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 noncutaneous (1%). For noncutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (P < .001), any smoking history (P = .05), and increasing exposure to tobacco (P < .01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop noncutaneous cancer (P  = .06) but a survival advantage for patients who develop cutaneous cancer (P < .01). CONCLUSIONS: The incidence and pattern of head and neck cancer in this population of liver transplant recipients 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 noncutaneous 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.

BACKGROUND: Patients with cirrhosis and end-stage liver disease (ESLD) develop severe nutrition deficits that affect 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), sex, and model for end-stage liver disease score (MELD). Control patients were trauma patients with a low injury severity score (<10) who had a computed tomography scan during evaluation. Cases and controls were matched for age ± 5 years, sex, and BMI ± 2. RESULTS: There were 90 subjects and 90 controls. ESLD patients had lower albumin levels (P < .001), but similar total protein levels (P = .72). ESLD patients had a deficit in muscle mass (-19%, P < .001) and visceral fat (-13%, P < .001), but similar subcutaneous fat (-1%, P = .35). ESLD patients at highest risk for sarcopenia included those over age 60, BMI<25.0, and female sex. We found degree of sarcopenia to be independent of model for end-stage liver disease 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.

Impact of Volatile Anesthetic Agents on Early Clinical Outcomes in Liver Transplantation.

BACKGROUND: Few studies have assessed the ability of inhaled anesthetic agents to ameliorate ischemia-reperfusion injury (IRI) in liver transplantation (LT). This study compares inhaled anesthetics in early liver allograft IRI. LT recipient and organ donor data were extracted retrospectively for all LTs at a single center between 2001 and 2015. METHODS: LT recipient and organ donor data were extracted retrospectively for all LTs at a single center between 2001 and 2015. The choice of primary anesthetic agent was at the discretion of the anesthesiologist. Serum alanine aminotransferase (ALT) and total bilirubin (TB) levels were measured daily in the post-transplant period as measures of early graft injury and function. Survival and clinical outcomes are reported. RESULTS: There were 1291 primary LTs included in the analysis, with 3 primary inhaled agents: isoflurane (62%), desflurane (8%), and sevoflurane (30%). In the first 7 days post-transplant, the peak ALT level was lowest for desflurane (352), followed by sevoflurane (411) and isoflurane (481) (P = .09). All groups had similar ALT and TB by 7 days post-transplant. Graft survival for all 3 groups was statistically similar at 1, 7, and 30 days, with equivalent patient and graft survival at 1 year. CONCLUSIONS: All 3 agents had similar rates of early allograft dysfunction and renal dysfunction. Subgroup analysis of high-risk donor grafts showed no statistical difference. In conclusion, administration of desflurane or sevoflurane may provide some early hepatoprotection against IRI, but longer-term outcomes were equivalent for all agents.

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.

Allograft Pancreatectomy: Indications and Outcomes.

This study evaluated the indications, surgical techniques, and outcomes of allograft pancreatectomy based on a single center experience. Between 2003 and 2013, 47 patients developed pancreas allograft failure, excluding mortality with a functioning pancreas allograft. Early graft loss (within 14 days) occurred in 16, and late graft loss in 31. All patients with early graft loss eventually required allograft pancreatectomy. Nineteen of 31 patients (61%) with late graft loss underwent allograft pancreatectomy. The main indication for early allograft pancreatectomy included vascular thrombosis with or without severe pancreatitis, whereas one recipient required urgent allograft pancreatectomy for gastrointestinal hemorrhage secondary to an arterioenteric fistula. In cases of late allograft pancreatectomy, graft failure with clinical symptoms such as abdominal discomfort, pain, and nausea were the main indications (13/19 [68%]), simultaneous retransplantation without clinical symptoms in 3 (16%), and vascular catastrophes including pseudoaneurysm and enteric arterial fistula in 3 (16%). Postoperative morbidity included one case each of pulmonary embolism leading to mortality, formation of pseudoaneurysm requiring placement of covered stent, and postoperative bleeding requiring relaparotomy eventually leading to femoro-femoral bypass surgery 2 years after allograftectomy. Allograft pancreatectomy can be performed safely, does not preclude subsequent retransplantation, and may be lifesaving in certain instances.

