Outcomes of liver transplant recipients with high MELD scores: an experience from a Canadian centre.

BACKGROUND: The frequency with which patients with high Model for End-Stage Liver Disease (MELD) scores undergo liver transplantation has been increasing. Canadian literature regarding the outcomes of liver transplantation in recipients with high MELD scores is limited. The primary objective of this study was to assess patient and graft survival among recipients with high (> 35) and low (≤ 35) MELD scores. Secondary objectives were to potentially identify independent predictors of graft failure and patient mortality. METHODS: We conducted a retrospective chart review of patients undergoing liver transplantation at a single Canadian centre from 2012 to 2017. RESULTS: A total of 332 patients were included in the study: 280 patients had a MELD score of 35 or lower, and 52 had a MELD score above 35. Patients with high MELD scores had higher rates of pretransplant acute kidney injury and dialysis (p < 0.001), admission to the intensive care unit (ICU) or intubation (p < 0.001), intraoperative blood product transfusions (p < 0.001) and post-transplantation acute kidney injury and dialysis (p < 0.001), as well as longer ICU (p < 0.001) and hospital stays (p = 0.002). One- and 3-year patient survival in recipients with MELD scores of 35 or lower was 93.1% and 84.9% versus 85.0% and 80.0% in recipients with MELD scores above 35 (p = 0.37). One- and 3-year graft survival in recipients with MELD scores of 35 or lower was 91.7% and 90.9% versus 77.2% and 72.8% in recipients with MELD scores above 35 (p < 0.001). Prior liver transplant was an independent predictor of patient mortality, and no independent predictors of graft failure were identified. When MELD was replaced with D-MELD (donor age × recipient MELD), it predicted graft failure but not patient survival. CONCLUSION: No difference in patient mortality was found between MELD groups. Graft survival was significantly lower in recipients with MELD scores above 35. D-MELD may potentially be used as an adjunct in determining risk of graft failure in recipients with high MELD scores.

The association between bacterobilia and the risk of postoperative complications following pancreaticoduodenectomy.

BACKGROUND: Pre-operative biliary bacterial colonisation (bacterobilia) is considered a risk factor for infectious complications after pancreaticoduodenectomy (PD). This study aimed to investigate the role of the PD biliary microbiome grown in the development of post-PD complications. METHODS: In a retrospective study of 162 consecutive patients undergoing PD (2008-2018), intra-operative bile cultures were analyzed and sensitivities compared to pre-anesthetic antibiotics and thirty-day post-surgery complications. RESULTS: Bacterobilia was present in 136 patients (84%). Most bile cultures grew bacteria resistant to pre-operative antibiotics (n = 112, 82%). Patients with bacterobilia had significantly higher rates of major complication than patients without (P = 0.017), as well as higher rates of surgical-site infections (SSI) (P = 0.010). Patients with negative bile cultures (n = 26) had significantly lower rates of major complication and SSI than those growing sensitive (n = 24) or non-sensitive (n = 112) bacteria (major complication P = 0.029 and SSI P = 0.011). CONCLUSION: Positive bile cultures were associated with a higher incidence of major complications and SSI. Patients with sterile bile cultures had the lowest risk of post-operative complications and efforts to reduce rates of bacterobilia, such as limitation of biliary instrumentation, should be considered. Sensitivity to antibiotics had no effect upon the rate of post-operative complications, but this may reflect low cohort numbers.

Minimally invasive hepatectomy is associated with decreased morbidity and resource utilization in the elderly.

