Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.

Recurrence-free survival dynamics following adjuvant chemotherapy for resected colorectal cancer: A systematic review of randomized controlled trials.

BACKGROUND: Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. METHODS: The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. RESULTS: The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010). CONCLUSIONS: In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.

Pancreatectomy for intraductal papillary mucinous neoplasm: has anything changed in North America?

BACKGROUND: Multiple guidelines on the management of intraductal papillary mucinous neoplasm (IPMN) have been published over the past decade. However, practice data are lacking. This study aims to determine whether pancreatectomy procedures, IPMN pathology, or outcomes have changed. METHODS: ACS-NSQIP Procedure Targeted Pancreatectomy database was queried for patients with IPMN from 2014 to 2019. Cases were stratified by pathology, tumor stage/cyst size and procedure. Pancreatectomies for IPMN by year, 30-day morbidity, and clinically relevant postoperative pancreatic fistula (CR-POPF) were quantified. Mann-Kendall trend tests were performed to assess surgical trends and associated outcomes over time. RESULTS: 3912 patients underwent pancreatectomy for IPMN. 21% demonstrated malignancy and 79% were benign. Morbidity and mortality occurred in 29.7% and 1.5% of cases, respectively. Over time, no change was observed in use of pancreatectomy for IPMN (10%) or in benign/malignant pathology, or cyst size. Robotic approach increased from 9.1% to 16.5% with decreases in laparoscopic (19.5%-15.0%) and open interventions (71.5%-68.1%, p = 0.016). No change was observed over time in morbidity or mortality; however, rates of CR-POPF decreased (18.8%-13.8%, p < 0.001). CONCLUSIONS: Practice patterns in treatment of IPMN have not changed significantly in North America. More patients are undergoing robotic pancreatectomy, and postoperative pancreatic fistula rates are improving.

Demographic inequities exist and influence transplant outcomes in liver transplantation for acute alcohol-associated hepatitis.

BACKGROUND: Liver transplantation has inherent disparities but data is scarce in liver transplant (LT) candidates with acute alcohol-associated hepatitis (AAH). We aimed to investigate demographic inequities and its impact on survival outcomes among AAH LT candidates. METHODS: A retrospective analysis using the United Network of Organ Sharing database was conducted between 2000 and 2021. 25 981 LT recipients with alcohol-associated liver cirrhosis and 662 recipients with AAH were included. Waitlisted candidates were also evaluated. RESULTS: In comparison with alcohol-associated liver cirrhosis, AAH LT recipients were more likely Asian or "other" race and younger. Hispanics demonstrated better graft and patient survival (p < 0.05) but were less likely to be waitlisted and transplanted for AAH than for liver cirrhosis. Women with AAH were more likely to be waitlisted and transplanted. Pre-existing diabetes and male sex were associated with higher graft failure (25% and 8% respectively). Increasing recipient age were 2% more likely to experience negative outcomes. Chronicity of liver disease did not impact graft (p = 0.137) or patient survival (p = 0.145). CONCLUSION: Our results revealed demographic factors have a significant impact on transplant listing, organ allocation and survival outcomes. Further investigations are imperative to minimize disparities in LT evaluation and provide equity in healthcare.

Ethnic and Racial Diversity Among Surgeon and Non-Surgeon Deans of Allopathic Medical Schools.

INTRODUCTION: Previous publications have assessed the diversity among medical students, residents, faculty, and department leaders in surgery and medicine overall. We aim to evaluate the diversity among medical school deans in the United States. We quantify and compare the representation of women and underrepresented minority surgeon and non-surgeons. METHODS: 151 allopathic medical schools were included. Data regarding demographics, education, training, and previous leadership position were collected from institutional websites, online resources, and July 2021 Association of American Medical Colleges Council of Deans. Demographics for surgeon and non-surgeon were compared using chi square and logistic regression with 5% significance interval. RESULTS: 21.9% (n = 33) of all medical school deans were surgeons. 21.2% (n = 7) were women, which was not significantly different from non-surgeons (22%, P = .92). All the women surgeons were non-Hispanic white, similar to all deans (P = .83). 78.8% (n = 26) of all surgeon deans were non-Hispanic White compared to 84.7% (n = 100) overall (P = .28). There were 13 Black deans, four of whom were surgeons, and only one Hispanic dean, who was not a surgeon. Surgeons were more likely to be fellows of their professional society (P = .012). CONCLUSION: The demographic diversity of surgeon and non-surgeon US medical school deans is not significantly different. The deficiencies in leadership diversity in medicine persists among medical school deans. There remains substantial room to improve the representation of women and underrepresented minorities as deans.

