Improved Quality of Life Among Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation-Single Center Experience With Large Cohort of Patients.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3 years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.

Spleen-preserving total pancreatectomy and islet autotransplantation with complete preservation of the splenic arterial and venous supply does not impact islet yield and function.

BACKGROUND: Standard total pancreatectomy and islet autotransplantation (TPIAT) for chronic pancreatitis includes splenectomy, but TPIAT can be performed without splenectomy by full preservation of the blood supply to the spleen. METHODS: We compared the metabolic and clinical outcomes of patients who underwent TPIAT at our center between 2015 and 2021 with or without splenectomy. A total of 89 patients were included in the study, and 17 of them underwent spleen-preserving total pancreatectomy (SPTP). RESULTS: The two study groups had similar demographic and metabolic parameters. Short-term morbidity and long-term outcomes were similar. The operative time was significantly shorter with splenectomy: a median of 9.91 h (interquartile range [IQR] 8.89-10.83) compared to 10.78 h (IQR 10.2-11.6) for SPTP (P = 0.021). There was no difference between the groups in postoperative morbidity. Metabolic outcomes at 1 year were better in the SPTP group compared to the splenectomy group, with a median daily insulin requirement of 7 units (IQR 4-12) vs 15 units (IQR 7-26; P = 0.049) and a median C-peptide at 1 year of 0.65 (IQR 0.40-1.26) vs 1.00 (IQR 0.80-1.90; P = 0.63). The reduction in morphine milligram equivalents per day over time was significantly better in the SPTP group (P < 0.001), as was the decrease in pain score (P < 0.001). CONCLUSION: TPIAT with full arterial and venous preservation of the spleen had no adverse impact on islet yield or function. TPIAT can be safely and effectively performed with preservation of the spleen and the entire splenic artery and vein. The spleen should be preserved when feasible in every TPIAT surgery.

Longitudinal profiling of plasma and urine metabolites during liver regeneration in living liver donors.

BACKGROUND: Knowledge of metabolic processes affected by major hepatectomy (MHx), and the metabolic pathways involved in liver regeneration and recovery of function, is limited and mainly derived from animal models. Assessment of restoration of hepatic function is essential in human living liver donors (LD). METHODS: We used a targeted metabolomic approach to longitudinally quantify changes in plasma and urine biomarkers from healthy LD. The biomarkers were analyzed before MHx and at scheduled intervals up to 12 months thereafter. RESULTS: Marked changes were found in the concentration of 15 primary and secondary plasma bile acids. Most significant changes occurred 2 days after MHx and persisted for up to 3 months. In addition, there were significant changes in acylcarnitine, phospholipid, and amino acid metabolism. The sum of aromatic amino acids and the Fischer ratio, both metabolic markers of liver damage, and the symmetrically demethylated arginine to arginine ratio, a marker of kidney function, were affected. CONCLUSIONS: This is the first comprehensive longitudinal study investigating metabolic processes during recovery of liver function after MHx in LD. It provides further evidence of full restoration of metabolic processes 3 months after MHx and supports future investigation to understand how metabolic changes affect donors' hepatic function.

Utilization of a SARS-CoV-2-positive donor for liver transplantation.

Liver transplantation rates have been negatively affected by the pandemic caused by coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current practice in the liver transplant community is to avoid utilizing SARS-CoV-2-positive donors for liver transplantation unless there is a compelling reason such as recipient illness severity. In this case, we report the use of a donor who had a positive exposure to and symptom history for COVID-19 and tested positive for SARS-CoV-2 on admission for a liver transplant recipient with primary sclerosing cholangitis and a Model of End-Stage Liver Disease score of 23 with no known COVID-19 exposures. We focus on the decision to accept this particular organ, as well as the discussion with the recipient about the unknowns of disease transmission and risk associated with this donor. The current case argues that transplant programs should begin to consider low-risk donors with positive SARS-CoV-2 testing for recipients who have the potential to benefit from liver transplantation, which may not only be those with the most severe illness.

Cost Analysis of Liver Acquisition Fees Before and After Acuity Circle Policy Implementation.

