Persistent hyperbilirubinemia following preoperative biliary stenting in patients undergoing anatomic hepatectomy predicts serious complications.

BACKGROUND: Biliary obstruction before liver resection is a known risk factor for post-operative complications. The aim of this study was to determine the impact of persistent hyperbilirubinemia following preoperative biliary drainage before liver resection. METHODS: The ACS-NSQIP (2016-2021) database was used to extract patients with cholangiocarcinoma who underwent anatomic liver resection with preoperative biliary drainage comparing those with persistent hyperbilirubinemia (> 1.2 mg/dL) to those with resolution. Patient characteristics and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including persistent hyperbilirubinemia to evaluate their independent effect on serious complications, liver failure, and mortality. RESULTS: We evaluated 463 patients with 217 (46.9%) having hyperbilirubinemia (HB) despite biliary stenting. Bivariate analysis demonstrated that patients with HB had a higher rate of serious complications than those with non-HB (80.7% vs 70.3%; P = 0.010) including bile leak (40.9% vs 31.8%; P = 0.045), liver failure (26.7% vs 17.9%; P = 0.022), and bleeding (48.4% vs 36.6%; P = 0.010). Multivariable analysis demonstrated that persistent HB was independently associated with serious complications (OR 1.88, P = 0.020) and mortality (OR 2.39, P = 0.049) but not post-operative liver failure (OR 1.65, P = 0.082). CONCLUSIONS: Failed preoperative biliary decompression is a predictive factor for post-operative complications and mortality in patients undergoing hepatectomy and may be useful for preoperative risk stratification.

Long-term outcomes after normothermic machine perfusion in liver transplantation-Experience at a single North American center.

Normothermic machine perfusion (NMP) has emerged as a valuable tool in the preservation of liver allografts before transplantation. Randomized trials have shown that replacing static cold storage (SCS) with NMP reduces allograft injury and improves graft utilization. The University of Alberta's liver transplant program was one of the early adopters of NMP in North America. Herein, we describe our 7-year experience applying NMP to extend preservation time in liver transplantation using a "back-to-base" approach. From 2015 to 2021, 79 livers were transplanted following NMP, compared with 386 after SCS only. NMP livers were preserved for a median time of minutes compared with minutes in the SCS cohort (P < .0001). Despite this, we observed significantly improved 30-day graft survival (P = .030), although there were no differences in long-term patient survival, major complications, or biliary or vascular complications. We also found that although SCS time was strongly associated with increased graft failure at 1 year in the SCS cohort (P = .006), there was no such association among NMP livers (P = .171). Our experience suggests that NMP can safely extend the total preservation time of liver allografts without increasing complications.

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years.

OBJECTIVE: To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation. SUMMARY BACKGROUND DATA: Studies describing long-term outcomes with ITx and PTx are scarce. METHODS: We included adults undergoing ITx (n=266) and PTx (n=146) at the University of Alberta from January 1999 to October 2019. Outcomes include patient and graft survival, insulin independence, glycemic control, procedure-related complications, and hospital readmissions. Data are presented as medians (interquartile ranges, IQR) and absolute numbers (percentages, %) and compared using Mann-Whitney and χ2 tests. Kaplan-Meier estimates, Cox proportional hazard models and mixed main effects models were implemented. RESULTS: Crude mortality was 9.4% and 14.4% after ITx and PTx, respectively ( P= 0.141). Sex-adjusted and age-adjusted hazard-ratio for mortality was 2.08 (95% CI, 1.04-4.17, P= 0.038) for PTx versus ITx. Insulin independence occurred in 78.6% and 92.5% in ITx and PTx recipients, respectively ( P= 0.0003), while the total duration of insulin independence was 2.1 (IQR 0.8-4.6) and 6.7 (IQR 2.9-12.4) year for ITx and PTx, respectively ( P= 2.2×10 -22 ). Graft failure ensued in 34.2% and 19.9% after ITx and PTx, respectively ( P =0.002). Glycemic control improved for up to 20-years post-transplant, particularly for PTx recipients (group, P= 7.4×10 -7 , time, P =4.8×10 -6 , group*time, P= 1.2×10 -7 ). Procedure-related complications and hospital readmissions were higher after PTx ( P =2.5×10 -32 and P= 6.4×10 -112 , respectively). CONCLUSIONS: PTx shows higher sex-adjusted and age-adjusted mortality, procedure-related complications and readmissions compared with ITx. Conversely, insulin independence, graft survival and glycemic control are better with PTx. This study provides data to balance risks and benefits with ITx and PTx, which could improve shared decision-making.

