Microvascular activation and exocytosis after exposure to the serum from mismatched recipients by using donor microvascular cultures.

BACKGROUND: Microvascular injury resulting from activation and exocytosis are early signs of tissue damage caused by allografting. However, humoral anti-graft reactions are not easily detectable in transplant biopsies. The aim of this study was to establish a bioassay to recapitulate this process in a prospective approach. METHODS: The study was executed by using our previously established protocol to isolate and freeze the donors' microvascular endothelial cells (MVEC) at the transplantation (34 living-related donors and 26 cadaver donors); and to collect sera from the recipients before the transplantation, one-, three- and six-months after transplantation. The activation and exocytosis of the MVEC were determined by incubating the donors' cultures with the recipients' sera. We determined if there was any endothelial activation by quantifying the releases of monocyte chemotactic protein-1 (MCP-1) and interleukin 8 (IL-8) in supernatants and the expressions of membrane intercellular adhesion molecule-1 (CD54) and intercellular adhesion molecule-1 (CD106) by flow cytometry. Endothelial exocytosis was determined by quantifying soluble E-selectin (CD62E) and cytoplasmic von Willebrand Factor (vWF) in supernatants. Endothelial activation or exocytosis was considered positive when the fold change (≧1.5) of post-transplantation to pre-transplantation was reached. We also monitored serum PRA and cytokines using Luminex multiple-plex and cytometric bead-based assay respectively. RESULTS: We found 41.2% recipients (14 out of 34, ranging from 1.5 to 5.2 folds, p < 0.05) exhibited positive MVEC activation in the first month after transplantation as determined by IL-8 levels; 26.5% recipients (9 out of 34, ranging from 1.5 to 11.8 folds, p < 0.05) by MCP-1 levels. In the group of three months post-transplantation, 70.6% patients were positive (12 out of 17, ranging from 1.8 to 87.1 folds, p < 0.05) by IL-8 increased levels; 24% recipients (4 out of 17, ranging from 1.8 to 50.5 folds, p < 0.05) measured by MCP-1 levels. However, these changes disappeared six months after transplantation. Flow cytometric data showed that a time-dependent of CD54+ and CD106+ expressions existed over the course of six months. Most CD54+ and CD106+ cells were CD31- (platelet-endothelial cell adhesion molecule-1), though CD31+/CD106+ (37.5%, 3 out of 8) and CD31+/CD106+ (25%. 2 out of 8) were seen. When comparing donor MVEC activation to their recipient's proinflammatory cytokine levels or PRA status, we could not draw a conclusion regarding the connections between them. The sera collected from recipients at either one- or three-months after allografting did not significantly induce the release of either soluble CD62E or vWF (p > 0.05), indicating exocytosis was not significantly involved in the acute phase of allografting. CONCLUSIONS: This bioassay enables us to detect the activation and exocytosis of donor MVEC elicited by respective sera from mismatched kidney recipients.

Neoadjuvant Chemoradiation Therapy Is Associated with Adverse Outcomes in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Cancer.

The use of neoadjuvant chemoradiation therapy in patients with pancreatic adenocarcinoma is emerging as an acceptable therapy option. The effects of neoadjuvant therapy on 30 days' outcomes in patients with pancreatic cancer are not well defined in the literature. NSQIP (2009-2012) was used. Only patients with a diagnosis of pancreatic cancer and those who underwent a Whipple were included in the analysis. Patient who underwent neoadjuvant chemoradiation therapy were compared with those who did not receive therapy. Main outcome measures were as follows: complications, ≥2 units of blood transfusions, length of stay, readmission rates, return to the operating room, and 30-day mortality. A total of 1445 patients (395: neoadjuvant chemoradiation and 1050: no neoadjuvant therapy) were identified. The mean age was 67 ± 12 years, and 51 per cent of the patients were male. Neoadjuvant chemoradiation therapy was associated with increase in readmission rates (18% vs 12.2%, P 0.02), unanticipated return to the operating room (2.3% vs 1.1%, P 0.03) with no difference in mortality rates. Neoadjuvant chemoradiation therapy is associated with increase in inhospital complications. These differences in outcomes may be explained by the more advance stage of pancreatic cancer in these subsets of patients. Resource utilization and preoperative rehabilitation are of utmost significance to overcome this rise in complications associated with neoadjuvant chemoradiation therapy.

Transfer of peanut allergy from donor to recipient after liver transplant.

