Left Lobe First With Purely Laparoscopic Approach: A Novel Strategy to Maximize Donor Safety in Adult Living Donor Liver Transplantation.

OBJECTIVE: Evaluate outcome of left-lobe graft (LLG) first combined with purely laparoscopic donor hemihepatectomy (PLDH) as a strategy to minimize donor risk. BACKGROUND: An LLG first approach and a PLDH are 2 methods used to reduce surgical stress for donors in adult living donor liver transplantation (LDLT). But the risk associated with application LLG first combined with PLDH is not known. METHODS: From 2012 to 2023, 186 adult LDLTs were performed with hemiliver grafts, procured by open surgery in 95 and PLDH in 91 cases. LLGs were considered first when graft-to-recipient weight ratio ≥0.6%. Following a 4-month adoption process, all donor hepatectomies, since December 2019, were performed laparoscopically. RESULTS: There was one intraoperative conversion to open (1%). Mean operative times were similar in laparoscopic and open cases (366 vs 371 minutes). PLDH provided shorter hospital stays, lower blood loss, and lower peak aspartate aminotransferase. Peak bilirubin was lower in LLG donors compared with right-lobe graft donors (1.4 vs 2.4 mg/dL, P < 0.01), and PLDH further improved the bilirubin levels in LLG donors (1.2 vs 1.6 mg/dL, P < 0.01). PLDH also afforded a low rate of early complications (Clavien-Dindo grade ≥ II, 8% vs 22%, P = 0.007) and late complications, including incisional hernia (0% vs 13.7%, P < 0.001), compared with open cases. LLG was more likely to have a single duct than a right-lobe graft (89% vs 60%, P < 0.01). Importantly, with the aggressive use of LLG in 47% of adult LDLT, favorable graft survival was achieved without any differences between the type of graft and surgical approach. CONCLUSIONS: The LLG first with PLDH approach minimizes surgical stress for donors in adult LDLT without compromising recipient outcomes. This strategy can lighten the burden for living donors, which could help expand the donor pool.

Liquid Biopsy by ctDNA in Liver Transplantation for Colorectal Cancer Liver Metastasis.

INTRODUCTION: Colorectal cancer is a leading cause of cancer-related death worldwide. Metastatic liver disease develops in 50% of cases and drives patient outcomes. Although the ideal treatment for colorectal cancer liver metastases (CRLM) is resection, only a third of patients are suitable for this approach. Reports of liver transplantation in selected patients with unresectable CRLM have shown encouraging results compared to conventional forms of therapy. No study to date has examined the utility of liquid biopsy circulating tumor DNA (ctDNA) for evaluation of residual disease in this cohort of patients. We report a small series of liver transplantation in patients with CRLM in whom ctDNA was assessed peri-operatively. METHODS: Five patients underwent liver transplantation for unresectable CRLM or liver failure following CRLM treatment from 2018 to 2022. Clinical data, cross-sectional imaging, and serum biomarkers including peri-operative ctDNA were reviewed from electronic medical records. RESULTS: All patients are alive without radiologic evidence of disease at time of this publication. Median time of follow-up was 32 months (IQR 6.6-40 months). ctDNA was assessed before (4 patients) and after transplant (6 patients). One patient experienced a pulmonary recurrence that was resected, for whom pre-recurrence ctDNA was not available; the remaining patients have not experienced recurrence. Four patients are without evidence of ctDNA following transplant, and two demonstrate persistent ctDNA positivity post-transplant. Three of four patients with positive pre-transplant ctDNA remain ctDNA-negative post-transplant. CONCLUSIONS: Liver transplantation for liver-confined unresectable CRLM is emerging as a valid surgical option in selected patients. The significance of liquid biopsy in this population remains elusive due to lack of data. The clearance of ctDNA after transplant in these patients with metastatic disease and despite their immunosuppression is notable. The significance and usefulness of liquid biopsy in patient selection, surveillance, and as an indication for treatment warrant further investigation.

The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting.

BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM. METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT." RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively. CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.

Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Demystifying BRAF Mutation Status in Colorectal Liver Metastases : A Multi-institutional, Collaborative Approach to 6 Open Clinical Questions.

OBJECTIVE: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs). BACKGROUND: The clinical implications of mut BRAF status in CRLMs are largely unknown. METHODS: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management. RESULTS: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis. CONCLUSIONS: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis.