Examining the equity and diversity characteristics of academic general surgeons hired in Canada.

BACKGROUND: Job competition and underemployment among surgeons emphasize the importance of equitable hiring practices. The purpose of this study was to describe some of the demographic characteristics of academic general surgeons and to evaluate the gender and visible minority (VM) status of those recently hired. METHODS: Demographic information about academic general surgeons across Canada including gender, VM status, practice location and graduate degree status was collected. Location of residency was collected for recently hired general surgeons (hired between 2013 and 2020). Descriptive statistics were performed on the demographic characteristics at each institution. Pearson correlation coefficients and hypothesis testing were used to determine the correlation between various metrics and gender and VM status. RESULTS: A total of 393 general surgeons from 30 academic hospitals affiliated with 14 universities were included. The percentage of female general surgeons ranged from 0% to 47.4% and the percentage of VM general surgeons ranged from 0% to 66.7% at the hospitals. This heterogeneity did not correlate with city population (gender: r = 0.06, p = 0.77; VM: r = 0.04, p = 0.83). The percentage of VM general surgeons at each hospital did not correlate with the percentage of VM population in the city (r = 0.13, p = 0.49). Only 34 of 120 recently hired academic general surgeons (28.3%) did not have a graduate degree. The percentage of recently hired academic general surgeons who did not have a graduate degree was approximately 1.5 times higher among male hirees than female hirees. With respect to academic promotion, the percentage of female full professors ranged from 0% to 40.0% and did not correlate with the percentage of female general surgeons at each institution (r = 0.11, p = 0.70). The percentage of VM full professors ranged from 0% to 44.4% and was moderately correlated with the percentage of VM surgeons at each institution (r = 0.40, p = 0.16). CONCLUSION: The academic general surgery workforce appears to be somewhat diverse. However, there was substantial heterogeneity in diversity between hospitals, leaving room for improvement. We must be willing to examine our hiring processes and be transparent about them to build an equitable surgical workforce.

Gender Differences in Authorship Among Transplant Physicians: Are We Bridging the Gap?

BACKGROUND: Despite an increase in the number of practicing female physicians, gender disparities in academic medicine persist. For investigating gender gap in the transplantation field, this study examined the relationship between gender and authorship among medical and surgical transplant physicians. MATERIALS AND METHODS: In this observational study, all original clinical science articles published in the journals of Transplantation, American Journal of Transplantation, and Clinical Transplantation were reviewed from January 2008 to December 2017. Chi-square analysis was used to compare the proportions of female and male authors, and the Cochrane-Armitage test was used for comparisons over time. RESULTS: A total of 2530 publications and 2988 individual authors met the inclusion criteria for the study. Male physicians published significantly more articles compared to female physicians as first (67.4% versus 30.4%) and senior authors (82.9% versus 16.2%), respectively. There were increases in the proportion of female first and senior authors between 2008 and 2017. The majority of authors with multiple publications were male (73.6%), specifically male medical physicians (44.3%). Male medical physicians were the most productive in publication amount and authorship positions. CONCLUSIONS: While research activity among female physicians increased over time, gender disparity continues to exist among female and male physicians in the transplantation field. Academic activity is lower among females in publication amount and authorship positions. These trends emphasize the need to identify barriers to female physician academic productivity within the transplantation field.

Public health service increased risk donor kidney grafts for transplant into children, a survey of pediatric nephrologists.