31 years old female with a history of contact dermatitis, eczema, allergic rhinitis, pernicious anemia, alopecia areata and latent tuberculosis was treated concurrently with methotrexate along with isoniazid and pyridoxine. Five months into the therapy she developed acute onset jaundice progressing into fulminant liver failure with altered mentation and worsening liver function tests. Extensive workup including serological and histopathological evaluation revealed drug-induced liver injury as the etiology of her liver failure and she underwent a successful orthotropic liver transplant. On post-transplant follow-up at four months, she was noted to have an allergic reaction consisting of a perioral rash and swelling (without anaphylaxis) after receiving a kiss from her significant other who had just eaten a peanut butter chocolate. She denied any history of allergic reaction to peanuts prior to the transplant. Percutaneous skin testing revealed immediate hypersensitivity to peanut, hazelnut, and pecan believed to be acquired newly post-transplant. Further investigation revealed that the organ donor had a documented history of systemic anaphylaxis from the peanut allergy and a positive peanut-specific IgE level. Also, another parallel solid organ recipient (lung transplant) from the same organ donor experienced a serious anaphylactic reaction after peanut exposure. This is a case of food (peanut) allergy transfer from the donor to the recipient after the liver transplant. This case highlights the importance of incorporating known donor allergies as a part of pre-transplant screening, given the potentially serious consequences from the transfer of allergies to a previously anergic recipient.

Cell cycle plasticity driven by MTOR signaling: integral resistance to CDK4/6 inhibition in patient-derived models of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC), like many KRAS-driven tumors, preferentially loses CDKN2A that encodes an endogenous CDK4/6 inhibitor to bypass the RB-mediated cell cycle suppression. Analysis of a panel of patient-derived cell lines and matched xenografts indicated that many pancreatic cancers have intrinsic resistance to CDK4/6 inhibition that is not due to any established mechanism or published biomarker. Rather, there is a KRAS-dependent rapid adaptive response that leads to the upregulation of cyclin proteins, which participate in functional complexes to mediate resistance. In vivo, the degree of response is associated with the suppression of a gene expression signature that is strongly prognostic in pancreatic cancer. Resistance is associated with an adaptive gene expression signature that is common to multiple kinase inhibitors, but is attenuated with MTOR inhibitors. Combination treatment with MTOR and CDK4/6 inhibitors had potent activity across a large number of patient-derived models of PDAC underscoring the potential clinical efficacy.

Association Between Noninvasive Fibrosis Markers and Postoperative Mortality After Hepatectomy for Hepatocellular Carcinoma.

Importance: The selection criteria for hepatectomy for hepatocellular carcinoma (HCC) is not well established. The role of noninvasive fibrosis markers in this setting is unknown in the US population. Objective: To evaluate whether aspartate aminotransferase-platelet ratio index (APRI) and fibrosis 4 (Fib4) values are associated with perioperative mortality and overall survival after hepatectomy for HCC. Design, Setting, and Participants: In a multicenter cohort study, Veterans Administration Corporate Data Warehouse was used to evaluate a retrospective cohort of 475 veterans who underwent hepatectomy for HCC between January 1, 2000, and December 31, 2012, in Veterans Administration hospitals. Data analysis occurred between September 30, 2016, and December 30, 2017. Logistic regression, survival analysis, and change in concordance index analysis were performed to evaluate the association between APRI and Fib4 values and mortality. Exposures: The cohort was stratified based on preoperative APRI and Fib4 values. Analysis was performed accounting for the validated and established predictors of outcome. Main Outcomes and Measures: Thirty-day mortality, 90-day mortality, and overall survival were the primary outcomes. An APRI value greater than 1.5 was considered high risk (cirrhosis), and an Fib4 value greater than 4.0 was considered high risk (advanced fibrosis). Portal hypertension (diagnosis of ascites or encephalopathy indicates presence of portal hypertension) and Child-Turcotte-Pugh (CTP) class (A indicates preserved liver function; B, mild to moderate liver dysfunction) served as 2 other measures of liver function. Results: A total of 475 patients with HCC underwent hepatectomy. The mean (SD) age was 65.6 (9.4) years; Model for End-Stage Liver Disease score, 8.9 (3.1); and body mass index, 28.1 (4.9) (calculated as weight in kilograms divided by height in meters squared). A total of 361 patients (76.0%) were men, 294 (61.9%) were white; 308 (64.8%) were hepatitis C positive, and 346 (72.8%) were categorized as CTP class A. The most common surgical procedure was partial lobectomy, with 321 (67.6%) procedures. The APRI value greater than 1.5 vs 1.5 or lower was associated with increased 30-day mortality (odds ratio [OR], 6.45; 95% CI, 2.80-14.80) and 90-day mortality (OR, 2.65; 95% CI, 1.35-5.22), as was Fib4 greater than 4.0 vs Fib4 4.0 or lower for 30-day mortality (OR, 5.41; 95% CI, 2.35-12.50) and 90-day mortality (OR, 2.74; 95% CI, 1.41-5.35). Survival analysis showed that overall survival was significantly different for APRI greater than 1.5 vs 1.5 or lower (mean survival time, 3.6 vs 5.4 years; log-rank P < .001) and Fib4 greater than 4.0 vs 4.0 or lower (mean survival time, 4.1 vs 5.3 years; log rank P = .01). Adjusted Cox proportional hazards regression analysis revealed that elevated APRI was significantly associated with worse survival (hazard ratio [HR], 1.13; 95% CI, 1.03-1.23) but Fib4 values were not (HR, 1.04; 95% CI, 0.99-1.09). Change in concordance index showed that APRI and Fib4 improved the ability of CTP class and portal hypertension to predict postoperative mortality. Conclusions and Relevance: Elevated APRI and Fib4 values, which are noninvasive markers of fibrosis, were associated with higher perioperative mortality. The APRI was also associated with worse overall survival. Use of APRI and Fib4 measures improved the ability of established markers to predict postoperative mortality. These findings suggest incorporating APRI and Fib4 to the selection process for hepatectomy for HCC as predictors associated with mortality may be warranted.