The Use of Vasopressors During Deceased Donor Pancreas Procurement Decreases the Risk of Pancreas Transplant Graft Failure.

OBJECTIVES: The objective of this study was to identify the effect of various vasopressors on pancreas graft failure and patient survival. METHODS: A retrospective analysis of the United Network for Organ Sharing database was performed between 2000 and 2019. Patient and graft survival rates were analyzed up to 5 years posttransplant. RESULTS: The data included 17,348 pancreas transplant recipients: 12,857 simultaneous pancreas-kidney, 1440 pancreas transplant alone, and 3051 pancreas-after-kidney transplant recipients. Use of dopamine during deceased donor procurement increased graft failure by 18% (hazard ratio [HR], 1.18; P < 0.001). Absence of vasopressor caused graft failure to rise by 8% (HR, 1.08; P = 0.09). Dopamine increased the mortality rate by 37% (HR, 1.37; P < 0.001) and the absence of vasopressor increased the mortality rate by 14% (HR, 1.14; P = 0.02). Phenylephrine and norepinephrine reduced the mortality rate by 10% (HR, 0.90; P = 0.05) and 11% (HR, 0.89; P = 0.10), respectively. CONCLUSIONS: The absence of vasopressor use or the use of dopamine is associated with a higher risk of both pancreas transplant graft failure and recipient mortality. The use of phenylephrine and norepinephrine reduces the risk of mortality. This information should guide deceased donor hemodynamic support management in anticipation of pancreas procurement for future transplantation.

Liver transplantation does not increase morbidity or mortality in women undergoing surgery for breast cancer.

PURPOSE: The incidence of breast cancer following solid organ transplantation is comparable to the age-matched general population. The rate of de novo breast cancer following liver transplantation varies. Furthermore, there is limited information on the management and outcomes of breast cancer in liver transplant recipients. We aim to evaluate the impact of liver transplantation on breast cancer surgery outcomes and compare the outcomes after breast cancer surgery in liver transplant recipient in transplant versus non-transplant centers. METHODS: National Inpatient Sample database was accessed to identify liver transplant recipient with breast cancer. Mortality, complications, hospital charges, and total length of stay were evaluated with multivariate logistic regression testing. Weighted multivariate regression models were employed to compare outcomes at transplant and non-transplant centers. RESULTS: Ninety-nine women met inclusion criteria for liver transplantation + breast cancer and were compared against women with breast cancer without liver transplantation (n = 736,527). Liver transplantation + breast cancer had lower performance status as confirmed via higher Elixhauser Comorbidity Index (20.5% vs 10.2%, p < 0001). There were significantly more complications in the liver transplantation cohort when compared to the non-liver transplant recipient (15.0% vs 8.2%, p = 0.012). However, on multivariate analysis, liver transplantation was not an independent risk factor for post-operative complications following breast cancer surgery (odd ratio, 1.223, p = 0.480). Cost associated with breast cancer care was significantly higher in those with liver transplantation (2.621, p < 0.001). Breast conservation surgery in liver transplantation had shorter length of stay as compared to breast cancer alone (odds ratio, 0.568, p = 0.027) in all hospitals. CONCLUSION: Liver transplantation does not increase short-term mortality when undergoing breast cancer surgery. Although there were significantly more complications in the liver transplantation cohort when compared to the non-liver transplant recipient (15.0% vs 8.2%, p = 0.012), on multivariate analysis, liver transplantation was not an independent risk factor for postoperative complications following breast cancer surgery. Breast cancer management in liver transplant recipient at non-transplant centers incurred higher charges but no difference in complication rate or length of stay when compared to transplant centers.