Importance: Acuity circles (AC) liver allocation policy was implemented to eliminate donor service area geographic boundaries from liver allocation and to decrease variability in median Model of End-stage Liver Disease (MELD) score at transplant and wait list mortality. However, the broader sharing of organs was also associated with more flights for organ procurements and higher costs associated with the increase in flights. Objective: To determine whether the costs associated with liver acquisition changed after the implementation of AC allocation. Design, Setting, and Participants: This single-center cost comparison study analyzed fees associated with organ acquisition before and after AC allocation implementation. The cost data were collected from a single transplant institute with 2 liver transplant centers, located 30 miles apart, in different donation service areas. Cost, recipient, and transportation data for all cases that included fees associated with liver acquisition from July 1, 2019, to October 31, 2020, were collected. Exposures: Primary liver offer acceptance with associated organ procurement organization or charter flight fees. Main Outcomes and Measures: Specific fees (organ acquisition, surgeon, import, and charter flight fees) and total fees per donor were collected for all accepted liver donors with at least 1 associated fee during the study period. Results: Of 213 included donors, 171 were used for transplant; 90 of 171 (52.6%) were male, and the median (interquartile range) age of donors was 41.0 (30.0-52.8) years in the pre-AC period and 36.9 (24.0-48.8) years in the post-AC period. There was no significant difference in the post-AC compared with pre-AC period in median (range) MELD score (24 [8-40] vs 25 [6-40]; P = .27) or median (range) match run sequence (15 [1-3951] vs 10 [1-1138]; P = .31), nor in mean (SD) distance traveled (155.83 [157.00] vs 140.54 [144.33] nautical miles; P = .32) or percentage of donors requiring flights (58.5% [69 of 118] vs 56.8% [54 of 95]; P = .82). However, costs increased significantly in the post-AC period: total cost increased 16% per accepted donor (mean [SD] of $52 966 [13 278] vs $45 725 [9300]; P < .001) and 55% per declined donor (mean [SD] of $15 865 [3942] vs $10 217 [4853]; P < .001). Contributing factors included more than 2-fold increases in the proportions of donors incurring import fees (31.4% [37 of 118] vs 12.6% [12 of 95]; P = .002) and surgeon fees (19.5% [23 of 118] vs 9.5% [9 of 95]; P = .05), increased acquisition fees (10% increase; mean [SD] of $43 860 [3266] vs $39 980 [2236]; P < .001), and increased flight expenses (43% increase; mean [SD] of $12 904 [6066] vs $9049 [5140]; P = .002). Conclusions and Relevance: The unintended consequences of implementing broader sharing without addressing organ acquisition fees to account for increased importation between organ procurement organizations must be remedied to contain costs and ensure viability of transplant programs.

Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients.

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c ), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.

Selective screening imaging of the aortoiliac arterial system in kidney transplant candidates with non-contrast pelvic computed tomography.

Non-contrast pelvic computed tomography (CT) can detect severe iliac artery calcifications that present technical contraindications to kidney transplantation (TCT). We screened 454 asymptomatic patients with a history of any of the following: hemodialysis >10 years, diabetes mellitus >20 years, coronary artery disease (CAD) with percutaneous or surgical interventions, carotid disease, diabetes with below-/above-knee amputations, and heart-kidney transplantation candidacy. Patients with normal dorsalis pedis and/or tibialis posterior pulses were not screened. A total of 8.4% had severe calcifications with TCT; CT determined laterality for implantation in 13.9%. No patients with the following characteristics were classified as TCT: age <40 years, hemodialysis >10 years, carotid arterial disease, prior lower extremity amputation, or heart-kidney transplantation candidacy. CAD was associated with TCT in univariate though not multivariate analysis. Limiting screening to patients >40 years, with DM >20 years, or with CAD, 9.8% had a TCT and CT determined transplant laterality in 14.2%. Screening for severe iliac artery calcifications is useful for selected kidney transplantation candidates over age 40. It can assist with laterality choice or surgeon determination of TCT. Cost and radiation exposure risks should be weighed against the morbidity risks from unnecessary surgery.

Dallas UtErus Transplant Study: Early Outcomes and Complications of Robot-assisted Hysterectomy for Living Uterus Donors.

