Citations

Background. Adenoma detection rate (ADR) is a validated quality measure for screening colonoscopy, but there are little data for other indications. The distribution of adenomas is not well described for these indications. Aim. To describe ADR and the adenoma distribution in the proximal and distal colon based on colonoscopy indication. Methods. Outpatient colonoscopies are subdivided by indication. PDR and ADR for the entire colon and for proximal and distal colon. Data were compared using generalized estimating equations to adjust for clustering amongst endoscopists while controlling for patient age and gender. Results. 3436 colonoscopies were reviewed (51.2%: men (n=1759)). Indications are screening 49.2%, surveillance 29.3%, change in bowel habit 8.4%, bleeding 5.8%, colitides 3.0%, pain 2.8%, and miscellaneous 1.5%. Overall ADR was 37% proximal ADR 28%, and distal ADR 17%. PDR and ADR were significantly higher in surveillance than in screening (PDR: 69% versus 51%; ADR: 50% versus 33%; p=0.0001). Adenomas were more often detected in the proximal than in the distal colon, for all indications. Conclusions. Prevalence of polyps and adenomas differs based on colonoscopy indication. Adenoma detection is highest in surveillance and more commonly detected in the proximal colon. For quality assurance, distinct ADR and PDR targets may need to be established for different colonoscopy indications.

AbstractBackground and AimFeedback has been shown to improve performance in colonoscopy including adenoma detection rate (ADR). The frequency at which feedback should be given is unknown. As part of a quality improvement program, we sought to measure the outcome of providing quarterly and monthly feedback on colonoscopy quality measures.MethodsAll screening colonoscopies performed at endoscopy unit at Mayo Clinic Arizona by gastroenterologists between October 2010 and December 2012 were reviewed. Quality indicators, including ADR, were extracted for each individual endoscopist, and feedback was provided. The study period was divided into four distinct groups: pre‐intervention that served as baseline, quarterly feedback, monthly feedback, and post‐intervention. Based on ADR, endoscopists were grouped into “low detectors” (≤ 25%), “average detectors” (26–35%), and “high detectors” (> 35%).ResultsA total of 3420 screening colonoscopies were performed during the study period (555 patients during pre‐intervention, 1209 patients during quarterly feedback, 599 during monthly feedback, and 1057 during the post‐intervention period) by 16 gastroenterologists. The overall ADR for the group improved from 30.5% to 37.7% (P = 0.003). Compared with the pre‐interventional period, all quality indicators measured significantly improved during the monthly feedback and post‐intervention periods but not in the quarterly feedback period.ConclusionsIn our quality improvement program, monthly feedback significantly improved colonoscopy quality measures, including ADR, while quarterly feedback did not. The impact of the intervention was most prominent in the “low detectors” group. Results were durable up to 6 months following the intervention.

This pilot study examined the functional impact of computerized versus compensatory calendar training in cognitive rehabilitation participants with mild cognitive impairment (MCI). Fifty-seven participants with amnestic MCI completed randomly assigned calendar or computer training. A standard care control group was used for comparison. Measures of adherence, memory-based activities of daily living (mADLs), and self-efficacy were completed. The calendar training group demonstrated significant improvement in mADLs compared to controls, while the computer training group did not. Calendar training may be more effective in improving mADLs than computerized intervention. However, this study highlights how behavioral trials with fewer than 30–50 participants per arm are likely underpowered, resulting in seemingly null findings.

