estimated glomerular filtration rates were 57.9 ± 12, 65 ± 16, and 73 ± 17 mL/min for lowest to highest tertile groups, respectively (P < .05). The odds ratio of having a 2-year postdonation estimated glomerular filtration rate of < 60 mL/min for donors in the lowest tertile group was 3.51 (95% confidence interval, 1.9-6.4; P < .001), whereas the risk for donors in the highest tertile group was 0.23 (95% confidence interval, 0.12-0.44; P< .001). Sensitivity analysis result was 0.764 (95% confidence interval, 0.69-0.82; P = .005) for adjusted preserved kidney volume and estimated glomerular filtration rate of < 60 mL/min. CONCLUSIONS: Remaining kidney volume before donation correlated with and predicted estimated glomerular filtration rate after donation. Remaining kidney volume should be assessed when selecting kidneys from healthy donors.