BACKGROUND: Kidney transplant is the best treatment for end-stage renal disease (ESRD); however, access is limited by severe organ shortage. Public Health Service increased risk donors (PHS-IRD) represent a significant portion of available organs which are discarded at disproportional rates. METHODS: Pediatric nephrologists were surveyed regarding PHS-IRD kidneys to understand attitudes and perceived barriers to the use of these grafts in children. We sought to elucidate what methods may help increase the likelihood of PHS-IRD acceptance. RESULTS: Twenty-two responses were received from United States pediatric nephrologists representing 11 UNOS regions (response rate 5.9%). Of respondents, 50% had been practicing for 20+ years, 77% in academic hospitals, and 63% in cities with over 1 000 000 people. All respondents worked in an institution with a kidney transplant program. 41% reported that they would not accept PHS-IRD kidneys under any circumstance, 45% would accept depending on the candidate's medical status, and 14% routinely accepted PHS-IRD kidneys. Infectious transmission was the biggest disincentive reported (59%), with only 55% of respondents feeling comfortable counseling families on the associated risks. 82% of respondents did not perceive all PHS-IRD as the same, and 90% supported stratifying PHS-IRD into tiers based on risk, which would increase the likelihood of organ acceptance (82%) and assist in counseling families (91%). CONCLUSIONS: With improved utilization, PHS-IRD kidneys offer a step toward decreasing the organ shortage. These findings suggest hesitance in use of PHS-IRD kidneys for pediatric recipients. Further stratification of risk could aid in provider organ acceptance and counseling patients.

Gender differences in authorship among Hepato-pancreatico-biliary surgeons.

BACKGROUND: While studies have explored the gender gap in scientific publications, no study has investigated surgical literature in much detail. We examined the gender gap in Hepato-pancreato-biliary publications over the last decade. METHODS: All physician authored original clinical science articles published in HPB, Annals of Surgery, Surgery, Annals of Surgical Oncology, and JAMA Surgery were reviewed from 2008 to 2017. Chi square analysis was used to compare the proportions of female and male authors and Cochrane-Armitage test was used for comparisons over time. RESULTS: Of the 1067 publications, 84.0% of all authorships were held by men. Women physicians made up 10.3% of senior and 21.4% of first authorships with increased representation from 2.13% in 2007 to 14.8% in 2017 (p = 0.001). Women physicians comprised 14.1% of senior authors in JAMA Surgery, but only 2.46% in Annals of Surgical Oncology. Male authors were five times more likely to publish multiple articles compared to their female counterparts. Female first authors progressed to senior authors at a rate of 1.13% versus 5.73% for male authors (p = 0.89). CONCLUSION: These findings elucidate the continued underrepresentation of women in senior research roles and the need to recruit and mentor women in all stages of their academic careers.

Safe Cholecystectomy Multi-society Practice Guideline and State of the Art Consensus Conference on Prevention of Bile Duct Injury During Cholecystectomy.

BACKGROUND: BDI is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI. METHODS: Literature reviews were conducted for 18 key questions across 6 broad topics around cholecystectomy directed by a steering group and subject experts from 5 surgical societies (Society of Gastrointestinal and Endoscopic Surgeons, Americas Hepato-Pancreato-Biliary Association, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, and European Association for Endoscopic Surgery). Evidence-based recommendations were formulated using the grading of recommendations assessment, development, and evaluation methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus. RESULTS: Consensus was reached on 17 of 18 questions by the guideline development group and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team. CONCLUSIONS: These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.

Safe cholecystectomy multi-society practice guideline and state-of-the-art consensus conference on prevention of bile duct injury during cholecystectomy.

BACKGROUND: Bile duct injury (BDI) is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI. METHODS: Literature reviews were conducted for 18 key questions across six broad topics around cholecystectomy directed by a steering group and subject experts from five surgical societies (SAGES, AHPBA IHPBA, SSAT, and EAES). Evidence-based recommendations were formulated using the GRADE methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus. RESULTS: Consensus was reached on 17 of 18 questions by the Guideline Development Group (GDG) and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team. CONCLUSION: These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.

A 22-year experience with pancreatic resection for metastatic renal cell carcinoma.

