Evaluation of Four Lymph Node Classifications for the Prediction of Survival in Hilar Cholangiocarcinoma

Background An important prognostic indicator of hilar cholangiocarcinoma (HCCA) in patients after surgery is metastasis of lymph nodes (LN). However, there are many types of LN staging systems to the issue of a better determination of the prognosis of patients through the lymphatic staging system which needs research. Based on the above, we tried to re-evaluate the staging system of HCCA LNs. We compared the American Joint Committee on Cancer (AJCC), number of metastatic LNs (MLN), ratio of LN (LNR), and log odds of MLNs (LODDS) in individuals undergoing curative resection to determine the best LN staging system. Methods In the current study, we retrospectively analyzed 229 patients undergoing curative resection. We evaluated the impact of the stage of AJCC pN, LNR, LODDS, and MLN on OS (overall survival) and RFS (recurrence-free survival). According to the curve of receiver operating characteristic (ROC), we compared the predictive capacity of different staging systems of LN for survival and recurrence. Results Multivariate analysis results revealed that LODDS > − 0.45 (95% CI = 1.115–2.709, P = 0.015; 95% CI = 1.187–2.780, P = 0.006) are independent risk factors affecting OS and RFS, respectively. Compared with LN status, AJCC pN stage, MLN, and LNR, the variable having the highest area under the ROC curve (AUC) was LODDS when predicting 1-year, 3-year, and 5-year OS and RFS. Conclusion This study shows that metastasis of LNs is a key indicator for predicting patient death and recurrence. Among them, LODDS is the best LN staging system for the prognostic evaluation of HCCA patients after surgery. Clinicians can incorporate LODDS into HCCA patient lymphatic staging system for a more accurate prognosis of HCCA patients post-surgery.

O-L09 Determining the Prognostic Utility of Immuno-histochemically detected Trans-membranous Human Equilibriative Nucleoside Transporter 1 (hENT1) in Patients Undergoing Hilar Cholangiocarcinoma Resection

Background Human equilibriative nucleoside transporter protein 1 (hENT1) is a trans-membranous protein which facilitates nucleoside transport in to the cell. Immunohistochemically-detected hENT1 abundance is increased in cholangiocarcinoma tumour cells compared to matched non-tumour cells and increased in highly metabolising cells. The privately-held Mackey 10D7G2 hybridoma has demonstrated prognostic utility in Pancreatic Ductal Adenocarcinoma patients. The commercially available Proteintech Polyclonal hENT1 antibody’s prognostic utility has not been previously assessed. Cellular Ki67 expression has been linked to mitotic indices of tumour proliferation. This proof-of-concept study aims to assess the antibodies prognostic utility for hilar cholangiocarcinoma patients undergoing surgical resection. Methods Between February 2009 and February 2016 54 patients underwent resection for peri-hilar cholangiocarcinoma. Formalin-Fixed Paraffin Embedded (FFPE) blocks from a sub-set of 44 resected specimens were retrieved. Appropriate areas of tumour were sampled from the blocks and a Tissue-Matched Array (TMA) was constructed. The TMA underwent staining for each antibody. H-scores were utilised to determine intensity of expression. Correlation of expression between antibodies was determined by Pearson correlation co-efficient and Chi-squared where appropriate. Silencing RNA transfected HepG2 cell-lines was used to determine hENT1 staining by the Proteintech antibody. Demographic and survival characteristics for the patients were acquired from a prospectively held database linked to Hospital Episode Statistics. Survival characteristics were calculated with global log-rank calculations. Results There was significant correlation between the Mackey 10D7G2 and the Proteintech antibodies (p < 0.001). There was significant correlation between the Proteintech hENT1 antibody expression and Ki67 expression (p = 0.02). Knockdown of hENT1 with silencing RNA transfected HepG2 cells was confirmed by Western blot in a time-dependent fashion over 72 hours. The antibodies (Mackey; Proteintech; Ki67) did not achieve significance for predicting OS (p = 0.75; 0.63; 0.22 respectively). Nodal stage (p = 0.03) and grade of tumour differentiation (p = 0.02) were the univariate tumour variables with prognostic utility. Conclusions While the Proteintech antibody demonstrates concordance with the 10D7G2 antibody in determining hENT1 expression the antibodies did not demonstrate significant prognostic ability in this proof-of-concept study. Standard histopathological co-variates retain prognostic utility within the cohort.