Aminocaproic Acid (amicar) as an alternative to aprotinin (trasylol) in liver transplantation.

INTRODUCTION: This study compared clinical outcomes for a large number of liver transplant patients receiving intraoperative epsilon-aminocaproic acid (EACA), aprotinin, or no antifibrinolytic agent over an 8-year period. PATIENTS AND METHODS: Records for deceased donor liver transplants were reviewed. Data included antifibrinolytic agent, blood loss, early graft function, and postoperative complications. Study groups included low-dose aprotinin, high-dose aprotinin, EACA (25 mg/kg, 1-hour infusion), or no antifibrinolytic agent. RESULTS: Data were included for 1170 consecutive transplants. Groups included low-dose aprotinin (n = 324 [28%]), high-dose aprotinin (n = 308 [26%]), EACA (n = 216 [18%]), or no antifibrinolytic (n = 322 [28%]). EACA had the lowest intraoperative blood loss and required the fewest transfusions of plasma. Patients receiving no agent required the most blood transfusions. Early graft loss was lowest in the EACA group, and 90-day and 1-year patient survival rates were significantly higher for the low-dose aprotinin and EACA groups according to Cox regression. Complications were similar, but there were more episodes of deep vein thrombosis in patients receiving EACA. CONCLUSIONS: These results suggest that transitioning from aprotinin to EACA did not result in worse outcomes. In addition to decreased intraoperative blood loss, a trend toward improved graft and patient survival was seen in patients receiving EACA.

Closure of the abdominal wall with acellular dermal allograft in intestinal transplantation.

Loss of abdominal domain is a common problem in intestinal transplantation. Several surgical options are available perioperatively for abdominal wall reconstruction. This study reports the management and complications for intestinal transplant patients with abdominal wall closure either primarily or with foreign material. This single center study reviews the records of intestinal transplant patients between 2004 and 2010. Study outcomes included reoperation for dehiscence, hernia or enterocutaneous fistula. There were 37 of 146 patients (25%) who required implantation of foreign material at transplant. Of these 37, 30 (81%) had implantation of acellular dermal allograft (ADA) and 7 (19%) implantation of another mesh. Perioperative dehiscence was rare with 2/109 (2%) for primary closure, 0/30 (0%) for ADA and 1/7 (14%) for other mesh. There were 12/146 (8%) patients who underwent ventral hernia repair: primary closure 7/109 (6%), ADA 3/30 (10%) and other mesh 2/7 (28%). There were 4/146 (3%) patients who required surgery for enterocutaneous fistulas: 2/109 (2%) primary closure, 1/30 (3%) ADA and 1/7 (14%) synthetic mesh. Abdominal wall reconstruction with ADA biologic mesh provides an expeditious means of performing a tension-free closure of the fascial layer after intestinal transplantation with complications similar to those seen for primary closure.

Risk factors for native kidney dysfunction in patients with abdominal multivisceral/small bowel transplantation.

Kidney dysfunction is a recognized complication after non-renal solid organ transplantation, particularly after intestinal transplant. In our study, we reviewed data on 33 multivisceral transplant (MVT)- and 15 isolated small bowel (ISB)-transplant patients to determine risk factors for kidney dysfunction. Kidney function was estimated by modified diet in renal disease (MDRD) and Schwartz formula for adults and children, respectively. Acute kidney injury (AKI) was defined as an increase in the serum Cr (sCr) greater than twofold. Kidney function declined significantly at one yr after transplantation with 46% of subjects showing an estimated GFR (eGFR) <60 mL/min. Patients with an episode of AKI were more likely to have reduced eGFR than those without AKI (p < 0.025). In linear regression analyses, age, pre-transplant sCr, eGFR at postoperative day (POD) 30, 90, 180, 270, and tacrolimus level at POD 7 showed significant correlation with one yr post-transplant eGFR (p < 0.05). Pediatric patients and patients with MVT had lesser decline in kidney function compared with adults or patients with ISB. In conclusion, risk factors for post-transplant kidney dysfunction in intestinal transplantation included age, pre-transplant sCr, AKI episode, eGFR at POD 30, 90, 180, 270, and tacrolimus level at POD 7.