BACKGROUND: Uterus transplantation is a treatment for absolute uterine infertility and can be performed with living and deceased donors. Given the safety and increased utilization of robotic assistance with other gynecologic and transplant donor operations, we adopted a robot-assisted approach to donor hysterectomy. This study compared early outcomes and morbidity of the robot-assisted approach to donor hysterectomy with the traditionally performed open approach and addressed whether the robot-assisted approach is safe and offers advantages for the donor. METHODS: Our institution has performed 18 living donor hysterectomies for uterus transplantation. This retrospective review compared the last 5 cases utilizing a robot-assisted technique and vaginal extraction of the uterus graft with the first 13 cases performed with an open laparotomy technique. Demographic, intraoperative, and postoperative data were examined. RESULTS: There were no differences between the robot-assisted and the open living donor group with respect to age, body mass index, or gynecological history. Although the median operative time was shorter for the open approach (6.27 versus 10.46 h), the donors' median estimated blood loss, length of hospital stay, and length of sick leave were less with the robot-assisted approach. There was no conversion to open hysterectomy in the robot-assisted cases, and the incidence of complications was similar between the 2 groups. There was no difference in early graft function. CONCLUSIONS: These preliminary results show that robot-assisted living donor hysterectomy is feasible and safe for the donors; it allows a faster postoperative recovery and the same early graft function.

Outcomes of Islet Autotransplantation in Chronic Pancreatitis Patients with Complete Acinar Atrophy.

Total pancreatectomy with islet autotransplantation (TPIAT) is a promising treatment for refractory chronic pancreatitis (CP). Pathological features of CP include progressive fibrosis in pancreas parenchyma, atrophy, and/or ductal occlusion. Complete acinar atrophy (CAA) caused by chronic fibrosis and necroinflammation results in exocrine sufficiency and may influence islet isolation characteristics during TPIAT. In this analysis of patients who underwent TPIAT at our center, we compared transplant outcomes among those with CAA (n = 5) vs non-acinar atrophy (NAA; matching controls, n = 36). Data were analyzed using one-way analysis of variance with Bonferroni post hoc test or Student's t test. Pancreas digestion was longer in CAA than in NAA cases (18.6 vs 14.6 min) despite a lower pancreas weight (55.2 vs 91.2 g). Obtained tissue volume was 1.0 ml in the CAA group and 12.1 ml in the NAA group. Both groups had similar islet viability (96%) and islet dose (CAA, 3,391 IEQ/kg; NAA, 4141.1 IEQ/kg). During islet infusion, serum cytokine (IL-6, IL-8, and MCP-1) levels and plasma hsa-miR-375 levels were lower in the CAA group than in the NAA group, but not significantly. Serum tumor necrosis factor α levels at 3 h after infusion were significantly higher in CAA group than in NAA group. After TPIAT, the metabolic outcomes of the CAA group were comparable with that of the NAA group. Narcotics usage decreased significantly over 24 months in both groups, with the CAA group reporting being pain free at 12 months. Complete atrophy of acinar cells of pancreas did not significantly impact islet yield or endocrine function after TPIAT.

Types of Leadership and How to Use Them in Surgical Areas.

Surgery is a very complex, changing, and, sometimes, threatening environment. Emotional intelligence is a key skill for surgical leaders. Authoritarian, hierarchical, transactional, transformational, adaptive, situational, and servant-shepherd leadership can all be used in surgical leadership. Patient care must be the priority for surgical leaders.

The Evolution of Transplantation From Saving Lives to Fertility Treatment: DUETS (Dallas UtErus Transplant Study).

OBJECTIVE: We report the results of the first 20 uterus transplants performed in our institution. SUMMARY BACKGROUND DATA: Uterus transplantation (UTx) aims at giving women affected by absolute uterine-factor infertility the possibility of carrying their own pregnancy. UTx has evolved from experimental to an established surgical procedure. METHODS: The Dallas Uterus Transplant Study (DUETS) program started in 2016. The uterus was transplanted in orthotopic position with vascular anastomoses to the external iliac vessels and removed when 1 or 2 live births were achieved. Immunosuppression lasted only for the duration of the uterus graft. RESULTS: Twenty women, median age 29.7 years, enrolled in the study, with 10 in phase 1 and 10 in phase 2. All but 2 recipients had a congenital absence of the uterus. Eighteen recipients received uteri from living donors and 2 from deceased donors. In phase 1, 50% of recipients had a technically successful uterus transplant, compared to 90% in phase 2. Four recipients with a technical success in phase 1 have delivered 1 or 2 babies, and the fifth recipient with a technical success is >30 weeks pregnant. In phase 2, 2 recipients have delivered healthy babies and 5 are pregnant. CONCLUSIONS: UTx is a unique type of transplant; whose only true success is a healthy child birth. Based on results presented here, involving refinement of the surgical technique and donor selection process, UTx is now an established solution for absolute uterine-factor infertility.

