Artificial Intelligence-Assisted Cancer Status Detection in Radiology Reports.

Cancer research is dependent on accurate and relevant information of patient's medical journey. Data in radiology reports are of extreme value but lack consistent structure for direct use in analytics. At Memorial Sloan Kettering Cancer Center (MSKCC), the radiology reports are curated using gold-standard approach of using human annotators. However, the manual process of curating large volume of retrospective data slows the pace of cancer research. Manual curation process is sensitive to volume of reports, number of data elements and nature of reports and demand appropriate skillset. In this work, we explore state of the art methods in artificial intelligence (AI) and implement end-to-end pipeline for fast and accurate annotation of radiology reports. Language models (LM) are trained using curated data by approaching curation as multiclass or multilabel classification problem. The classification tasks are to predict multiple imaging scan sites, presence of cancer and cancer status from the reports. The trained natural language processing (NLP) model classifiers achieve high weighted F1 score and accuracy. We propose and demonstrate the use of these models to assist in the manual curation process which results in higher accuracy and F1 score with lesser time and cost, thus improving efforts of cancer research. SIGNIFICANCE: Extraction of structured data in radiology for cancer research with manual process is laborious. Using AI for extraction of data elements is achieved using NLP models' assistance is faster and more accurate.

Longitudinal clinical data improve survival prediction after hematopoietic cell transplantation using machine learning.

ABSTRACT: Serial prognostic evaluation after allogeneic hematopoietic cell transplantation (allo-HCT) might help identify patients at high risk of lethal organ dysfunction. Current prediction algorithms based on models that do not incorporate changes to patients' clinical condition after allo-HCT have limited predictive ability. We developed and validated a robust risk-prediction algorithm to predict short- and long-term survival after allo-HCT in pediatric patients that includes baseline biological variables and changes in the patients' clinical status after allo-HCT. The model was developed using clinical data from children and young adults treated at a single academic quaternary-care referral center. The model was created using a randomly split training data set (70% of the cohort), internally validated (remaining 30% of the cohort) and then externally validated on patient data from another tertiary-care referral center. Repeated clinical measurements performed from 30 days before allo-HCT to 30 days afterwards were extracted from the electronic medical record and incorporated into the model to predict survival at 100 days, 1 year, and 2 years after allo-HCT. Naïve-Bayes machine learning models incorporating longitudinal data were significantly better than models constructed from baseline variables alone at predicting whether patients would be alive or deceased at the given time points. This proof-of-concept study demonstrates that unlike traditional prognostic tools that use fixed variables for risk assessment, incorporating dynamic variability using clinical and laboratory data improves the prediction of mortality in patients undergoing allo-HCT.

Aspirin exposure and its association with metal stent patency in malignant biliary obstruction: a large international multicenter propensity score-matched study.

BACKGROUND AND AIMS: Stent dysfunction is common following endoscopic retrograde cholangiopancreatography (ERCP) with self-expanding metal stent (SEMS) insertion in malignant distal biliary obstruction (MDBO). Chronic aspirin exposure (ASA-E) has been previously shown to potentially decrease this risk. We aim to further ascertain the protective effect of ASA and to identify other predictors of stent dysfunction. METHOD: Multicenter retrospective cohort study (9 Canada and 1 US). MDBO who underwent ERCP-SEMS between 01/2014-12/2019 were included and divided into two cohorts: ASA-E and ASA unexposed (ASA-U). Propensity score-matching (PSM) was performed to limit selection bias. Matched variables included: age, sex, tumor stage, and type of metal stent. The primary outcome was the hazard rate of stent dysfunction. A multivariable Cox proportional hazards model was used to identify independent predictors of stent dysfunction. RESULTS: 1,396 patients were assessed. Following PSM a total of 496 patients were analyzed (248 ASA-E, 248 ASA-U). ERCP-SEMS was associated with high clinical success of 82.2% in ASA-E and 81.2% in ASA-U, p=0.80. A total of 184 patients had stent dysfunction wth a mean stent patency time of 229.9 ± 306.2 days and 245.4 ± 241.4 days in ASA-E and ASA-U, resepectively (p=0.52). On multivariable analysis, ASA-E did not protect against stent dysfunction with a hazard ratio of 1.25 (95% confidence interval, CI: 0.96; 1.63). Pancreatic cancer etiology (HR 1.36, 95% CI:1.15-1.61) predicted stent dysfunction while cancer therapy was protective (HR 0.73, 95% CI: 0.55; 0.96). The use of chronic ASA was not associated with an increased risk for adverse events including bleeding, post-ERCP pancreatitis, and perforation. CONCLUSION: In this large, multicenter study utilizing propensity score-matching, chronic exposure to ASA did not protect against stent dysfunction in MDBO. Instead, the analysis revealed that the etiology of pancreatic cancer was an independent predictor of stent dysfunction while cancer therapy was protective.

Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

Application of Machine Learning to the Prediction of Cancer-Associated Venous Thromboembolism.

Venous thromboembolism (VTE) is a common and impactful complication of cancer. Several clinical prediction rules have been devised to estimate the risk of a thrombotic event in this patient population, however they are associated with limitations. We aimed to develop a predictive model of cancer-associated VTE using machine learning as a means to better integrate all available data, improve prediction accuracy and allow applicability regardless of timing for systemic therapy administration. A retrospective cohort was used to fit and validate the models, consisting of adult patients who had next generation sequencing performed on their solid tumor for the years 2014 to 2019. A deep learning survival model limited to demographic, cancer-specific, laboratory and pharmacological predictors was selected based on results from training data for 23,800 individuals and was evaluated on an internal validation set including 5,951 individuals, yielding a time-dependent concordance index of 0.72 (95% CI = 0.70-0.74) for the first 6 months of observation. Adapted models also performed well overall compared to the Khorana Score (KS) in two external cohorts of individuals starting systemic therapy; in an external validation set of 1,250 patients, the C-index was 0.71 (95% CI = 0.65-0.77) for the deep learning model vs 0.66 (95% CI = 0.59-0.72) for the KS and in a smaller external cohort of 358 patients the C-index was 0.59 (95% CI = 0.50-0.69) for the deep learning model vs 0.56 (95% CI = 0.48-0.64) for the KS. The proportions of patients accurately reclassified by the deep learning model were 25% and 26% respectively. In this large cohort of patients with a broad range of solid malignancies and at different phases of systemic therapy, the use of deep learning resulted in improved accuracy for VTE incidence predictions. Additional studies are needed to further assess the validity of this model.

Learning curves in ERCP during advanced endoscopy training: a Canadian multicenter prospective study.

Background and study aims Growing emphasis on quality and patient safety has supported the shift toward competency-based medical education for advanced endoscopy trainees (AETs). In this study, we aimed to examine Canadian AETs learning curves and achievement of competence using an ERCP assessment tool with strong evidence of validity. Methods This prospective study was conducted at five institutions across Canada from 2017-2018. Data on every fifth procedure performed by trainees were collected using the United Kingdom Joint Advisory Joint Advisory Group of Gastrointestinal Endoscopy (JAG) ERCP Direct Observation of Procedural Skills (DOPS) tool, which includes a four-point rating scale for 27 items. Cumulative sum (CUSUM) analysis was used to create learning curves for overall supervision ratings and ERCP DOPS items by plotting scores for procedures performed during training. Results Eleven trainees who were evaluated for 261 procedures comprised our sample. The median number of evaluations by site was 49 (Interquartile range (IQR) 31-76) and by trainee was 15 (IQR 11-45). The overall cannulation rate by trainees was 82 % (241/261), and the native papilla cannulation rate was 78 % (149/191). All trainees achieved competence in the "overall supervision" domain of the ERCP DOPS by the end of their fellowship. Trainees achieved competency in all individual domains, except for tissue sampling and sphincteroplasty. Conclusions Canadian AETs are graduating from fellowship programs with acceptable levels of competence for overall ERCP performance and for the most specific tasks. Learning curves may help identify areas of deficiency that may require supplementary training, such as tissue sampling.

Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy.

Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or "cancer-killing" viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.

On-chip silicon nano-slab photodetector integrated wavelength division de-multiplexer in the 850 nm band.