BACKGROUND: The aim of this study was to evaluate whether elderly patients undergoing elective hepatectomy experience increased morbidity/mortality and whether these outcomes could be mitigated by minimally invasive hepatectomy (MIH). METHODS: 15,612 patients from 2014 to 2017 were identified in the Hepatectomy Targeted Procedure Participant Use File of the American College of Surgeons National Surgical Quality Improvement Program. Multivariable logistic regression models were constructed to examine the effect of elderly status (age ≥ 75 years, N = 1769) on outcomes with a subgroup analysis of elderly only patients by open (OH) versus MIH (robotic, laparoscopic, and hybrid, N = 4044). Propensity score matching was conducted comparing the effect of MIH to OH in elderly patients to ensure that results are not the artifact of imbalance in baseline characteristics. RESULTS: Overall, elderly patients had increased risk for 30-day mortality, major morbidity, prolonged length of hospital stay, and discharge to destination other than home. In the elderly subgroup, MIH was associated with decreased major morbidity (OR 0.71, P = 0.031), invasive intervention (OR 0.61, P = 0.032), liver failure (OR 0.15, P = 0.011), bleeding (OR 0.46, P < 0.001), and prolonged length of stay (OR 0.46, P < 0.001). Propensity score-matched analyses successfully matched 4021 pairs of patients treated by MIH vs. OH, and logistic regression analyses on this matched sample found that MIH was associated with decreased major complications (OR 0.69, P = 0.023), liver failure (OR 0.14, P = 0.010), bile leak (OR 0.46, P = 0.009), bleeding requiring transfusion (OR 0.46, P < 0.001), prolonged length of stay (OR 0.46, P < 0.001), and discharge to destination other than home (OR 0.691, P = 0.035) compared to OH. CONCLUSION: MIH is associated with decreased risk of major morbidity, liver failure, bile leak, bleeding, prolonged length of stay, and discharge to destination other than home among elderly patients in this retrospective study. However, MIH in elderly patients does not protect against postoperative mortality.

Precision medicine and gut dysbiosis.

Clostridioides difficile Infection (CDI) is a leading cause of healthcare-associated infections in Canada, affecting the gastrointestinal tract which can lead to fever, abdominal pain, and diarrhea. Effective treatment for patients with Recurrent CDI (rCDI) can be achieved by Fecal Microbiota Transplantation (FMT) by introducing the gut micro-organisms of a healthy person (donor) into the bowel of the affected individual. Research has shown that an increase in the specific bacterial phyla post-FMT may be partly responsible for this gut restoration and elimination of disease. Furthermore, in understanding the key bacteria associated with successful FMT, full treatment plans can be developed for the individual needs of the patient by matching an infected individual with a donor possessing ideal microbiota for the specific patient. This development of precision medicine and more systematic adoption of FMT can be the next step toward more rapid resolution of rCDI.

Recipient characteristics and morbidity and mortality after liver transplantation.

BACKGROUND AND AIMS: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. We sought to identify an easily applicable set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within five years after liver transplantation. METHODS: We collected national (n = 31,829, 2002-2015) and center-specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95% CI 1.48-1.72); recipient age >60 years (three patients; HR 1.29; 95% CI 1.23-1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16-1.37); diabetes (two patients; HR 1.20; 95% CI 1.14-1.27); or serum creatinine ≥1.5 mg/dl without hemodialysis (two patients; HR 1.15; 95% CI 1.09-1.22). RESULTS: Graft survival within five years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with >8 points, graft survival was 42% (model for end-stage liver disease [MELD] score <25) and 50% (MELD score 25-35) in recipients receiving grafts from donors with a donor risk index >1.7. In center-specific data within the first year, subjects with ≥5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p <0.01), higher admissions for rehabilitation (12.3% vs. 2.7%, p <0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p <0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p = 0.03) within five years. CONCLUSION: The impact of co-morbidities in an MELD-based organ allocation system need to be reassessed. The proposed clinical tool may be helpful for center-specific assessment of risk of graft failure in non-HCV patients and for discussion regarding relevant morbidity in selected subsets. LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60 years, ventilator status, diabetes, hemodialysis and creatinine >1.5 mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival.

Risk factors for early readmission after total pancreatectomy and islet auto transplantation.