Transmission of Balamuthia mandrillaris by Organ Transplantation.

BACKGROUND: During 2009 and 2010, 2 clusters of organ transplant-transmitted Balamuthia mandrillaris, a free-living ameba, were detected by recognition of severe unexpected illness in multiple recipients from the same donor. METHODS: We investigated all recipients and the 2 donors through interview, medical record review, and testing of available specimens retrospectively. Surviving recipients were tested and treated prospectively. RESULTS: In the 2009 cluster of illness, 2 kidney recipients were infected and 1 died. The donor had Balamuthia encephalitis confirmed on autopsy. In the 2010 cluster, the liver and kidney-pancreas recipients developed Balamuthia encephalitis and died. The donor had a clinical syndrome consistent with Balamuthia infection and serologic evidence of infection. In both clusters, the 2 asymptomatic recipients were treated expectantly and survived; 1 asymptomatic recipient in each cluster had serologic evidence of exposure that decreased over time. Both donors had been presumptively diagnosed with other neurologic diseases prior to organ procurement. CONCLUSIONS: Balamuthia can be transmitted through organ transplantation with an observed incubation time of 17-24 days. Clinicians should be aware of Balamuthia as a cause of encephalitis with high rate of fatality, and should notify public health departments and evaluate transplant recipients from donors with signs of possible encephalitis to facilitate early diagnosis and targeted treatment. Organ procurement organizations and transplant centers should be aware of the potential for Balamuthia infection in donors with possible encephalitis and also assess donors carefully for signs of neurologic infection that may have been misdiagnosed as stroke or as noninfectious forms of encephalitis.

Nuclear Myocardial Perfusion Imaging Versus Stress Echocardiography in the Preoperative Evaluation of Patients for Kidney Transplantation.

