Effect of preoperative biliary drainage on cholestasis-associated inflammatory and fibrotic gene signatures in perihilar cholangiocarcinoma.

Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of PBD on hepatic gene expression profiles was therefore studied by microarray analysis. Drainage affects inflammatory and fibrotic gene signatures.

Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.

Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram.

BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.

Surgical accuracy in identifying the elbow rotation axis on fluoroscopic images.

PURPOSE: To assess the accuracy of surgeons in identifying elbow rotation axis (RA) on fluoroscopic images and to measure the interobserver variability. METHODS: Five healthy subjects underwent 3-dimensional computed tomography (CT) analysis of their nondominant elbow. Real-time rotation software enabled surgeons to approximate the elbow RA on CT-reconstructed fluoroscopy, which was repeated twice with different starting positions to increase the number of observations. The surgeons used anatomical landmarks of choice. Analysis of variance (ANOVA) was used to determine structural error differences between surgeons, and intraclass correlation coefficients (ICCs) were used to determine the corresponding interobserver variability. RESULTS: Eight subspecialty-trained trauma surgeons (P.K., N.W.L.S., V.M.d.J., P.J., G.M.K., R.W.P., T.S., B.A.v.D.) participated and attempted to identify the RA on reconstructed fluoroscopy. A total of 15 RA definitions on 5 elbows were recorded per surgeon. The surgeons had a mean rotational error of 5° (range, < 1°-13°) and mean translational error of 1 mm (range, < 1-8 mm), compared with the true elbow RA as measured by the 3-dimensional CT analysis. The ANOVA showed structural differences between surgeons in rotational and translational errors, indicating that some surgeons consistently had more accurately identified the elbow RA than others. The ICC was 0.12 for rotational error and 0.10 for translational error, indicating a large interobserver variability. CONCLUSIONS: We show in this in vivo study that identification of the elbow RA on fluoroscopy is associated with substantial rotational errors and large inconsistencies among surgeons. Implementation of standardized anatomical landmarks is required to improve surgeons' accuracy. These landmarks should preferably take into account both the coronal and the sagittal planes, using the orientation of the capitellum and trochlea as well as the posterior distal humeral cortex. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

A preoperative prediction model for anastomotic leakage after rectal cancer resection based on 13.175 patients.

INTRODUCTION: This study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with the power of a large prospective nation-wide population-based study cohort. MATERIALS AND METHODS: A development cohort was formed by using the DCRA (Dutch ColoRectal Audit), a mandatory population-based repository of all patients who undergo colorectal cancer resection in the Netherlands. Patients aged 18 years or older were included who underwent surgical resection for rectal cancer with primary anastomosis (with or without deviating ileostomy) between 2011 and 2019. Anastomotic leakage was defined as clinically relevant leakage requiring reintervention. Multivariable logistic regression was used to build a prediction model and cross-validation was used to validate the model. RESULTS: A total of 13.175 patients were included for analysis. AL was diagnosed in 1319 patients (10%). A deviating stoma was constructed in 6853 patients (52%). The following variables were identified as significant risk factors and included in the prediction model: gender, age, BMI, ASA classification, neo-adjuvant (chemo)radiotherapy, cT stage, distance of the tumor from anal verge, and deviating ileostomy. The model had a concordance-index of 0.664, which remained 0.658 after cross-validation. In addition, a nomogram was developed. CONCLUSION: The present study generated a discriminative prediction model based on preoperatively available variables. The proposed score can be used for patient counselling and risk-stratification before undergoing rectal resection for cancer.

Accuracy in identifying the elbow rotation axis on simulated fluoroscopic images using a new anatomical landmark.

External fixation of the elbow requires identification of the elbow rotation axis, but the accuracy of traditional landmarks (capitellum and trochlea) on fluoroscopy is limited. The relative distance (RD) of the humerus may be helpful as additional landmark. The first aim of this study was to determine the optimal RD that corresponds to an on-axis lateral image of the elbow. The second aim was to assess whether the use of the optimal RD improves the surgical accuracy to identify the elbow rotation axis on fluoroscopy. CT scans of elbows from five volunteers were used to simulate fluoroscopy; the actual rotation axis was calculated with CT-based flexion-extension analysis. First, three observers measured the optimal RD on simulated fluoroscopy. The RD is defined as the distance between the dorsal part of the humerus and the projection of the posteromedial cortex of the distal humerus, divided by the anteroposterior diameter of the humerus. Second, eight trauma surgeons assessed the elbow rotation axis on simulated fluoroscopy. In a preteaching session, surgeons used traditional landmarks. The surgeons were then instructed how to use the optimal RD as additional landmark in a postteaching session. The deviation from the actual rotation axis was expressed as rotational and translational error (±SD). Measurement of the RD was robust and easily reproducible; the optimal RD was 45%. The surgeons identified the elbow rotation axis with a mean rotational error decreasing from 7.6° ± 3.4° to 6.7° ± 3.3° after teaching how to use the RD. The mean translational error decreased from 4.2 ± 2.0 to 3.7 ± 2.0 mm after teaching. The humeral RD as additional landmark yielded small but relevant improvements. Although fluoroscopy-based external fixator alignment to the elbow remains prone to error, it is recommended to use the RD as additional landmark.

In vitro detection of cholangiocarcinoma cells using a fluorescent protein-expressing oncolytic herpes virus.

Pathological confirmation is desired prior to high-risk surgery for suspected perihilar cholangiocarcinoma (PHC), but preoperative tissue diagnosis is limited by poor sensitivity of available techniques. This study aimed to validate whether a tumor-specific enhanced green fluorescent protein (eGFP)-expressing oncolytic virus could be used for cholangiocarcinoma (CC) cell detection. Extrahepatic CC cell lines SK-ChA-1, EGI-1, TFK-1 and control cells (primary human liver cells) were exposed to the oncolytic herpes simplex type 1 virus NV1066 for up to 24 h in adherent culture. The technique was validated for cells in suspension and cultured cells that had been exposed to crude patient bile. Optimal incubation time of the CC cells with NV1066 at a multiplicity of infection of 0.1 was determined at 6-8 h, yielding 15% eGFP-expressing cells, as measured by flow cytometry. Cells were able to survive 2-h crude bile exposure and remained capable of producing eGFP following NV1066 infection. Detection of malignant cells was possible at the highest dilution tested (10 CC cells among 2 × 105 control cells), though hampered by non-target cell autofluorescence. The technique was not applicable to cells in suspension due to insufficient eGFP production. Accordingly, as yet the technique is not suitable for standardized clinical diagnostics in PHC.