BACKGROUND: Little published data exist examining causes of hospital readmission following total pancreatectomy with islet autotransplantation (TPIAT). METHODS: A retrospective analysis was performed of a prospectively collected institutional TPIAT database. Primary outcome was unplanned readmission to the hospital within 30 days from discharge. Reasons and risk factors for readmission as well as islet function were evaluated and compared by univariate and multivariate analysis. RESULTS: 83 patients underwent TPIAT from 2006 to 2014. 21 patients (25.3%) were readmitted within 30 days. Gastrointestinal problems (52.4%) and surgical site infection (42.8%) were the most common reasons for readmission. Initial LOS and reoperation were risk factors for early readmission. Patients with delayed gastric emptying (DGE) were three times more likely to get readmitted. In multivariate analysis, patients undergoing pylorus preservation surgery were nine times more likely to be readmitted than the antrectomy group. CONCLUSION: Early readmission after TPIAT is common (one in four patients), underscoring the complexity of this procedure. Early readmission is not detrimental to islet graft function. Patients undergoing pylorus preservation are more likely to get readmitted, perhaps due to increased incidence of delayed gastric emptying. Decision for antrectomy vs. pylorus preservation needs to be individualized.

Significance of measured intraoperative portal vein flows after thrombendvenectomy in deceased donor liver transplantations with portal vein thrombosis.

Adequate portal vein (PV) flow in liver transplantation is essential for a good outcome, and it may be compromised in patients with portal vein thrombosis (PVT). This study evaluated the impact of intraoperatively measured PV flow after PV thrombendvenectomy on outcomes after deceased donor liver transplantation (DDLT). The study included 77 patients over a 16-year period who underwent PV thrombendvenectomy with complete flow data. Patients were classified into 2 groups: high PV flow (>1300 mL/minute; n = 55) and low PV flow (≤1300 mL/minute; n = 22). Postoperative complications and graft survival were analyzed according to the PV flow. The 2 groups were similar in demographic characteristics. Low PV flow was associated with higher cumulative rates of biliary strictures (P = 0.02) and lower 1-, 2-, and 5-year graft survival (89%, 85%, and 68% versus 64%, 55%, and 38%, respectively; P = 0.002). There was no difference in the incidence of postoperative PVT between the groups (1.8% versus 9.1%; P = 0.19). No biliary leaks or hepatic artery thromboses were reported in either group. By multivariate analyses, age >60 years (hazard ratio [HR], 3.04, 95% confidence interval [CI], 1.36-6.82; P = 0.007) and low portal flow (HR, 2.31; 95% CI, 1.15-4.65; P = 0.02) were associated with worse survival. In conclusion, PV flow <1300 mL/minute after PV thrombendvenectomy for PVT during DDLT was associated with higher rates of biliary strictures and worse graft survival. Consideration should be given to identifying reasons for low flow and performing maneuvers to increase PV flow when intraoperative PV flows are <1300 mL/minute. Liver Transplantation 23 1032-1039 2017 AASLD.

Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

BACKGROUND & AIMS: Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial. METHODS: We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 mL, via enema, from healthy anonymous donors; n = 38) or placebo (50 mL water enema; n = 37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the Data Monitoring and Safety Committee, but all patients already enrolled in the trial were allowed to complete the study. RESULTS: Seventy patients completed the trial (3 dropped out from the placebo group and 2 from the FMT group). Nine patients who received FMT (24%) and 2 who received placebo (5%) were in remission at 7 weeks (a statistically significant difference in risk of 17%; 95% confidence interval, 2%-33%). There was no significant difference in adverse events between groups. Seven of the 9 patients in remission after FMT received fecal material from a single donor. Three of the 4 patients with UC ≤1 year entered remission, compared with 6 of 34 of those with UC >1 year (P = .04, Fisher's exact test). Stool from patients receiving FMT had greater microbial diversity, compared with baseline, than that of patients given the placebo (P = .02, Mann-Whitney U test). CONCLUSIONS: FMT induces remission in a significantly greater percentage of patients with active UC than placebo, with no difference in adverse events. Fecal donor and time of UC appear to affect outcomes. ClinicalTrials.gov Number: NCT01545908.

Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention. OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada. INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%. RESULTS: A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups. CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.

Prevention and treatment of liver allograft antibody-mediated rejection and the role of the 'two-hit hypothesis'.