UNLABELLED: The goal of this study was to evaluate the diagnostic accuracy, cost-effectiveness, and appropriate use of SPECT myocardial perfusion imaging (SMPI) versus stress echocardiography in the preoperative evaluation of patients for kidney transplantation. METHODS: A single-institution, retrospective study was performed. SMPI was performed with regadenoson and stress echocardiography predominantly with dobutamine. Findings on subsequent coronary angiography were correlated. A cost analysis for SMPI versus stress echocardiography was modeled using reimbursements from the Center for Medicare Services. RESULTS: One hundred thirteen patients underwent imaging (53 SMPI and 60 stress echocardiography). One hundred percent of SMPI studies were diagnostic, compared with only 80% (48/60) in the stress echocardiography group, and this result was statistically significant (χ(2) = 7.96, P < 0.01). The most common reason for a nondiagnostic test was not reaching the target heart rate. In the SMPI group, 15% (8/53) of patients had ischemia on imaging and all underwent subsequent coronary angiography, which confirmed obstructive coronary lesions. One patient with a negative SMPI result underwent a subsequent angiogram that was negative. In the stress echocardiography group, 5% (3/60) of patients had ischemia on imaging and 2 underwent subsequent angiography, which was negative. Three of 12 patients with nondiagnostic examinations underwent further testing. One patient underwent a follow-up positive SMPI scan but no subsequent coronary angiography. The other 2 patients underwent coronary angiography, which was negative. Of the 45 negative stress echocardiography patients, 6 (13%) underwent angiography, with a positive result for obstructive coronary artery disease in 3 of 6. For the modeling of cost analysis, rates of $1,173 and $1,521 (Center for Medicare Services) were used for SMPI and stress echocardiography, respectively. The model assumed that all nondiagnostic imaging would be referred for further stress testing (i.e., nondiagnostic stress echocardiography would be referred for SMPI). This model estimated that initial noninvasive testing with stress echocardiography versus SMPI resulted in a 50% greater cost. CONCLUSION: For the preoperative evaluation of kidney transplantation, SMPI is more often diagnostic than stress echocardiography. A cost model estimates that initial noninvasive diagnostic testing with stress echocardiography would result in an approximately 50% greater cost than SMPI. Our data also suggest that SMPI has greater diagnostic accuracy than stress echocardiography. Therefore, this single-institution experience supports SMPI as the more appropriate test.

Age and Obesity are Independent Predictors of Bile Duct Injuries in Patients Undergoing Laparoscopic Cholecystectomy.

INTRODUCTION: Iatrogenic bile duct injury is a serious complication of cholecystectomy. The aim of this study was to assess predictors of bile duct injury using a national database. METHODS: The Nationwide Inpatient Sample (2010-2012) was queried for laparoscopic cholecystectomy. We used a) diagnoses for bile duct injury and b) bile duct injury repair procedure codes as a surrogate marker for bile duct injuries. RESULTS: A total of 1,015 patients had bile duct injury. The mean age was 58.2 ± 19.7 years, 53.5 % were males, and median Charlson co-morbidity score was 2 [2, 3]. Multivariate analysis revealed morbid obesity [2.8 (2.1-4.3); p = 0.03] and age >65 [1.5 (1.05-2.1); p = 0.01] as the independent predictors for bile duct injury in patients undergoing cholecystectomy. CONCLUSION: Our study finds a new association between obesity, aging, and bile duct injuries which has never been reported in literature before.

Temperature profiles of different cooling methods in porcine pancreas procurement.

Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. This study examines the effect of four different cooling Methods on core porcine pancreas temperature (n = 24) and histopathology (n = 16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all three cooling Methods. Surface cooling alone (Method A) gradually decreased core pancreas temperature to <10 °C after 30 min. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15-20 °C within the first 2 min of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (P = 0.36). Histological scores were different between the cooling Methods (P = 0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (P = 0.02) and Methods A and D (P = 0.02), but not between Methods C and D (P = 0.95), which may highlight the importance of early cooling using an intraductal infusion. In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and histopathology scores. These data may also have implications on human pancreas procurement as use of an intraductal infusion is not common practice.

Magnetic resonance imaging: a tool to monitor and optimize enzyme distribution during porcine pancreas distention for islet isolation.

Porcine islet xenotransplantation is emerging as a potential alternative for allogeneic clinical islet transplantation. Optimization of porcine islet isolation in terms of yield and quality is critical for the success and cost-effectiveness of this approach. Incomplete pancreas distention and inhomogeneous enzyme distribution have been identified as key factors for limiting viable islet yield per porcine pancreas. The aim of this study was to explore the utility of magnetic resonance imaging (MRI) as a tool to investigate the homogeneity of enzyme delivery in porcine pancreata. Traditional and novel methods for enzyme delivery aimed at optimizing enzyme distribution were examined. Pancreata were procured from Landrace pigs via en bloc viscerectomy. The main pancreatic duct was then cannulated with an 18-g winged catheter and MRI performed at 1.5-T. Images were collected before and after ductal infusion of chilled MRI contrast agent (gadolinium) in physiological saline. Regions of the distal aspect of the splenic lobe and portions of the connecting lobe and bridge exhibited reduced delivery of solution when traditional methods of distention were utilized. Use of alternative methods of delivery (such as selective re-cannulation and distention of identified problem regions) resolved these issues, and MRI was successfully utilized as a guide and assessment tool for improved delivery. Current methods of porcine pancreas distention do not consistently deliver enzyme uniformly or adequately to all regions of the pancreas. Novel methods of enzyme delivery should be investigated and implemented for improved enzyme distribution. MRI serves as a valuable tool to visualize and evaluate the efficacy of current and prospective methods of pancreas distention and enzyme delivery.

