De novo head and neck cancer after liver transplant with antibody-based immunosuppression induction

Background Powerful antibody-based immunosuppression induction is now used routinely during organ transplantation, and may place patients at even higher risk of post-transplant cancer. Materials and Methods Incidence of de-novo head and neck cancer was extracted from the records of 1685 consecutive adult, deceased donor liver transplant recipients with a minimum 1-year follow-up from 2001 to 2015. There were 121 patients positively identified as having developed de-novo head and neck cancer post-liver transplant. Records of these patients were analyzed to determine demographics, history of cancer pre-liver transplant, de-novo cancer type and location, treatment modalities, and alcohol and tobacco exposure. Results Of the 121 patients who developed cancer of the head and neck (7%), there were 103 cutaneous (6%) and 25 non-cutaneous (1%). For non-cutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (p<0.001), any smoking history (p=0.05), and increasing exposure to tobacco (p<0.01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop non-cutaneous cancer (p=0.06), but a survival advantage for patients who develop cutaneous cancer (p<0.01). Conclusions The incidence and pattern of head and neck cancer in this population of liver transplant patients was similar to those published previously, suggesting that induction immunosuppression does not increase risk of these types of cancers. Long term survival was worse for patients with non-cutaneous cancers, but better for those with cutaneous cancers, though the reason is unclear

Computed tomography measures of nutrition in patients with end-stage liver disease provide a novel approach to characterize deficits

Aim Patients with cirrhosis and end-stage liver disease (ESLD) develop severe nutrition deficits that impact on morbidity and mortality. Laboratory measures of nutrition fail to fully assess clinical deficits in muscle mass and fat stores. This study employs computed tomography imaging to assess muscle mass and subcutaneous and visceral fat stores in patients with ESLD. Methods This 1:1 case-control study design compares ESLD patients with healthy controls. Study patients were selected from a database of ESLD patients using a stratified method to assure a representative sample based on age, body mass index (BMI), gender, and model for end-stage liver disease score (MELD). Control patients were trauma patients with a low injury severity score (<10) who had a CT scan during evaluation. Cases and controls were matched for age +/- 5 years, gender, and BMI +/- 2. Results There were 90 subjects and 90 controls. ESLD patients had lower albumin levels (p<0.001), but similar total protein levels (p=0.72). ESLD patients had a deficit in muscle mass (-19%, p<0.001) and visceral fat (-13%, p<0.001), but similar subcutaneous fat (-1%, p=0.35). ESLD patients at highest risk for sarcopenia included those over age 60, BMI< 25.0, and female gender. We found degree of sarcopenia to be independent of MELD score. Conclusions These results support previous research demonstrating substantial nutrition deficits in ESLD patients that are not adequately measured by laboratory testing. Patients with ESLD have significant deficits of muscle and visceral fat stores, but a similar amount of subcutaneous fat

Pancreas transplantation using compatible but non‐identical ABO blood group 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 NIC pancreas transplants have similar graft survival compared to ABO identical. Hemolysis may occur so some caution is required

Impact of Donor Pre-Procurement Cardiac Arrest (PPCA) on Clinical Outcomes in Liver Transplantation

BACKGROUND Transplantation of liver grafts from deceased donors who experienced cardiac arrest prior to liver procurement is now common. This single-center study analyzed the impact of pre-donation arrest time on clinical outcomes in liver transplantation. MATERIAL AND METHODS Records of all orthotopic liver transplants performed at a single center over a 15-year period were reviewed. Donor records were reviewed and total arrest time was calculated as cumulative minutes. Post-transplant liver graft function was assessed using laboratory values. Graft survival was assessed with Cox regression analysis. RESULTS Records for 1830 deceased donor transplants were reviewed, and 521 donors experienced pre-procurement cardiac arrest (28%). Median arrest time was 21 min (mean 25 min, range 1-120 min). After transplant, the peak alanine aminotransferase and bilirubin levels for liver grafts from donors with arrest were lower compared to those for donors without arrest (p40 min arrest) demonstrated no statistically significant difference in survival at 10 years. Subgroup analysis of 93 donation after cardiac death grafts showed no significant difference for these same outcomes. CONCLUSIONS These results support the use of select deceased liver donors who experience pre-donation cardiac arrest. Pre-donation arrest may be associated with less early allograft dysfunction, but had no impact on long-term clinical outcomes. The results for donation after cardiac death donors were similar