Preemptive renal transplant: too early is not always better-a national cohort study.

BACKGROUND: Preemptive renal transplants (PRT) confer better outcomes than renal transplants performed after initiation of hemodialysis. PRTs are occurring at progressively higher residual recipient renal function. METHODS: We evaluated donor, recipient, and transplant characteristics of 26,384 preemptive transplants between 2010 and 2019 using the United Network of Organ Sharing (UNOS) database. Recipients of PRTs were divided into four distinct groups depending upon the glomerular filtration rate (GFR) (GFR [Formula: see text] 10, 10 < GFR [Formula: see text] 15, 15 < GFR [Formula: see text] 19 and > 19, ml/min/1.73 m2) at the time of transplant. We followed graft and patient survival for five years and assessed donor, recipient, and transplant characteristics such as race, gender, and type of insurance. RESULTS: PRTs occurring at GFR > 19 ml/min (early preemptive renal transplants, ePRT) from live and deceased donors were not associated with improved graft nor patient survival compared to the other preemptive transplants. PRTs occurring at GFR range of 10-15 ml/min conferred the best graft survival. Black donor-recipient pairs were 54% less likely to be involved in ePRT, while non-Hispanic White donor-recipient pairs were 20% more likely to receive ePRT. CONCLUSION: ePRT represents misallocation of valuable organ resources and a waste of native renal function. There is no evidence that ePRT is associated with superior graft or patient survival compared to the other preemptive transplants. Conversely, ePRT produces poorer graft and patient survival outcomes compared to the other PRTs. GFR range of 10-15 ml/min is optimal and associated with superior outcomes.

Diversity in American Society of Transplant Surgeons Governance: Equitable but Unequal.

OBJECTIVES: The diversity in the governance of the American Society of Transplant Surgeons has not been described. We aimed to quantify the present state of its leadership as a baseline to inform future research. MATERIALS AND METHODS: Lists of leaders on the American Society of Transplant Surgeons Council, the COVID-19 Strike Force, and 20 different American Society of Transplant Surgeons committees were obtained from the Society's website. Demographic and training information for the members were compiled through internet searches and analyzed. RESULTS: The American Society of Transplant Surgeons Council included 15 members, with 20% women. It was 93.3% non-Hispanic White. The COVID-19 Strike Force included 12 surgeons, 16.7% of whom were female, with 75% non-Hispanic White. Of the 198 committee members, 23.7% were women, 68.7% were nonHispanic White, 16.6% were Asian, 8.1% were Hispanic, and 6.6% were Black. Among female committee members, underrepresented minorities comprised 23.6%. Committee chairs included 23% women, 23% underrepresented minorities, and 2.3% minority women. International medical graduates were more likely men (P = .02). CONCLUSIONS: Representation of women in the American Society of Transplant Surgeons leadership has kept pace with their membership in the transplant surgery workforce. There is a deficiency of female under - represented minorities in leadership positions at the Society. Further interventions are required to recruit underrepresented minorities to transplant surgery, catalog their footprint in the workforce, and champion their role as leaders within the American Society of Transplant Surgeons.

Diversity among transplant surgery fellowship program directors: a call to action.

BACKGROUND: The diversity among general surgery residency, HPB and other fellowship program directors has been previously analyzed. However, the diversity in abdominal transplant surgery fellowship program directors remains unknown. METHODS: Abdominal transplant fellowship programs and the corresponding program directors were identified from the American Society of Transplant Surgeons website. Demographic and training information for the members was compiled through internet searches and analyzed. RESULTS: 72 program directors were included. 83.33% were male. 63.9% were non-Hispanic White, 25% were Asian, along with 5.56% Hispanic and Black each. Male program directors were more likely to be Associate Professor (p = 0.041), while females were more likely to be Assistant Professor (p = 0.021). 66% of female program directors were non-Hispanic White. CONCLUSION: Transplant surgery fellowship programs are primarily led by male and non-Hispanic White surgeons. Female representation as leaders is on par with their membership in the transplant surgery workforce. There is a deficiency of both male and female underrepresented minorities in program director positions.