Gallstone pancreatitis: a review.

Gallstone disease is the most common cause of acute pancreatitis in the Western world. In most cases, gallstone pancreatitis is a mild and self-limiting disease, and patients may proceed without complications to cholecystectomy to prevent future recurrence. Severe disease occurs in about 20% of cases and is associated with significant mortality; meticulous management is critical. A thorough understanding of the disease process, diagnosis, severity stratification, and principles of management is essential to the appropriate care of patients presenting with this disease. This article reviews these topics with a focus on surgical management, including appropriate timing and choice of interventions.

Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer.

Although cancer-mediated changes in hemostatic proteins unquestionably promote hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are less well defined. The goals of the present investigation were to determine if plasma obtained from patients with breast, lung, pancreas and colon cancer was less or more susceptible to lysis by tissue-type plasminogen activator (tPA) compared to plasma obtained from normal individuals. Archived plasma obtained from patients with breast (n = 18), colon/pancreas (n = 27) or lung (n = 19) was compared to normal individual plasma (n = 30) using a thrombelastographic assay that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples were activated with tissue factor/celite, had tPA added, and had data collected until clot lysis occurred. Additional, similar samples had potato carboxypeptidase inhibitor added to assess the role played by thrombin-activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than inflicting a hypofibrinolytic state, the three groups of cancers demonstrated increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of lysis, decreased clot lysis time). However, hypercoagulation manifested as increased speed of clot formation and strength compensated for enhanced fibrinolytic vulnerability, resulting in a clot residence time that was not different from normal individual thrombi. In sum, enhanced hypercoagulability associated with cancer was in part diminished by enhanced fibrinolytic vulnerability to tPA.

Colon and pancreas tumors enhance coagulation: role of hemeoxygenase-1.

Colon and pancreatic cancer are associated with significant thrombophilia. Colon and pancreas tumor cells have an increase in hemeoxygenase-1 (HO-1) activity, the endogenous enzyme responsible for carbon monoxide production. Given that carbon monoxide enhances plasmatic coagulation, we determined if patients undergoing resection of colon and pancreatic tumors had an increase in endogenous carbon monoxide and plasmatic hypercoagulability. Patients with colon (n = 17) and pancreatic (n = 10) tumors were studied. Carbon monoxide was determined by the measurement of carboxyhemoglobin (COHb). A thrombelastographic method to assess plasma coagulation kinetics and formation of carboxyhemefibrinogen (COHF) was utilized. Nonsmoking patients with colon and pancreatic tumors had abnormally increased COHb concentrations of 1.4 ± 0.9 and 1.9 ± 0.7%, respectively, indicative of HO-1 upregulation. Coagulation analyses comparing both tumor groups demonstrated no significant differences in any parameter; thus the data were combined for the tumor groups for comparison with 95% confidence interval values obtained from normal individuals (n = 30) plasma. Seventy percent of tumor patients had a velocity of clot formation greater than the 95% confidence interval value of normal individuals, with 53% of this hypercoagulable group also having COHF formation. Further, 67% of tumor patients had clot strength that exceeded the normal 95% confidence interval value, and 56% of this subgroup had COHF formation. Finally, 63% of all tumor patients had COHF formation. Future investigation of HO-1-derived carbon monoxide in the pathogenesis of colon and pancreatic tumor-related thrombophilia is warranted.

Panresistant cytomegalovirus in a kidney transplant recipient.

Cytomegalovirus (CMV) is an important pathogen often encountered after solid organ transplantation and is associated with increased morbidity and mortality. Resistance of CMV to antiviral agents is becoming more common but with few treatment strategies. Two specific mutations in the CMV genome--the UL97 and UL54 genes--correlate with antiviral drug resistance. We describe a 49-year-old, CMV-seronegative woman who received a CMV-seropositive donor kidney transplant and appropriate CMV prophylaxis. Approximately 1 month after transplantation, the patient developed CMV viremia that responded to valganciclovir. She was later diagnosed with recurrent CMV infection, CMV resistance, and both the UL97 and UL54 gene mutations. The patient responded to foscarnet and significant reduction of immunosuppression; she was negative for CMV viremia for the next 12 months. This case illustrates the importance of having heightened awareness for the possibility of panresistant CMV early and decreasing immunosuppression as the cornerstone of treatment.