Multivisceral Transplant is a Viable Treatment Option for Patients with Nonresectable Intra-abdominal Fibromatosis

Background Intra-abdominal fibromatosis often involves the mesentery root which is non-resectable by conventional surgery. Multivisceral transplant (MVT), as a potential cure to non-resectable fibromatosis, has rarely been reported and the prognosis is unknown. Methods Six patients who underwent MVT for intra-abdominal fibromatosis were reviewed. Clinicopathological features, immunohistochemistry for β-catenin, p53, and Ki67, and outcomes were evaluated. Appropriate data for comparative analysis were obtained from a cohort of 24 patients who underwent conventional resection for intra-abdominal fibromatosis. Results Among six MVT patients, four had familial adenomatous polyposis (FAP). Two patients had an initial intestinal transplantation, three had multiple prior surgeries, and two had adjuvant therapy. One patient died of hemorrhagic stroke shortly after MVT, and five patients (83%) survived with a median follow-up of 64 months. The 1-year and 5-year survival rates were 67% for all five patients. Two patients had recurrences after MVT and one of them had FAP. In comparison, six of 24 patients who underwent conventional surgery had FAP; six (25%) had recurrences and three had FAP. For FAP patients; the mean recurrence time was 13 months for MVT versus 6 months for conventional surgery. Ki67 proliferative index, β-catenin, and p53 expression did not significantly correlate to recurrence. Conclusions Multivisceral transplant (MVT) is a viable option for patients who have non-resectable intra-abdominal fibromatosis with promising surviving rates, although recurrence still occurs. Surgical margin, Ki67 proliferative index, β-catenin, and p53 expression are not predicative for recurrence of fibromatosis

One Year Incidence of Infection in Pediatric Intestine Transplantation

Background: This study reports the infection rate, location of infection, and pathogen causing bacterial, fungal, or viral infections in intestine transplant recipients at a pediatric transplant center. Methods: Records from a pediatric center were reviewed for patients receiving an intestine transplant. Positive cultures and pathology reports were used to diagnose bacterial, fungal, and viral infections and also to determine location and infectious agent. Risk for infection was assessed based on liver or colon inclusion, and immunosuppression induction, as part of the intestine transplant. Results: During the study period 52 intestine transplants were performed on 46 patients. Bacterial, fungal, and viral infection rates were 90%, 25%, and 75%, respectively. Enterococcus (non-vancomycin resistant enterococci (VRE)) species were the most common pathogens and were isolated from 52% of patients. VRE was present in 12% of transplant recipients. Candida species were the most common fungal pathogens (23% of patients). Respiratory viral infections were common (44%) and cytomegalovirus infection rate was 17%. Common sites of infection were bloodstream, urinary, and upper respiratory tract. Colon and liver inclusion in the transplant graft was not associated with increased risk of infection, nor was addition of rituximab to the immunosuppression induction protocol. Conclusion: Post-intestine transplant infections are ubiquitious in the pediatric population, including high rates of infection from bacterial, viral and fungal sources. Inclusion of the liver and/or colon as a component of the transplant graft did not appear to greatly impact the infectious risk. Adding rituximab to the immunosuppression induction protocol did not impact on infectious risk

Combination therapy for severe portopulmonary hypertension in a child allows for liver transplantation