O-L02 Evaluation of the Utility of Prognostic Models for Patients Diagnosed with Peri-hilar Cholangiocarcinoma

Background Several potential prognostic models have been developed to stratify patients with peri-hilar cholangiocarcinoma (PHC) by Overall Survival (OS). The American Joint Committee on Cancer (AJCC) staging system is a post-resectional model utilising tumour-specific pathological parameters to stratify and predict OS. The Mayo Clinical (MC) scoring system has been developed utilising primarily clinical, serological, and radiological variables to predict survival in all patients with a diagnosis of peri-hilar cholangiocarcinoma. The objective of this study was to evaluate the utility of these models in determining prognosis for all patients presenting to a tertiary treatment centre with PHC. Methods Three hundred and two patients diagnosed with PHC referred to a regional tertiary referral centre between 2008 and 2019 had their demographic and survival data retrospectively analysed from a prospectively held database linked to Hospital Episode Statistics and Somerset Cancer Registry data. One hundred and twenty seven patients were surgically explored. Eight-four patients underwent resection. One-hundred and seventy-four (57.6%) patients underwent palliative endoscopic therapy. Univariate and multivariate modelling was utilised to determine significant prognostic variables. Concordance Indices (C-Indices) were constructed for the prognostic models to determine internal validity within the cohort. Results Multivariate analysis demonstrated that: pre-interventional ECOG status (p < 0.001); serum albumin (p < 0.001); bilirubin levels (p < 0.001); CA 19-9 levels (p < 0.001) and resectional status (p < 0.001) were significant predictors of OS. Patients stratified by the MC scoring system to early-stage disease had a significantly longer OS compared to patients fulfilling late-stage criteria (p < 0.001). The predictive C-Indices for the MC model obtained significance in discriminating OS for the entire cohort (p < 0.05) and un-resected patients (p < 0.05). Neither model attained significant concordance for accurately discriminating OS in post-resectional patients. Conclusions The predictive performance of the stated prognostic models for OS have poor utility. Simple pre-interventional serological, functional and radiological variables appear to provide better prognostic indication of OS. Variables not incorporated in the AJCC registry have a significant effect upon post-resectional OS and require full incorporation in to model prognostication.

O-L08 Prognostic value of body morphometrics in patients undergoing surgery for hilar cholangiocarcinoma

Background Hilar cholangiocarcinoma is an aggressive cancer with poor prognosis. Complex pre-operative workup is required prior to major surgery that frequently involves an extended hepatectomy with biliary reconstruction and is associated with high levels of post-operative morbidity and mortality. Tools to predict overall and disease-specific outcome are required to better tailor pre-habilitation interventions and selection of patients for surgery. Here we investigate whether body morphometrics are associated with disease-free and overall survival. Methods Consecutive patients undergoing resection of hilar cholangiocarcinoma were identified within a prospectively maintained database in a single institution. The CoreSlicer web-based app was used to calculate body morphometrics at the L3 vertebral level (muscle, visceral and subcutaneous fat areas) from portal-phase CT images. Median cut-offs defined patient groups and height-normalised morphometric values were compared at diagnostic and subsequent pre-operative imaging. Multivariate analysis was used to identify relationships between body morphometrics at time of diagnosis, changes in body morphometrics in the pre-operative period and outcome. Results Body morphometrics were assessed in 88 patients at the time of diagnosis. Of these patients, 53 underwent re-staging enabling an assessment of change in body morphometrics during the pre-operative period. Men displayed significantly higher muscle area, visceral fat and lower subcutaneous fat than women. High visceral fat area at diagnosis was an independent predictor of reduced overall survival (HR 1.81, 95% CI 1.1-3.3, P = 0.03), whilst loss of skeletal muscle area during the pre-operative period was an independent predictor of reduced disease-free survival (HR 2.90, 95% CI 1.0-8.8, P = 0.05). Patients with higher visceral fat at diagnosis also appear at increased risk of post-hepatectomy liver failure (PHLF) and experience significantly higher 30-day mortality than those without elevated visceral fat. Conclusions The presented results identify potential value in assessing body morphometrics as a prognostic tool in patients undergoing surgery for hilar cholangiocarcinoma. External validation of these findings in larger patient cohorts will help to determine whether this can be utilised to guide pre-habilitation interventions and appropriately select patients for surgery.