BACKGROUND: The pancreas is a rare site of metastases, although metastatic renal cell carcinoma (mRCC) is the most commonly reported secondary tumor. Pancreatectomy has been described in selected patients with localized metastases, but long-term benefit remains poorly defined. METHODS: A retrospective review of a prospectively maintained database was performed to evaluate the outcomes of patients undergoing pancreatectomy for mRCC at a tertiary care center from 1995-2017. Postoperative complications were evaluated using the Modified Accordion Grading System (MAGS) and Kaplan-Meier curves and log-rank tests were utilized for survival analysis. RESULTS: 29 patients underwent pancreatectomy for mRCC including 15 distal pancreatectomies (DP), 10 pancreaticoduodenectomies (PD) and 4 total-pancreatectomies (TP). The mean age was 67 ± 8 years, and 15 were male. The median time from index nephrectomy to pancreatectomy was 8 (IQR: 3.72-12.2) years. There was no 90 Day post-pancreatectomy mortalities and the morbidity incidence included 13 Minor MAGS and 8 Severe MAGS complications respectively. Post-pancreatectomy disease specific survival at 2- and 4-years were 89% and 80% with 12 patients being alive at last follow up. CONCLUSIONS: Pancreatic resection can be safely performed in select patients with localized mRCC with favorable long-term outcomes.

Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.

Background: In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types. This study was conducted to determine the impact of these susceptibility antigens on islet allograft survival. Methods: This is a single-centre retrospective cohort study. This cohort of transplant recipients (n = 268) received islets from 661 donor pancreases between March 11th, 1999 and August 29th, 2018 at the University of Alberta Hospital (Edmonton, AB, Canada). The frequency of the Type 1 diabetes susceptibility HLA antigens (HLA-A24, -B39, -DQ8, -DQ2 and-DQ2-DQA1∗05) in recipients and donors were determined. Recipient and donor HLA antigens were examined in relation to time to first C-peptide negative status/graft failure or last observation point. Taking into account multiple transplants per patient, we fitted a Gaussian frailty survival analysis model with baseline hazard function stratified by transplant number, adjusted for cumulative islet dose and other confounders. Findings: Across all transplants recipients of donors positive for HLA-DQ8 had significantly better graft survival (adjusted HRs 0.33 95% CI 0.17-0.66; p = 0.002). At first transplant only, donors positive for HLA-DQ2-DQA1∗05 had inferior graft survival (adjusted HR 1.96 95% CI 1.10-3.46); p = 0.02), although this was not significant in the frailty analysis taking multiple transplants into account (adjusted HR 1.46 95% CI 0.77-2.78; p = 0.25). Other HLA antigens were not associated with graft survival after adjustment for confounders. Interpretation: Our findings suggest islet transplantation from HLA-DQ8 donors is associated with superior graft outcomes. A donor positive for HLA-DQ2-DQA1∗05 at first transplant was associated with inferior graft survival but not when taking into account multiple transplants per recipient. The relevance of HLA-antigens on organ allocation needs further evaluation and inclusion in islet transplant registries and additional observational and interventional studies to evaluate the role of HLA-DQ8 in islet graft survival are required. Funding: None.

Evaluating Islet Cell Isolation and Transplantation From Donors Following Medical Assistance in Dying.

Background: Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors. Methods: ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023. Differences of isolated islet equivalents (IEQs), numeric viability and other quantitative in vitro metabolic measures were assessed. Results: Overall, 81 ICIs were available of whom 34 (42%) and 47 (58%) from MAiD and DCD-III, respectively. There were no differences of pancreas and digested tissue weight and islets viability among the 2 groups; however, cold ischemic time was longer in MAiD (11.5 versus 9.1 h; P = 0.021). The IEQ (P < 0.001) and percent trapped (P < 0.001) were higher in the DCD-III; however, MAiD islets demonstrated a higher purity (P = 0.020). Overall, 15 ITx were performed of whom 3 (8.8%) and 12 (25.5%) from MAiD and DCD-III, respectively (P = 0.056). Patients had a median fasting C-peptide of 0.51 ng/mL (interquartile range, 0.30-0.76 nmol/L), with no differences between groups (MAiD = 0.52 versus DCD-III = 0.51; P = 0.718). The median HbA1c was 6.2% (interquartile range, 5.7%-7%) (MAiD = 6.3% versus DCD-III = 6.1%; P = 0.815) and BETA2 scores (MAiD = 7.4 versus DCD-III = 12.8; P = 0.229) did not differ. Conclusions: ICI from MAiD donor pancreas may be successfully transplanted with comparable outcomes to DCD-III and may be used for research. These results justify additional efforts to consider MAiD as another valuable source of grafts for ITx. Further multicenter studies and larger clinical experience are needed to validate our findings.