We present an on-chip photodetector integrated wavelength filter on a SiN-on-silicon-on-insulator (SOI) platform in the 850 nm wavelength window. The wavelength filter is designed using an echelle grating with a distributed Bragg reflector as the grating reflectors. We present the design and experimental realization of a six-channel wavelength filter with a channel spacing of 10 nm. Experimentally, we achieve an insertion loss of 4.3 dB and an adjacent channel cross talk of 22 dB. We demonstrate a silicon nano-slab waveguide integrated metal-semiconductor-metal photodetector with a maximum responsivity of 0.56 A/W and dark current of 217 nA. Furthermore, we demonstrate the integration of the echelle grating with the detector and show the feasibility of a CMOS compatible SiN-on-SOI platform for various applications, including short-reach communication and sensing applications.

Comprehensive grating enabled silicon nitride fiber-chip couplers in the SNIR wavelength band.

We present silicon nitride grating enabled fiber-chip coupling in the sub-near-infrared band. We present a comprehensive design and simulation and experimental demonstration of uniform and apodized grating couplers, with and without bottom reflectors. The mode engineering yields a best efficiency of -1.6 dB for apodized grating design, which is further improved to -0.66 dB with a bottom reflector. Experimentally, we demonstrate a coupling efficiency of -2.2 dB for the optimized design. Furthermore, we present a detailed simulation and measurement comparison of various grating parameters and the effect of fabrication tolerances on the grating performance.

Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions. METHODS: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost. RESULTS: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively (P = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE (P = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [P < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [P = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE. CONCLUSION: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost.

Preoperative imaging of gastric GISTs underestimates pathologic tumor size: A retrospective, single institution analysis.

BACKGROUND: How well imaging size agrees with pathologic size of gastric gastrointestinal stromal tumors (GISTs) is unknown. GIST risk stratification is based on pathologic size, location, and mitotic rate. To inform decision making, the size discrepancy between imaging and pathology for gastric GISTs was investigated. METHODS: Imaging and pathology reports were reviewed for 113 patients. Bland-Altman analyses and intraclass correlation (ICC) assessed agreement of imaging and pathology. Changes in clinical risk category due to size discrepancy were identified. RESULTS: Computed tomography (CT) (n = 110) and endoscopic ultrasound (EUS) (n = 50) underestimated pathologic size for gastric GISTs by 0.42 cm, 95% confidence interval (CI): (0.11, 0.73), p = 0.008 and 0.54 cm, 95% CI: (0.25, 0.82), p < 0.001, respectively. ICCs were 0.94 and 0.88 for CT and EUS, respectively. For GISTs ≤ 3 cm, size underestimation was 0.24 cm for CT (n = 28), 95% CI: (0.01, 0.47), p = 0.039 and 0.56 cm for EUS (n = 26), 95% CI: (0.27, 0.84), p < 0.0001. ICCs were 0.72 and 0.55 for CT and EUS, respectively. Spearman's correlation was ≥0.84 for all groups. For GISTs ≤ 3 cm, 6/28 (21.4% p = 0.01) on CT and 7/26 (26.9% p = 0.005) on EUS upgraded risk category using pathologic size versus imaging size. No GISTs ≤ 3 cm downgraded risk categories. Size underestimation persisted for GISTs ≤ 2 cm on EUS (0.39 cm, 95% CI: [0.06, 0.72], p = 0.02, post hoc analysis). CONCLUSION: Imaging, particularly EUS, underestimates gastric GIST size. Caution should be exercised using imaging alone to risk-stratify gastric GISTs, and to decide between surveillance versus surgery.

Compact ring resonator enhanced silicon metal-semiconductor-metal photodetector in SiN-on-SOI platform.

We present a compact on-chip resonator enhanced silicon metal-semiconductor-metal (MSM) photodetector in 850 nm wavelength band for communication and lab-on-chip bio-sensing applications. We report the highest responsivity of 0.81 A/W for a 5 µm long device. High responsivity is achieved by integrating the detector in a silicon nitride ring resonator. The resonance offers 100X responsivity improvement over a single-pass photodetector due to cavity enhancement. We also present a detailed study of the high-speed response of the cavity and single-pass detector. We report an electro-optic bandwidth of 7.5 GHz measured using a femtosecond optical excitation. To the best of our knowledge, we report for the first time silicon nitride resonator integrated Si-MSM detector in SiN-SOI platform.

Advanced Endoscopy Trainee Involvement Early in EUS Training May Be Associated with an Increased Risk of Adverse Events.