Severe PPHTN is a contraindication to liver transplantation and predicts an abysmal 5‐year outcome. It is defined as a resting mPAP >45 mm Hg with a mean pulmonary artery wedge pressure of 3 wood units in the setting of portal hypertension. There have been limited reports of successful treatment of PPHTN leading to successful liver transplantation in adults, and one reported use of monotherapy as a bridge to successful liver transplant in pediatrics. To our knowledge, we describe the first use of combination therapy as a successful bridge to liver transplantation in a pediatric patient with severe PPHTN. This report adds to the paucity of data in pediatrics on the use of pulmonary vasodilator therapy in patients with severe PPHTN as a bridge to successful liver transplantation. Early diagnosis in order to mitigate or avoid the development of irreversible pulmonary vasculopathy that would preclude candidacy for liver transplantation is crucial, but our report demonstrates that combination therapy can be administered safely, quickly, and may allow for successful liver transplantation in patients with severe PPHTN

Post‐intestine transplant graft‐versus‐host disease: Associated with inclusion of a liver graft and with a high mortality risk

Introduction This study reports the incidence, anatomic location, and outcomes of graft‐versus‐host disease (GVHD) at a single active intestine transplant center. Methods Records were reviewed for all patients receiving an intestine transplant from 2003 to 2015. Pathology reports and pharmacy records were reviewed to establish the diagnosis, location, and therapeutic interventions for GVHD. Results A total of 236 intestine transplants were performed during the study period, with 37 patients (16%) developing GVHD. The median time to onset of disease was 83 days, with 89% of affected patients diagnosed in the first year post‐transplant. Mortality for affected patients was 54% in the one‐year after GVHD diagnosis. Skin lesions were the most common manifestation of GVHD. Other sites of disease included lungs, bone marrow, oral mucosa, large intestine, and brain. The incidence of GVHD was 16% in adult patients, and slightly lower in pediatric recipients (13%). In adults, increasing graft volume (isolated versus multi‐organ) and liver inclusion were associated with increasing risk of GVHD, though this was not seen in pediatric patients. Conclusion Overall, 16% of intestine transplant recipients developed GVHD. GVHD is associated with high mortality, and disease in the lungs, brain, and bone marrow was universally fatal

Donation After Circulatory Arrest in Pancreas Transplantation: A Report of 10 Cases

Introduction Transplantation of pancreas allografts procured from donation after circulatory death (DCD) remains uncommon. This study reviews a series of pancreas transplants at a single center to assess the donor and recipient characteristics for DCD pancreas transplant and to compare clinical outcomes. Methods DCD procurement was performed with a 5-minute wait time from pronouncement of death to first incision. In 2 patients, tissue plasminogen activator was infused as a thrombolytic during the donor flush. All kidney grafts were placed on pulsatile perfusion. Results There were 606 deceased donor pancreas transplants, 596 standard donors and 10 DCD donors. Of the 10 DCD transplants, 6 were simultaneous pancreas-kidney and 4 were pancreas transplant alone. The average time from incision to aortic cannulation was less than 3 minutes. The median total ischemia time for the DCD grafts was 5.4 hours, compared with 8.0 hours for standard donors (P = .15). Median length of hospital stay was 7 days for both groups, and there were no episode of acute cellular rejection in the first year post-transplant for the DCD group (4.2 % for standard group, P = .65). There was no difference in early or late graft survival, with 100% graft survival in the DCD group up to 1 year post-transplant. Ten-year Kaplan-Meier analysis shows similar graft survival for the 2 groups (P = .92). Conclusions These results support the routine use of carefully selected DCD pancreas donors. There were no differences in graft function, postoperative complications, and early and late graft survival

Excellent outcomes in combined liver-kidney transplantation: Impact of KDPI and delayed kidney transplantation

The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver-KT (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on KDPI) or the delayed approach KT contributes to improved patient survival. 130 CLKT were performed between 2002-2015; 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±15h). 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. 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 ECD and DCD kidneys