Transplant surgery departmental leaders do not represent workforce demographics especially among women and underrepresented minorities - A retrospective analysis.

INTRODUCTION: The diversity among surgical directors for liver, kidney, and pancreas transplant departments has not been previously evaluated. We aim to quantify the sex and racial demographics of transplant department leaders and assess the impact on patient outcomes. METHODS: Demographics were collected for 116 liver, 192 kidney, and 113 pancreas transplant directors using Organ Procurement and Transplantation Network (OPTN) directory and program websites. Scientific Registry of Transplant Recipients (SRTR) 5-tier program outcomes rankings were obtained for each program and matched to leader demographics. A retrospective analysis of transplant recipients from 2010 to 2019 was performed using the United Network for Organ Sharing (UNOS) database. RESULTS: 91.5% of transplant surgical directors were male. 55% of departments had a Non-Hispanic White leader. Asian, Hispanic and Black transplant chiefs were at the helm of 23.3%, 9%, and 5% of divisions respectively. Multivariate cox regression analysis did not identify any differences in patient outcomes by transplant director demographics. CONCLUSION: There is a paucity of female and URM leaders in transplant surgery. Initiatives to promote research, mentorship, and career advancement opportunities for women and URM are necessary to address the current leadership disparity.

Disparate Formulations for Machine Perfusion: A Survey of Organ Procurement Organizations' Medication Additives and Outcome Analyses.

OBJECTIVES: Machine perfusionfor kidney preservation is a common practice. There is no consensus on the best formula for perfusion solutions. We aimed to discern the additives that organ procurement organizations in the United States include in their perfusate and the impact of these additives on transplant outcomes. MATERIALS AND METHODS: A telephone survey of all 58 organ procurement organizations in the United States regarding additives to their perfusion solutions was conducted. The survey data were merged with transplant recipient outcome data from the United Network for Organ Sharing database.The final analysis included perfused kidneys between January 2014 and March 2019. Logistic regressions were performed to investigate whether a particular perfusion formula was associated with delayed graft function, primary nonfunction, or early graft failure. RESULTS: Additives correlated with decreased rates of graft failure were mannitol in all kidneys and kidneys of lower quality (P < .01) and penicillin/ampicillin in all kidneys (P < .05). Additives associated with increased graft failure regardless of type included verapamil in all kidneys (P < .05) and kidneys of lower quality (P < .01) and arginine with glutathione in all kidneys and low-quality kidneys alone (P < .01). CONCLUSIONS: Further outcomes research and standardized guidelines for additives in machine perfusion of kidneys across all organ procurement organizations are needed.

Kidney transplant surgical director training: Urologists represent a functional alternative to general surgeons.

INTRODUCTION: Kidney transplant (KT) directors are general surgeons or urologists. All KT centers must meet established performance standards. However, it has not been established if general surgery and urology led programs have disparate outcomes. METHODS: Transplant outcomes and donor-recipient characteristics by director training were investigated. Organ Procurement and Transplantation Network (OPTN) directory, program websites were analyzed for surgical director demographics. Scientific Registry of Transplant Recipients (SRTR) 1-year kidney survival and deceased donor (DD) wait-time rankings were evaluated. A retrospective analysis of 142 157 KT recipients from 2010 to 2019 was performed using the United Network for Organ Sharing (UNOS) database. RESULTS: One hunderd and seventy three (90.6%) KT programs were led by general surgeons. There were no significant differences in gender, ethnicity, region, credentials, or fellowship completion. Recipients undergoing KT with urology led programs were older (P = .002) and had longer wait-times (P < .001). These centers used higher KDPI (.47 vs. .45, P < .001) and higher HLA mismatch (3.92 vs. 3.89, P = .02) kidneys. Urology led centers utilized living donors less frequently (32.1% vs. 35.8%, P < .001) and had longer CIT (15.44 vs. 12.21, P < .001). Both had similar SRTR ranking of 1-year survival and DD wait-time. CONCLUSION: Most directors were general surgeon. Patient outcomes did not differ by transplant director training. Urologists represent a viable option for KT leadership and recruitment should be encouraged.