BACKGROUND: The quality of endoscopic ultrasound (EUS) involving advanced endoscopy trainees (AETs) is not well understood. In this study, we aimed to examine adverse events (AE) risk and diagnostic yield of EUS procedures involving AETs. METHODS: We conducted a retrospective single-centre review from September 2009 to August 2015. Clinical, procedural, cytological, and hospital visit data within 30 days of the EUS procedure was collected. Primary outcomes were occurrence of an AE and a diagnostic specimen on cytopathology. Each AE was classified as "definitely related," "possibly related," or "not related" to the EUS procedure based on a previously defined consensus approach. Advanced endoscopy trainee involvement was established through the operative report. RESULTS: Our study included 1657 EUS procedures, of which 27% (451 of 1657) involved AETs. Endoscopic ultrasound was most commonly performed to evaluate pancreatic pathology (46% of cases). Overall AE incidence was 3.4%; it was 4.9% when an AET was involved and 2.8% when the EUS was performed without an AET (P = 0.04). The risk of an AE when AETs were involved was greatest in the first three months of training (7.9% versus 2.7%, P = 0.04). Multivariate analysis limited to the first three months of training demonstrated AET involvement to be associated with an increased AE risk after adjusting for patient and procedural factors (adjusted OR 3.2; 95% CI, 1.1-8.7; P = 0.03). The overall diagnostic yield was 76%. This was not compromised by AET involvement for any quartile of training. CONCLUSIONS: We observed an increased risk of EUS-related AEs when procedures involved AETs during the first three months of training.

Screening for esophageal adenocarcinoma and precancerous conditions (dysplasia and Barrett's esophagus) in patients with chronic gastroesophageal reflux disease with or without other risk factors: two systematic reviews and one overview of reviews to inform a guideline of the Canadian Task Force on Preventive Health Care (CTFPHC).

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).

ELEMENT TRIAL: study protocol for a randomized controlled trial on endoscopic ultrasound-guided biliary drainage of first intent with a lumen-apposing metal stent vs. endoscopic retrograde cholangio-pancreatography in the management of malignant distal biliary obstruction.

BACKGROUND & AIMS: Endoscopic ultrasound guided-biliary drainage (EUS-BD) is a promising alternative to endoscopic retrograde cholangiopancreatography (ERCP); however, its growth has been limited by a lack of multicenter randomized controlled trials (RCT) and dedicated devices. A dedicated EUS-BD lumen- apposing metal stent (LAMS) has recently been developed with the potential to greatly facilitate the technique and safety of the procedure. We aim to compare a first intent approach with EUS-guided choledochoduodenostomy with a dedicated biliary LAMS vs. standard ERCP in the management of malignant distal biliary obstruction. METHODS: The ELEMENT trial is a multicenter single-blinded RCT involving 130 patients in nine Canadian centers. Patients with unresectable, locally advanced, or borderline resectable malignant distal biliary obstruction meeting the inclusion and exclusion criteria will be randomized to EUS-choledochoduodenostomy using a LAMS or ERCP with traditional metal stent insertion in a 1:1 proportion in blocks of four. Patients with hilar obstruction, resectable cancer, or benign disease are excluded. The primary endpoint is the rate of stent dysfunction needing re-intervention. Secondary outcomes include technical and clinical success, interruptions in chemotherapy, rate of surgical resection, time to stent dysfunction, and adverse events. DISCUSSION: The ELEMENT trial is designed to assess whether EUS-guided choledochoduodenostomy using a dedicated LAMS is superior to conventional ERCP as a first-line endoscopic drainage approach in malignant distal biliary obstruction, which is an important and timely question that has not been addressed using an RCT study design. TRIAL REGISTRATION: Registry name: ClinicalTrials.gov. Registration number: NCT03870386. Date of registration: 03/12/2019.

High-speed waveguide integrated silicon photodetector on a SiN-SOI platform for short reach datacom.

We present a waveguide integrated high-speed Si photodetector integrated with a silicon nitride (SiN) waveguide on an silicon-on-insulator (SOI) platform for short reach data communication in a 850 nm wavelength band. We demonstrate a waveguide couple Si pin photodetector responsivity of 0.44 A/W at 25 V bias. The frequency response of the photodetector is evaluated by the coupling of a femtosecond laser source through an SiN grating coupler of the integrated photodetector. We estimate a 3 dB bandwidth of 14 GHz at 20 V bias which, to the best of our knowledge, is the highest reported bandwidth for a waveguide integrated Si photodetector. We also present detailed optoelectronic DC and AC characterization of the fabricated devices. The demonstrated integrated photodetector could enable an integrated solution for scaling of short reach data communication and connectivity.