PURPOSE OF REVIEW: The review outlines the diagnosis, prevention strategies, and possible treatment options for acute and chronic antibody-mediated rejection (AMR). RECENT FINDINGS: Although rare, severe acute AMR (aAMR) usually occurs in patients with high mean fluorescence intensity despite serial dilutions or high-titer preformed class I donor-specific alloantibodies (DSA). The diagnosis is suspected when allograft dysfunction occurs with DSA, diffuse C4d staining, and a microvascular injury, and may be aided by the aAMR score. However, the incidence of and treatment approach to combined T-cell-mediated rejection (TCMR) with DSA present and some but not all features of AMR is yet to be determined. Chronic liver allograft AMR is characterized by low-grade chronic inflammation and progressive fibrosis with DSA, the chronic AMR (cAMR) score may facilitate diagnosis. The 'two-hit' hypothesis, whereby a coexistent insult upregulates human leukocyte antigen class II target antigens on the microvascular endothelium, may explain why suboptimal donors with lower sensitization levels might suffer from acute AMR and those with chronic complications (e.g., recurrent original disease) might be more susceptible to chronic AMR. Although treatment algorithms are needed, prevention is preferable and at a minimum includes transfusion minimization, and medication adherence. SUMMARY: Severe acute AMR is rare but diagnosable, and there is need to determine the incidence of and optimal therapy for less severe combined AMR and TCMR. Chronic AMR is likely more common and of significant relevance to long-term allograft survival improvement. The two-hit hypothesis may help to explain the rarity of both findings and shed insight onto future prevention and treatment strategies.

Improved long-term outcomes after resection of pancreatic adenocarcinoma: a comparison between two time periods.

BACKGROUND: Despite reduced perioperative mortality and routine use of adjuvant therapy following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), improvement in long-term outcome has been difficult to ascertain. This study compares outcomes in patients undergoing resection for PDAC within a single, high-volume academic institution over two sequential time periods. METHODS: Retrospective review of patients with resected PDAC, in two cohorts: period 1 (P1), 1991-2000; and period 2 (P2), 2001-2010. Univariate and multivariate analyses using the Cox proportional hazards model were performed to determine prognostic factors associated with long-term survival. Survival was evaluated using Kaplan-Meier analyses. RESULTS: A total of 179 pancreatectomies were performed during P1 and 310 during P2. Perioperative mortality was 6.7 % (12/179) in P1 and 1.6 % (5/310) in P2 (p = 0.003). P2 had a greater number of lymph nodes resected (17 [0-50] vs. 7 [0-31]; p < 0.001), and a higher lymph node positivity rate (69 % [215/310] vs. 58 % [104/179]; p = 0.021) compared with P1. The adjuvant therapy rate was 30 % (53/179) in P1 and 63 % (195/310) in P2 (p < 0.001). By multivariate analysis, node and margin status, tumor grade, adjuvant therapy, and time period of resection were independently associated with overall survival (OS) for both time periods. Median OS was 16 months (95 % confidence interval [CI] 14-20) in P1 and 27 months (95 % CI 24-30) in P2 (p < 0.001). CONCLUSIONS: Factors associated with improved long-term survival remain comparable over time. Short- and long-term survival for patients with resected PDAC has improved over time due to decreased perioperative mortality and increased use of adjuvant therapy, although the proportion of 5-year survivors remains small.

Long-term follow-up of biliary complications after adult right-lobe living donor liver transplantation.