Genotype, particularly Ras status, greatly affects prognosis and treatment of liver metastasis in colon cancer patients. This pilot aimed to apply word frequency analysis and a naive Bayes classifier on radiology reports to extract distinguishing imaging descriptors of wild-type colon cancer patients and those with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. In this institutional-review-board-approved study, we compiled a SNaPshot mutation analysis dataset from 457 colon adenocarcinoma patients. From this cohort of patients, we analyzed radiology reports of 299 patients (> 32,000 reports) who either were wild-type (147 patients) or had a KRAS (152 patients) mutation. Our algorithm determined word frequency within the wild-type and mutant radiology reports and used a naive Bayes classifier to determine the probability of a given word belonging to either group. The classifier determined that words with a greater than 50% chance of being in the KRAS mutation group and which had the highest absolute probability difference compared to the wild-type group included: “several”, “innumerable”, “confluent”, and “numerous” (p < 0.01). In contrast, words with a greater than 50% chance of being in the wild type group and with the highest absolute probability difference included: “few”, “discrete”, and “[no] recurrent” (p = 0.03). Words used in radiology reports, which have direct implications on disease course, tumor burden, and therapy, appear with differing frequency in patients with KRAS mutations versus wild-type colon adenocarcinoma. Moreover, likely characteristic imaging traits of mutant tumors make probabilistic word analysis useful in identifying unique characteristics and disease course, with applications ranging from radiology and pathology reports to clinical notes.

Abstract Expression of DLL3 was examined in additional tumor types, as it was found to be highly expressed in tumor-initiating cells (TIC) in small cell lung cancer (SCLC), where a DLL3-targeted antibody drug conjugate (ADC), rovalpituzumab tesirine (Rova-T; SC16LD6.5; Saunders et al. 2015 Sci Transl Med 7:302ra136)) exerted clinically meaningful anti-tumor effects in a phase I trial (Spigel et al. 2016 Lancet Oncology; In Press). DLL3 expression was profiled by qRT-PCR, ELISA and immunohistochemistry in multiple tumor types. Patient-derived xenografts (PDX) from melanoma and ovarian small cell carcinoma were established and used for efficacy studies to determine the ability of Rova-T to impact tumor growth and TIC frequency. DLL3 expression was seen in metastatic melanoma (55%), low grade gliomas (90%), glioblastoma (70%), medullary thyroid cancer (65%), carcinoids (33%), dispersed neuroendocrine tumors in the pancreas (9%), bladder (57%) and prostate (24%), testicular cancer (90%), and lung adenocarcinomas with neuroendocrine features (80%). Unlike SCLC, where DLL3 does not predict clinical outcome on standard therapies, DLL3 expression negatively correlates with overall survival in melanoma and small cell bladder cancer. In mice bearing DLL3 positive melanoma PDX, treatment with a single dose of Rova-T resulted in effective and durable responses (&gt;100 days), which correlated with a significant impact on TIC frequency. Similarly, in mice bearing DLL3-positive ovarian small cell PDX, a single dose of Rova-T resulted in effective and durable responses (&gt;100 days). Our results show that DLL3 is expressed in many neuroendocrine tumors (lung, ovarian, prostate, bladder, etc), metastatic melanoma, medullary thyroid cancer, low-grade gliomas and glioblastoma. Given pre-clinical results showing efficacy of Rova-T in melanoma and ovarian small cell carcinoma, as well as encouraging clinical data with Rova-T in patients with recurrent/refractory SCLC, clinical evaluation of Rova-T in DLL3-positive melanoma, glioblastoma, medullary thyroid cancer and other high-grade neuroendocrine carcinomas is warranted. A “basket” trial enrolling patients with DLL3-positive solid tumors is now recruiting patients (NCT02709889). Citation Format: Laura R. Saunders, Samuel A. Williams, Sheila Bheddah, Kumiko Isse, Sarah Fong, Marybeth A. Pysz, Himisha Beltran, Loredana Puca, Verena Sailer, Juan M. Mosquera, Yu Yin, Jiaoti Huang, Andrew J. Armstrong, Jorge Garcia, Cristina Magi-Galluzzi, Vadim Koshkin, Petros Grivas, Farhad Kosari, John Cheville, Justin C. Moser, Thomas J. Flotte, Thorvardur Halfdanarson, Aaron Mansfield, Konstantinos N. Leventakos, Julian R. Molina, Douglas W. Ball, Barry D. Nelkin, Jill E. Shea, Courtney L. Scaife, Scott J. Dylla. Expression of DLL3 in metastatic melanoma, glioblastoma and high-grade extrapulmonary neuroendocrine carcinomas as potential indications for rovalpituzumab tesirine (Rova-T; SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody drug conjugate (ADC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3093. doi:10.1158/1538-7445.AM2017-3093