Variable Endoscopist performance in proximal and distal adenoma detection during colonoscopy: a retrospective cohort study.

BACKGROUND: Adenoma Detection Rate (ADR) is a validated colonoscopy quality indicator. In addition to overall ADR, Distal and Proximal Adenoma Detection Rates may provide important colonoscopy quality information. The goal of this study is to determine the association between distal and proximal adenoma detection (AD) and to identify factors contributing to overall, distal, and proximal AD. METHODS: This is a retrospective cohort study of patients with a noted family history of CRC or positive fecal occult blood test who underwent a screening colonoscopy at a regional colorectal cancer (CRC) screening center between May 2009 and December 2011. Data regarding patient demographics, procedure details, endoscopist characteristics and polyp histology were captured. The main outcomes measured were overall, distal, and proximal AD. RESULTS: 1907 patients were included. The median age was 60 years and 42% were male. Endoscopist median overall ADR was 25% (30% male, 21% female). Endoscopist distal ADR was only modestly associated with their proximal ADR (Spearman Rank: 0.51 p = 0.11). Highest overall ADR (29 to 45%) was found for endoscopists whose distal and proximal ADRs were above the group median. In multivariate analysis, factors associated with overall, distal, and proximal AD included age, sex, and endoscopist practicing experience. CONCLUSION: Inclusion of distal and proximal ADRs, in addition to overall ADR, in colonoscopy quality assessment provides the more accurate feedback on endoscopist performance.

Increased prevalence of colonic adenomas in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is the most common lethal genetic illness in the Caucasian population. Studies have shown that CF patients are at an elevated risk of developing colon cancer. Colonic adenomas are the precursors of colon cancer. This study aims to determine the prevalence of adenomas in patients with cystic fibrosis. METHODS: All patients were recruited prospectively at The Ottawa Hospital Cystic Fibrosis Clinic from 2010 through 2015. Baseline demographic and cystic fibrosis disease characteristics were collected from the clinic's CF patient database. Upon presentation at the endoscopy unit, and after a brief history and physical exam, a colonoscopy was performed. Polyps were resected if detected and sent to the pathology department for characterization. Findings were compared with a control group (pairing each CF patient with 5 age and sex-matched controls) of near-average risk patients who underwent a colonoscopy at the same center. RESULTS: Of the 33 patients that provided informed consent to participate in the study, 30 patients underwent colonoscopy and 13/30 (43.3%) were found to have colonic adenomas compared to 7 (4.7%) of the 150 control patients. The relative risk ratio for adenoma detection in a CF patient as compared to a matched control patient was 9.29 (95% CI 4.04-21.31), p<0.01. CONCLUSIONS: Colonic adenomas are more prevalent in CF patients compared to the general population. This study suggests the need for additional research to support recently published screening guidelines for CF patients.

Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity.

Tumors are complex ecosystems composed of networks of interacting 'normal' and malignant cells. It is well recognized that cytokine-mediated cross-talk between normal stromal cells, including cancer-associated fibroblasts (CAFs), vascular endothelial cells, immune cells, and cancer cells, influences all aspects of tumor biology. Here we demonstrate that the cross-talk between CAFs and cancer cells leads to enhanced growth of oncolytic virus (OV)-based therapeutics. Transforming growth factor-ß (TGF-ß) produced by tumor cells reprogrammed CAFs, dampened their steady-state level of antiviral transcripts and rendered them sensitive to virus infection. In turn, CAFs produced high levels of fibroblast growth factor 2 (FGF2), initiating a signaling cascade in cancer cells that reduced retinoic acid-inducible gene I (RIG-I) expression and impeded the ability of malignant cells to detect and respond to virus. In xenografts derived from individuals with pancreatic cancer, the expression of FGF2 correlated with the susceptibility of the cancer cells to OV infection, and local application of FGF2 to resistant tumor samples sensitized them to virotherapy both in vitro and in vivo. An OV engineered to express FGF2 was safe in tumor-bearing mice, showed improved therapeutic efficacy compared to parental virus and merits consideration for clinical testing.