INTRODUCTION: Long-term biliary complications after living donor liver transplantation (LDLT) are not well described in the literature. This study was undertaken to determine the long-term impact of biliary complications after adult right-lobe LDLT. METHODS: This retrospective review analyzed an 11-yr experience of 344 consecutive right-lobe LDLTs with at least two yr of follow-up. RESULTS: Biliary leaks occurred in 50 patients (14.5%), and strictures occurred in 67 patients (19.5%). Cumulative biliary complication rates at 1, 2, 5, and 10 yr were 29%, 32%, 36%, and 37%, respectively. Most early biliary leaks were treated with surgical drainage (N = 29, 62%). Most biliary strictures were treated first with endoscopic retrograde cholangiography (42%). There was no association between biliary strictures and the number of ducts (hazard ratio [HR] 1.017 [0.65-1.592], p = 0.94), but freedom from biliary stricture was associated with a more recent era (2006-2010) (HR 0.457 [0.247-0.845], p = 0.01). Long-term graft survival did not differ between those who had or did not have biliary complications (66% vs. 67% at 10 yr). CONCLUSIONS: Biliary strictures are common after LDLT but may decline with a center's experience. With careful follow-up, they can be successfully treated, with excellent long-term graft survival rates.

Inferior vena cava reconstruction for leiomyosarcoma of Zone I-III requiring complete hepatectomy and bilateral nephrectomy with autotransplantation.

The inferior vena cava (IVC) is the most common site of leiomyosarcomas arising from a vascular origin. Leiomyosarcomas of the IVC are categorized by anatomical location. Zone I refers to the infrarenal portion of the IVC, Zone II from the hepatic veins to the renal veins, and Zone III from the right atrium to the hepatic veins. This is a rare presentation of a Zone I-III leiomyosarcoma. Fifty-two-years-old female with a medical history significant only for HTN was admitted to the hospital with bilateral lower extremity edema and dyspnea. Two-dimensional echo demonstrated a right atrial thrombus, extending into the IVC. On subsequent CT and MRI, a 15 cm mass was noted that began in the right atrium and extended into the IVC, with continuation below the renal veins to above the level of the confluence of the common iliac veins. The patient underwent a complete resection of the mass, replacement of the IVC with Dacron graft, total hepatectomy and bilateral nephrectomy, with liver and kidney autotransplantation. Pathology was consistent with a high grade spindle cell sarcoma of vena cava origin. Patient was readmitted approximately 4 weeks postoperatively to begin adjuvant chemotherapy. This case represents a zone I-III IVC leiomyosarcoma treated with surgical R0 resection. This included a hepatectomy, bilateral nephrectomy, and hepatic and left renal autotransplantation. These complex tumors should be treated with surgical resection, and require a multidisciplinary approach.

Impact of viral hepatitis on outcomes after liver resection for hepatocellular carcinoma: results from a north american center.

BACKGROUND: Hepatitis B (HBV) and hepatitis C (HCV) are well-recognized risk factors for hepatocellular carcinoma (HCC). The characteristics and clinical outcomes of HCC arising from these conditions may differ. This study was conducted to compare the outcomes of HCC associated with HBV and HCV after liver resection. METHODS: Of 386 liver resections for HCC performed between July 1992 and April 2011, 181 patients had HBV and 74 patients had HCV. Patients with HBV/HCV coinfections (n = 20), non-HBV/HCV etiology (n = 94), and postoperative death within 3 months (n = 17) were excluded. Patient, tumor characteristics, and perioperative and oncologic outcomes were compared between patients with HBV and HCV. RESULTS: The patients with HBV had better overall survival (OS) than patients with HCV (68 vs. 59 months, p = 0.03); however, there was no difference in recurrence-free survival (RFS) between the groups (44 vs. 45 months, p = 0.1). The factors predictive of OS based on multivariate analyses included: vascular invasion [p < 0.01, hazard ratio (HR) = 3.4], Child-Pugh Score (p < 0.01, HR = 4.8), and underlying liver disease (HCV vs HBV) (p = 0.01, HR = 1.9). Vascular invasion and tumor number (p < 0.01, HR = 2.3 and p < 0.01, HR = 2.1) were independent predictors of RFS. CONCLUSIONS: OS but not RFS after liver resection for HCC is better in patients with HBV than HCV. This survival advantage for HBV patients may be due to differences in tumor biology and outcomes after disease recurrence.

Aberrant right hepatic artery in pancreaticoduodenectomy for adenocarcinoma: impact on resectability and postoperative outcomes.