Histidine-tryptophan-ketoglutarate for pancreas allograft preservation: the Indiana University experience.

Histidine-tryptophan-ketoglutarate solution (HTK) has been scrutinized for use in pancreas transplantation. A recent case series and a United Network for Organ Sharing data base review have suggested an increased incidence of allograft pancreatitis and graft loss with HTK compared to the University of Wisconsin solution (UW). Conversely, a recent randomized, controlled study failed to show any significant difference between HTK and UW for pancreas allograft preservation. This study was a retrospective review of all pancreas transplants performed at Indiana University between 2003 and 2009 comparing preservation with HTK or UW. Data included recipient and donor demographics, 7-day, 90-day and 1-year graft survival, peak 30-day serum amylase and lipase, HbA1c and C-peptide levels. Of the 308 pancreas transplants, 84% used HTK and 16% UW. There were more SPK compared to pancreas after kidney and pancreas transplant alone in the HTK group. Donor and recipient demographics were similar. There was no significant difference in 7-day, 90-day or 1-year graft survival, 30-day peak serum amylase and lipase, HbA1c or C-peptide. No clinically significant difference between HTK and UW for pancreas allograft preservation was identified. Specifically, in the context of low-to-moderate flush volume and short cold ischemia time (

Immediate retransplantation for pancreas allograft thrombosis.

Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1-16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin-induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76-1137 days (mean 572 days). One-year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first-time pancreas transplantation.

Predictors of blood product use in orthotopic liver transplantation using the piggyback hepatectomy technique.

UNLABELLED: Orthotopic liver transplantation (OLT) has historically been associated with massive blood loss and hemodynamic instability related to the coexistence of varices, coagulopathy, thrombocytopenia, and portal hypertension. Piggyback hepatectomy (PGB) is a technique increasingly utilized in OLT to avoid veno-venous bypass and vena cava clamping. This study evaluated the factors associated with blood loss and blood product requirement in PGB. METHODS: This study is a retrospective review of the anesthesia preoperative and operative notes and computerized lab values for all adult cadaveric liver transplants over a 42-month period. These data were combined with the liver transplant database for analysis. Approximately 98% of the transplants were performed using a standard piggyback approach with no use of veno-venous bypass. RESULTS: Data were included for all 526 transplants performed during this time period. Estimated blood loss (EBL) was 1000 cc. Median transfusion requirement was 3 units packed red blood cells, 7 units fresh frozen plasma, and 6 units platelets. Multivariate linear regression demonstrated that predictors of EBL were age, MELD score, preoperative hemoglobin, initial fibrinogen, initial central venous pressure, and total anesthesia time. Predictors of PRBC useage were age, MELD score, preoperative hemoglobin, initial fibrinogen, and anesthesia time. Postoperatively increased transfusion requirement was associated with increased length of hospital stay and lower 90-day and 1-year graft and patient survivals. CONCLUSION: These results demonstrate that PGB can be safely accomplished in nearly all liver transplant patients without venovenous bypass or vena cava clamping and with less warm ischemia, which may ultimately be associated with less perioperative morbidity and improved outcomes.

Survival after disseminated invasive aspergillosis in a multivisceral transplant recipient.

Disseminated invasive aspergillosis is a serious and potentially lethal infectious complication of immunosuppressed individuals, including transplant recipients. We report here a successfully treated case of disseminated Aspergillus fumigatus infection involving the lungs, brain, and endocardium in a multivisceral transplant recipient. In addition to supportive measures, the patient was aggressively treated with a combination of three antifungal agents, and all immunosuppression was significantly lowered with close observation for rejection. After 3 months of therapy, the patient cleared the fungal infection, made a full recovery of his cerebral function, and was discharged to a rehabilitation facility.