Anti-inflammatory Approach With Early Double Cytokine Blockade (IL-1ß and TNF-α) Is Safe and Facilitates Engraftment in Islet Allotransplantation.

BACKGROUND: The approach to reducing nonspecific inflammation after islet allotransplantation has been designed to improve engraftment, typically using 1 agent. We report results with the use of combination inflammatory blockade consisting of anti-interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. METHODS: Nine patients underwent islet allotransplantation under a prospective research protocol using double cytokine blockade with anti-TNF-α (etanercept, d 0, 3, 7, 10) and IL-1ß (anakinra, d 0-7) at the time of each islet infusion. The primary endpoint, assessed 2 years after the last islet transplant, was the elimination of severe hypoglycemic events and hypoglycemia unawareness, with proper glycemic control, and detectable serum C-peptide. RESULTS: No thrombotic events or infectious complications were associated with combined IL-1ß and TNF-α blockade. Six patients became insulin independent, 2 had partial function, and 1 had primary nonfunction. After 24-month follow-up, 6 of 9 patients had excellent glycemic control, hemoglobin A1c ≤6.5%, and no episodes of hypoglycemia unawareness. Eight patients developed HLA alloantibodies at various time points (class 1, 5; class 2, 6), with enhanced T-cell alloreactivity. One patient retained good graft function despite having anti-glutamic acid decarboxylase 65 antibodies. CONCLUSIONS: The use of double cytokine blockade is safe, with reduction of inflammation at transplantation and presumably with better engraftment. However, it does not influence later islet loss from T-cell-mediated autoimmunity and alloimmunity, which require other strategies to maintain long-term islet function.

Impact of microbial contamination of the islet product during total pancreatectomy with islet autotransplantation.

BACKGROUND: The combined use of interleukin-1ß and tumor necrosis factor-α blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection. METHODS: We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1ß and TNF-blockade treatment at our center. RESULTS: Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < .0001) and insulin independence rate (P = .036) at 6 months were significantly lower for patients receiving contaminated product. CONCLUSIONS: These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes.

Effect of subcutaneous tissue depth on outcomes of kidney transplantation.

Although post-kidney transplant (KT) wound complications are associated with elevated body mass index (BMI), BMI is not an accurate surrogate of obesity. On the other hand, subcutaneous depth (SQD) measurement is a direct marker of truncal obesity. We examined outcomes of differing intraoperative SQD measurements in 113 KT-only recipients over 20 months. Recipients' median age was 51 years; median BMI, 28 kg/m2; and mean SQD, 2.9 cm. Patients were stratified into groups of SQD ≤2.5 cm, >2.5-5 cm, and >5 cm. An SQD of >2.5 to 5 cm correlated with a BMI of 30 kg/m2 (obesity) and an SQD >5 cm correlated with a BMI >35 kg/m2 (severe obesity). Degree of SQD was not associated with more frequent technical complications such as fascial dehiscence, lymphocele formation, renal artery thrombosis/stenosis, urine leak, or ureteral stenosis. However, an SQD >2.5 cm was a risk factor for requiring a wound vacuum-assisted closure device. There was no difference in graft or patient survival among the three SQD groups. Obesity, as measured directly by SQD, was not associated with increased technical complications or poor outcomes after KT. As expected, there was a higher incidence of wound complications in the higher SQD groups requiring intervention.

The impact of surgical complications on the outcome of total pancreatectomy with islet autotransplantation.

Total pancreatectomy with islet autotransplantation is a promising treatment for refractory chronic pancreatitis. We analyzed postoperative complications in 83 TPIAT patients and their impact on islet graft function. We examined patient demographics, preoperative risk factors, intraoperative variables, and 30- and 90-day postoperative morbidity and mortality. Daily insulin requirement, HbA1c, C-peptide levels, and narcotic requirements were analyzed before and after surgery. Adverse events were recorded, with postoperative complications graded according to the Clavien-Dindo classification. There was no mortality in this patient group. Postoperative complications occurred in 38 patients (45.7%). Patients with postoperative complications were readmitted significantly more often within 30 days (p = 0.01) and 90 days posttransplant (p < 0.0003) and had a significantly longer hospital stay (p = 0.004) and intensive care unit stay (p = 0.001). Insulin dependence and graft function assessed by HbA1c, C-Peptide and insulin requirements did not differ significantly by these complications. Postoperative complications after TPIAT are associated with longer hospital and intensive care unit stay and with readmission; however, the surgical complications do not affect islet graft function.