OBJECTIVES: An aberrant right hepatic artery (aRHA) may pose technical and oncologic challenges during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) as a result of its proximity to the head of the pancreas. The aim of this study was to assess the impact of an aRHA on resectability, and perioperative and oncologic outcomes after PD for PA. METHODS: An 11-year retrospective cohort study was conducted. A total of 289 patients with PA scheduled for PD with intent for resection were included in the study. RESULTS: Of 289 patients, 249 underwent PD and 40 were found to have unresectable tumours. Incidences of aRHA in the resectable (14.9%) and unresectable (7.5%) groups were similar (P = 0.2); the main reasons for aborting PD were not directly related to the presence of an aRHA. In patients who underwent resection, complications occurred more frequently in the standard PD group (41.5% versus 24.3%; P = 0.04), but there was no difference in rates of positive margin (R1) resection (10.8% versus 16.0%; P = 0.4) or median overall survival (17 months versus 23 months; P = 0.1) between patients with and without an aRHA. CONCLUSIONS: The presence of an aRHA in patients with PA does not affect resectability. In patients with resectable tumours, the presence of an aRHA does not increase morbidity or R1 resection rates and does not impact on overall survival.

Ratio of hepatic arterial flow to recipient body weight predicts biliary complications after deceased donor liver transplantation.

OBJECTIVES: Adequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation. METHODS: A retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800). RESULTS: Patients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001). CONCLUSIONS: A ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.

Combined pancreaticoduodenectomy and colon resection for locally advanced peri-ampullary tumours: analysis of peri-operative morbidity and mortality.

BACKGROUND: Combined pancreaticoduodenectomy (PD) and colonic resection may be necessary to achieve an R0 resection of peri-ampullary tumours. The aim of this study was to examine the morbidity and mortality associated with this procedure. METHODS: A retrospective cohort study was performed comparing 607 patients who underwent a standard pancreaticoduodenectomy (S-PD) to 28 patients who had a concomitant colon resection and PD (PD-colon) over a 10-year period at an academic centre. RESULTS: Patients in the PD-colon group were more likely to have received neoadjuvant chemotherapy ± radiation (3/28, 11% versus 14/607, 2%, P = 0.024). Operative time was also longer (530 versus 410 min, P < 0.001) and they were more likely to have had portal vein resections (9/28, 32% versus 76/607, 13%, P = 0.007). There was no difference in the intra-operative blood loss, length of stay, or overall complication rates. The PD-colon group had a higher rate of severe post-operative bleeding (4/28, 11% versus 8/607, 1%, P = 0.002). The post-operative mortality rates for the PD-colon and PD groups were 2/28 (7%) and 8/607 (1%), respectively (P = 0.068). CONCLUSIONS: PD-colon has an acceptable risk of peri-operative morbidity compared with S-PD in well-selected patients.

Thyroid Hormone Levels Correlate With the Maturation of Implanted Pancreatic Endoderm Cells in Patients With Type 1 Diabetes.

BACKGROUND: Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells. In an ongoing clinical trial, PECs implanted in macroencapsulation devices into patients with type 1 diabetes were safe but yielded heterogeneous outcomes. Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells. METHODS: We measured circulating triiodothyronine and thyroxine levels in all patients treated at 1 of the 7 sites of the ongoing clinical trial and determined if thyroid hormone levels were associated with the C-peptide or glucagon levels and cell fate of implanted PECs. RESULTS: Both triiodothyronine and thyroxine levels were significantly associated with the proportion of cells that adopted an insulin-producing fate with a mature phenotype. Thyroid hormone levels were inversely correlated to circulating glucagon levels after implantation, suggesting that thyroid hormones lead PECs to favor an insulin-producing fate over a glucagon-producing fate. In mice, hyperthyroidism led to more rapid maturation of PECs into insulin-producing cells similar in phenotype to PECs in euthyroid mice. CONCLUSION: These data highlight the relevance of thyroid hormones in the context of PEC therapy in patients with type 1 diabetes and suggest that a thyroid hormone adjuvant therapy may optimize cell outcomes in some PEC recipients.