Burn injuries in children with attention-deficit/hyperactivity disorder.

PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for traumatic injury than non-ADHD-children. Burn injuries in ADHD-children have not been studied. This study was conducted to determine differences in burn injuries between these groups. METHODS: The charts of all children ages 5-18, admitted over a 7-year period to a single regional pediatric burn center, were reviewed. ADHD-children were compared to non-ADHD-children regarding age and gender, type and extent of burn, and burn injury outcome. FINDINGS: There were 278 children included, 35 (13%) having ADHD. ADHD-children were more likely male but did not differ in age compared to non-ADHD-children. ADHD-children were more likely to experience a thermal rather than flame burn (83% versus 58% thermal, P < 0.01) and had more extensive burn injury (10% versus 5% median TBSA, P = 0.03). The ADHD group had a longer length of stay (11 versus 7 days, P = 0.05) and was less likely to be discharged to home (86% versus 93%, P = 0.17). CONCLUSIONS: ADHD-children do differ from non-ADHD-children in their pattern and extent of burn injury. The impulsivity and vigilance deficits that characterize ADHD may place these children at higher risk for specific types of burn injuries.

Current helmet and protective equipment usage among previously injured ATV and motorcycle riders.

Injury recidivism among trauma patients may be related to an individual pattern of high risk behaviors. The extent to which an injury episode modifies this behavior pattern is unknown. A self report, voluntary, anonymous, cross sectional survey was administered to motorcycle and all-terrain vehicle (ATV) riders at a popular recreation site. Data included demographics, injury history, and current usage of helmet and protective gear. Two hundred eighty surveys were completed. History of ATV/motorcycle related minor and major injury were reported by 21% and 9%, respectively. Persons with a history of minor ATV/motorcycle injury only were less likely to use a helmet or protective equipment (78% v 74%, p = 0.58 and 49% v 41%, p = 0.29). Persons with a history of any major ATV/motorcycle injury were also less likely to use a helmet or protective equipment (77% v 56%, p = 0.03 and 48% v 40%, p = 0.53). These findings suggest a pattern of persistent high risk behavior among previously injured persons.

Stented Lich-Gregoir ureteroneocystostomy: case series report and cost-effectiveness analysis.

UNLABELLED: Extravesical ureteroneocystostomy to reestablish urinary tract continuity in renal transplantation has been examined through a meta-analysis of more than 14,000 kidney transplants leading to the finding that stented anastomosis was associated with a lower urologic complication rate compared with nonstented anastomoses. Fourteen stents must be used to prevent one urologic complication. We now report the urologic complication rate in our case series in which a stented Lich-Gregoir anastomosis was routinely utilized. We present a cost-effectiveness analysis regarding the usage of ureteral stents. METHODS: The records of 395 consecutive renal transplants were reviewed. Minimum follow-up time was 6 months. The standard anastomosis was a Lich-Gregoir with a 6- or 8-F 12- or 14-cm J-J stent. Monitored urologic complications included postoperative vesicoureteral leak or ureteral necrosis, obstruction or stricture, or clinically significant hematuria. Charges in 2004 US dollars were reported by the hospital accounting office. RESULTS: Four urologic complications were noted-three leaks and one stricture (complication rate of 1.0%). There were no stent-related complications requiring reoperation. There were no cases in which the urologic complication led to graft loss or patient death. Total charges associated with stent use were $1,087 per patient, or $15,218 per urologic complication prevented. CONCLUSIONS: The urologic complication rate in this case series is similar to the five previously published randomized trials, as well as our previously published meta-analysis. These results support the routine use of a ureteral stent. Our analysis suggests that stent use is cost effective.

Statewide variation in the treatment of patients hospitalized with spleen injury.