Periductal Stromal Tumor of the Breast with a TERT Promoter Mutation: First Case Report with Comprehensive Molecular Analysis.

The molecular pathogenesis of breast fibroepithelial tumors continues to be elucidated. Recently, highly recurrent MED12 mutations arising in exon 2 at codon 44 were discovered in fibroadenomas and phyllodes tumors. In addition, a high prevalence of TERT promoter mutations in two hotspots (124 and 126 bp upstream from the translation start site) was discovered in up to 65% of phyllodes tumors. Breast periductal stromal tumors are a potentially distinct category of fibroepithelial lesions that are exceptionally rare with controversial classification and pathogenesis. Herein, we report the first comprehensive molecular genetic workup of a breast periductal stromal tumor that harbored a TERT promoter -124C > T mutation, supporting a relation to phyllodes tumors.

COVID-19 Infection and Acute Pancreas Transplant Graft Thrombosis.

The coronavirus disease 2019 (COVID-19) pandemic created an unprecedented challenge for healthcare, and the world continues to struggle in recovering from its aftermath. COVID-19 has been clearly linked to hypercoagulable states and can lead to end-organ ischemia, morbidity, and mortality. Immunosuppressed solid organ transplant recipients represent a highly vulnerable population for the increased risk of complications and mortality. Early venous or arterial thrombosis with acute graft loss after whole pancreas transplantation is well-described, but late thrombosis is rare. We herein report a case of acute, late pancreas graft thrombosis at 13 years post pancreas-after-kidney (PAK) transplantation coinciding with an acute COVID-19 infection in a previously double-vaccinated recipient.

C-peptide Targets and Patient-centered Outcomes of Relevance to Cellular Transplantation for Diabetes.

BACKGROUND: C-peptide levels are a key measure of beta-cell mass following islet transplantation, but threshold values required to achieve clinically relevant patient-centered outcomes are not yet established. METHODS: We conducted a cross-sectional retrospective cohort study evaluating patients undergoing islet transplantation at a single center from 1999 to 2018. Cohorts included patients achieving insulin independence without hypoglycemia, those with insulin dependence without hypoglycemia, and those with recurrent symptomatic hypoglycemia. Primary outcome was fasting C-peptide levels at 6 to 12 mo postfirst transplant; secondary outcomes included stimulated C-peptide levels and BETA-2 scores. Fasting and stimulated C-peptide and BETA-2 cutoff values for determination of hypoglycemic freedom and insulin independence were evaluated using receiver operating characteristic curves. RESULTS: We analyzed 192 patients, with 122 (63.5%) being insulin independent without hypoglycemia, 61 (31.8%) being insulin dependent without hypoglycemia, and 9 (4.7%) experiencing recurrent symptomatic hypoglycemia. Patients with insulin independence had a median (interquartile range) fasting C-peptide level of 0.66 nmol/L (0.34 nmol/L), compared with 0.49 nmol/L (0.25 nmol/L) for those being insulin dependent without hypoglycemia and 0.07 nmol/L (0.05 nmol/L) for patients experiencing hypoglycemia ( P < 0.001). Optimal fasting C-peptide cutoffs for insulin independence and hypoglycemia were ≥0.50 nmol/L and ≥0.12 nmol/L, respectively. Cutoffs for insulin independence and freedom of hypoglycemia using stimulated C-peptide were ≥1.2 nmol/L and ≥0.68 nmol/L, respectively, whereas optimal cutoff BETA-2 scores were ≥16.4 and ≥5.2. CONCLUSIONS: We define C-peptide levels and BETA-2 scores associated with patient-centered outcomes. Characterizing these values will enable evaluation of ongoing clinical trials with islet or stem cell therapies.

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study.

BACKGROUND: Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. METHODS: This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. RESULTS: Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1-3 mo post-first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. CONCLUSIONS: Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.