Donor-specific Antibodies, Immunoglobulin-free Light Chains, and BAFF Levels in Relation to Risk of Late-onset PTLD in Liver Recipients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a neoplastic complication of transplantation, with early cases largely due to immunosuppression and primary Epstein-Barr virus infection. Etiology may differ for later-onset cases, but the contributions of immunosuppression, immune reactivity to the donor organ, and chronic B cell activation are uncertain. METHODS: We conducted a case-control study of late-onset PTLD (diagnosed >1 year posttransplant) in a cohort of liver recipients. We assessed serum samples (obtained >6 months before diagnosis in cases) from N = 60 cases and N = 166 matched controls for donor-specific antibodies (DSAs, evaluable for N = 221 subjects), immunoglobulin kappa and lambda free light chains (FLCs, N = 137), and B cell activating factor (BAFF, N = 226). Conditional or unconditional logistic regression was used to calculate adjusted odds ratios (aORs). RESULTS: Circulating DSAs were less common in PTLD cases than controls (18% vs 30%), although this difference was borderline significant (aOR, 0.51; 95% confidence interval [CI], 0.24-1.10; P = 0.09). Donor-specific antibodies against class II HLA antigens predominated and likewise showed a borderline inverse association with PTLD (aOR, 0.58; 95% CI, 0.27-1.24). The FLC levels were less frequently abnormal in cases than controls, but measurements were available for only a subset and confidence intervals were wide (elevated kappa: aOR, 0.57; 95% CI, 0.15-2.12; P = 0.40; elevated lambda: aOR, 0.68; 95% CI, 0.30-1.50; P = 0.34). B cell-activating factor levels were not associated with PTLD. CONCLUSIONS: Our results suggest that circulating DSAs are associated with decreased risk of late-onset PTLD. Because DSAs may develop in the setting of underimmunosuppression, the inverse association with DSAs supports a role for immunosuppression in the etiology of late-onset PTLD.

The role of multiorgan procurement for abdominal transplant in general surgery resident education.

BACKGROUND: To assess the impact of participation of multiorgan procurement (MP) by general surgery (GS) residents on surgical knowledge and skills, a prospective cohort study of GS residents during transplant surgery rotation was performed. METHODS: Before and after participation in MPs, assessment of knowledge was performed by written pre and post tests and surgical skills by modified Objective Structured Assessment of Technical Skill (OSATS) score. Thirty-nine residents performed 84 MPs. RESULTS: Significant improvement was noted in the written test scores (63.3% vs 76.7%; P < 0.001). Better surgical score was associated with female gender (15.4 vs 13.3, P = <0.01), prior MP experience (16.2 vs 13.7, P = 0.03), and senior level resident (15.1 vs 13.0, P = 0.03). Supraceliac aortic dissection (P = 0.0017) and instrument handling (P = 0.041) improved with more MP operations. CONCLUSIONS: Participation in MP improves residents' knowledge of abdominal anatomy and surgical technique.

The impact of allogenic blood transfusion on the outcomes of total pancreatectomy with islet autotransplantation.

BACKGROUND: Allogenic blood transfusion (ABT) may be needed for severe bleeding during total pancreatectomy with autotransplantation (TPIAT), but may induce inflammation. This study investigated the impact of ABT. METHODS: With a population of 83 patients who underwent TPIAT from 2006 to 2014, this study compared cytokine levels, patient characteristics, islet characteristics, metabolic outcomes, insulin requirements, and hemoglobin A1c for those who received a blood transfusion (BT) versus no blood transfusion (NBT). RESULTS: Initially, proinflammatory cytokines were moderately higher in the BT group than the NBT group. Despite longer procedures and more severe bleeding, the BT group had similar values to the NBT group for insulin requirements, serum C-peptide, hemoglobin A1c, and insulin independence rate. The probability of insulin independence was slightly higher in patients receiving ≥3 units of blood. CONCLUSION: ABT induced elevation of proinflammatory cytokines during the perioperative period in TPIAT, but these changes did not significantly change posttransplant islet function.