HYPOTHESIS: Surgeons' treatment decisions for patients with spleen injuries in Washington State from January 1, 1990, through December 31, 1994, were different in rural compared with urban communities. DESIGN AND SETTINGS: Retrospective cohort analyses using the Death and Illness History Database for the state of Washington, which provides a cross-linked record of an individual's sequential hospitalizations. Counties were defined as metropolitan, urban, or rural on the basis of population density. PATIENTS: A total of 1905 patients (1927 hospitalizations) with an International Classification of Diseases, Ninth Revision, Clinical Modification, discharge diagnosis code of 865. MAIN OUTCOME MEASURES: Physician management decisions (perform a celiotomy or repair the spleen) were stratified by geographic region. RESULTS: Throughout the state, there was substantial variability in the treatment of spleen-injured patients. Factors associated with higher odds of splenectomy included older age, overall severity of injury, treatment in rural hospitals, and treatment in the earlier years of study. While the frequency of splenic salvage increased over time, hospital length of stay, rehospitalization, and 30-day mortality did not increase. CONCLUSIONS: Injury to the spleen is a common problem for which management decisions vary by geographic region, indicating that a single management protocol does not universally apply. To evaluate appropriateness of care by process measures, such as splenic injury management, will require that decision makers grant some latitude in management variability based on factors such as practice setting.

Medical students' attitudes toward physician-assisted suicide.

CONTEXT: In November 1994, Oregon became the first US state to legalize physician-assisted suicide (PAS) as an option for end-of-life care. OBJECTIVE: This study compares the attitudes and experiences of medical students in Oregon regarding PAS to those of fourth-year medical students in the United States outside Oregon. DESIGN: A survey of all students at the Oregon Health Sciences University and fourth-year medical students at 3 non-Oregonian US medical schools. PARTICIPANTS: Oregon medical students returned 227 questionnaires (58%), and 113 were returned from control schools (33%). RESULTS: A similar percentage of both study groups favored the legalization of PAS (64% vs 66%; P = .74). If the practice were legal, 55% of the total surveyed reported they "might be willing to write a lethal prescription," (50% Oregon students vs 60% control; P = .13 and 44% fourth-year Oregon students vs 60% control; P = .04). Among fourth-year students, 20% reported a request by a patient to the student or a preceptor for a lethal prescription in the past year (26% vs 16%; P = .09). CONCLUSIONS: This study demonstrates support for and willingness by many medical students to participate in PAS. Some medical students reported observation of PAS during their training experience. Fourth-year Oregon students reported significantly less willingness than other students to provide a patient with a lethal prescription, perhaps indicating hesitancy to include PAS in clinical practice.

Prevalence of harassment and discrimination among 1996 medical school graduates: a survey of eight US schools.

CONTEXT: Harassing and discriminating behaviors on the part of instructors or supervisors are known to affect the quality of work performed by medical students, influence their career decisions, and have other undetermined long-term consequences. OBJECTIVE: To assess the prevalence and forms of harassment and discrimination experienced by 1996 medical school graduates. DESIGN: A self-administered survey of harassment and discrimination mailed to graduating medical students. SETTING AND PARTICIPANTS: A total of 1001 graduating medical students at 8 US medical schools (4 public and 4 private), chosen from each of the 4 regions designated by the Association of American Medical Colleges for geographic categorization. OUTCOME MEASURE: The number of reported experiences of various forms of harassment and discrimination while attending medical school. RESULTS: Of 1001 surveys, 548 (55%) were returned. Overall, 46% of the students reported experiencing some form of harassment and 41% some form of discrimination from instructors or supervisors while attending medical school. Nonsexual verbal harassment was reported by 41%; sexual verbal harassment was reported by 10%. Discrimination based on gender was reported by 29% of students; discrimination based on race was reported by 12%. CONCLUSIONS: Harassment and discrimination of medical students by instructors and supervisors continue to occur frequently, and new approaches are needed to address these problems.