Early liver retransplantation in adults.

Up to 23% of liver allografts fail post-transplant. Retransplantation is only the recourse but remains controversial due to inferior outcomes. The objective of our study was to identify high-risk periods for retransplantation and then compare survival outcomes and risk factors. We performed an analysis of United Network for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through 2011. We analyzed the records of 49,288 recipients; of those, 2714 (5.5%) recipients were retransplanted. Our analysis included multivariate regression with the outcome of retransplantation. The highest retransplantation rates were within the first week (19% of all retransplantation, day 0-7), month (20%, day 8-30), and year (33%, day 31-365). Only retransplantation within the first year (day 0-365) had below standard outcomes. The most significant risk factors were as follows: within the first week, cold ischemia time >16 h [odds ratio (OR) 3.6]; within the first month, use of split allografts (OR 2.9); and within the first year, use of a liver donated after cardiac death (OR 4.9). Each of the three high-risk periods within the first year had distinct causes of graft failure, risk factors for retransplantation, and survival rates after retransplantation.

Robotic-assisted cystogastrostomy for a patient with a pancreatic pseudocyst.

Pancreatic pseudocysts are generally treated by endoscopic cystogastrostomy. However, difficult cases involving abscess, necrosis, or risk of hemorrhage often require surgical intervention. Here, we report a case of a robotically assisted cystogastrostomy. The patient presented with an infected pseudocyst with adjacent varices. Use of the da Vinci Surgical System allowed us to create a widely patent anastomosis between the pseudocyst and the stomach. The patient tolerated the procedure well without any complications. This report demonstrates the feasibility of robotic cystogastrostomy.

Recognition of complications after pancreaticoduodenectomy for cancer determines inpatient mortality.

CONTEXT: While perioperative mortality after pancreaticoduodenectomy is decreasing, key factors remain to be elucidated. OBJECTIVE: The purpose of this study was to investigate inpatient mortality after pancreaticoduodenectomy in the Nationwide Inpatient Sample (NIS), a representative inpatient database in the USA. METHODS: Patient discharge data (diagnostic and procedure codes) and hospital characteristics were investigated for years 2009 and 2010. The inclusion criteria were a procedure code for pancreaticoduodenectomy, elective procedure, and a pancreatic or peripancreatic cancer diagnosis. Chi-square test determined statistical significance. A logistic regression model for mortality was created from significant variables. RESULTS: Two-thousand and 958 patients were identified with an average age of 65±12 years; 53% were male. The mean length of stay was 15±12 days with a mortality of 4% and a complication rate of 57%. Eighty-six percent of pancreaticoduodenectomy occurred in teaching hospitals. Pancreaticoduodenectomy performed in teaching hospitals in the first half of the academic year were associated with higher mortality than in the latter half (5.5% vs. 3.4%, P=0.005). On logistic regression analysis, non-surgical complications are the largest predictor of death (P<0.001) while operations in the latter half of the academic year are associated with decreased mortality (P<0.01). CONCLUSIONS: The timing of pancreaticoduodenectomy for cancer remained more predictive of mortality than age or length of stay; only complications were more predictive of death than time of year. This suggests that there remains a clinically and statistically significant learning curve for trainees in identifying complications; further study is needed to prove that identification of complications leads to a decrease in mortality rate by taking corrective actions.

A critical analysis of early death after adult liver transplants.

INTRODUCTION: The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high-risk periods and to incorporate cause of death into the analysis of post-transplant survival. METHODS: We performed a retrospective analysis on United Network for Organ Sharing data for all adult recipients of liver transplants from January 1, 2002 to October 31, 2011. Our analysis included multivariate logistic regression where the primary outcome measure was patient death of 49,288 recipients. RESULTS: The highest mortality rate by day post-transplant was on day 0 (0.9%). The most significant risk factors were as follows: for one-d mortality from technical failure, intensive care unit admission odds ratio (OR 3.2); for one-d mortality from graft failure, warm ischemia >75 min (OR 5.6); for one-month mortality from infection, a previous transplant (OR 3.3); and for one-month mortality from graft failure, a previous transplant (OR 3.7). CONCLUSION: We found that the highest mortality rate after liver transplantation is within the first day and the first month post-transplant. Those two high-risk periods have common, as well as different, risk factors for mortality.