Outcomes of Liver Transplantation in Patients With Preexisting Coronary Artery Disease.

BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases.

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. Design, Setting, and Participants: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. Exposures: Hepatectomy. Main Outcomes and Measures: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. Results: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. Conclusions and Relevance: This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

A chronological review of 500 minimally invasive liver resections in a North American institution: overcoming stagnation and toward consolidation.

BACKGROUND: Although interest in expanding the application of minimally invasive liver resection (MILR) is high the world over, most of the extensive experience in MILR has been reported from Far East Asia and Europe and its adoption in North America is limited. The aim of this study was to review the experience of MILR in a single North American institute over a 15-year period, highlighting both the obstacles encountered and strategies adopted to overcome the stagnation in its uptake. METHODS: This study included 500 MILR cases between 2006 and 2020. Patient demographics, disease characteristics, surgical technique, and perioperative outcomes are summarized. The major hepatectomy rate and conversion rate were assessed according to case numbers (first 100, 101-300, and 301-500 cases) to assess chronological trends. RESULTS: Of 500, 402 MILRs were done by pure laparoscopic (80.4%), 67 were hand assisted (13.4%), and 31 were robotic (6.2%). The majority (64%) of cases were performed for malignancy (n = 320; 100 Hepatocellular carcinoma, 153 Colorectal metastases, 27 Intrahepatic cholangiocarcinoma, and others, 40, 64%). A total of 71 cases were converted to open (14.2%). The annual case number gradually increased over the first few years; however, case numbers stayed around 30 between 2009 and 2017. In this period, despite accumulating MILR experience, open conversion rates increased despite no change in major hepatectomy rate. After this period of long-term stagnation, we introduced crucial changes in team composition and laparoscopic instrumentation. Our MILR case number and major hepatectomy rate thereafter increased significantly without increasing conversion or complication rates. CONCLUSION: Our recovery from long-term stagnation by instituting key changes as detailed in this study could be used as a guidepost for programs that are contemplating transitioning their MILR program from minor to advanced resections. Establishing a formal MILR training model through proper mentorship/proctorship and building a dedicated MILR team would be imperative to this strategy.

Validation of the IWATE criteria as a laparoscopic liver resection difficulty score in a single North American cohort.

BACKGROUND: Laparoscopic liver resection (LLR) involves a difficult learning curve, for which multiple difficulty scores have been proposed to assist with safe adaptation. The IWATE Criteria is a 4-level difficulty score shown to correlate with conversion to open surgery, estimated blood loss (EBL), and operative time in Japanese and French cohorts. We set out to validate the IWATE Criteria in a North American cohort, describe the evolution of our LLR program, and analyze the IWATE Criteria's ability to predict conversion to open surgery. METHODS: Patients that underwent LLR between January 2006 and December 2019 were selected from a prospectively maintained database. Difficulty outcomes, including conversion to open surgery, EBL, operative time, and post-operative complications were analyzed according to IWATE difficulty level, both overall and between chronological eras. The IWATE Criteria's ability to predict conversion to open surgery was assessed with a receiver operating characteristic (ROC) analysis. RESULTS: A total of 426 patients met inclusion criteria. Operative time, EBL, and conversion to open surgery increased in concordance with low to advanced IWATE difficulty. ROC analysis for conversion to open surgery demonstrated an overall area under the curve (AUC) of 0.694. Predictive performance was superior during the first two eras, with AUCs of 0.771 and 0.775; predictive value decreased as the LLR program gained experience, with AUCs of 0.708 and 0.551 for eras three and four. CONCLUSIONS: This study validated the IWATE Criteria in a North American population distinct from previous Japanese and French cohorts, based on its correlation with operative time, EBL, and conversion to open surgery. The IWATE Criteria may be of utility for identification of LLR cases appropriate for surgeon experience, as well as determination of laparoscopic feasibility. Interval difficulty score recalibration may be warranted as surgeon perception of difficulty evolves.

The spectrum of histopathological findings after SVR to DAA for recurrent HCV infection in liver transplant recipients.

Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p < 0.001) and in the IFN group (n = 21; p = 0.001) but not in the DAA group (p = 0.093). Of all subjects, 21% had worsening stage, 31% had improvement, and 48% had no change in stage. Of the treatment groups, 27% in the IFN and 17% in the DAA groups had worsening stage; however, the results were not statistically significant in all subjects or by treatment modality. Persistent inflammatory infiltrates and fibrosis was noted in allograft tissue of patients cured with DAA. Significant improvement in grade was noted in the IFN group, without a significant change in stage.

Performance of two prognostic scores that incorporate genetic information to predict long-term outcomes following resection of colorectal cancer liver metastases: An external validation of the MD Anderson and JHH-MSK scores.

INTRODUCTION: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status were developed: modified CRS (mCRS) and GAME score. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS. METHODS: Patients undergoing hepatectomy for CRLM (2000-2018) in 10 centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrell's C-index and Akaike's Information Criterion. RESULTS: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14 405, 14 447, and 14 319, respectively. CONCLUSION: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.

Neuroendocrine liver metastases: The role of liver transplantation.

PURPOSE OF REVIEW: Neuroendocrine tumor (NET) metastasis localized to the liver is an accepted indication for liver transplantation as such tumors have a low biological aggressiveness in terms of malignancy and are slow growing. RECENT FINDINGS: The long-term results are comparable with and in some cases even better than those of transplantations performed for primary liver cancer. However, compared with nonmalignant conditions, neuroendocrine liver metastasis (NELM) may result in an inferior outcome of transplantation. In the face of the scarcity of donated organs and recent improved results of non-surgical treatment for NELM, controversy over patient selection and timing for liver transplantation continues. SUMMARY: In this review, we provide an overview of the diagnostic work-up and selection criteria of patients with NELM being considered for liver transplantation. Thereafter, we provide a critical analysis of the reported outcomes of OLT.

Conditional probability of graft survival in liver transplantation using donation after circulatory death grafts - a retrospective study.

The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P < 0.01). Actual, 1-, and 3-year conditional HR of 1-year GS in DCD compared to DBD livers were 1.87, 1.49, and 1.39, respectively. Graft loss analyses showed that those lost to biliary related complications were significantly higher in the DCD group even 3 years after LT. National registry data demonstrate the protracted higher risks inherent to DCD liver grafts in comparison to their DBD counterparts, despite survival through the early period after LT. These findings underscore the importance of judicious DCD graft selection at individual center level to minimize the risk of long-term biliary complications.

The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study.

BACKGROUND AND OBJECTIVES: Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established. METHODS: Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature. RESULTS: A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs. CONCLUSION: The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.

The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis.

OBJECTIVE: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status. BACKGROUND: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors. METHODS: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status. RESULTS: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38). CONCLUSIONS: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.

Should We Be Utilizing More Liver Grafts From Pediatric Donation After Circulatory Death Donors? A National Analysis of the SRTR from 2002 to 2017.

BACKGROUND: Rates of withdrawal of life-sustaining treatment are higher among critically ill pediatric patients compared to adults. Therefore, livers from pediatric donation after circulatory death (pDCD) could improve graft organ shortage and waiting time for listed patients. As knowledge on the utilization of pDCD is limited, this study used US national registry data (2002-2017) to estimate the prognostic impact of pDCD in both adult and pediatric liver transplant (LT). METHODS: In adult LT, the short-term (1-year) and long-term (overall) graft survival (GS) between pDCD and adult donation after circulatory death (aDCD) grafts was compared. In pediatric LT, the short- and long-term prognostic outcomes of pDCD were compared with other type of grafts (brain dead, split, and living donor). RESULTS: Of 80 843 LTs in the study, 8967 (11.1%) were from pediatric donors. Among these, only 443 were pDCD, which were utilized mainly in adult recipients (91.9%). In adult recipients, short- and long-term GS did not differ significantly between pDCD and aDCD grafts (hazard ratio = 0.82 in short term and 0.73 in long term, both P > 0.05, respectively). Even "very young" (≤12 y) pDCD grafts had similar GS to aDCD grafts, although the rate of graft loss from vascular complications was higher in the former (14.0% versus 3.6%, P < 0.01). In pediatric recipients, pDCD grafts showed similar GS with other graft types whereas waiting time for DCD livers was significantly shorter (36.5 d versus 53.0 d, P < 0.01). CONCLUSIONS: Given the comparable survival seen to aDCDs, this data show that there is still much scope to improve the utilization of pDCD liver grafts.