Citations

Abstract Purpose: Quiescin Sulfhydryl Oxidase 1 (QSOX1) is an enzyme over-expressed by tumor cells. Our group and others have shown that QSOX1 is involved in invasion and metastasis. We previously reported that a small molecule, SBI-183, inhibited the enzymatic activity of QSOX1 and suppressed tumor cell invasion in vitro and metastasis of MDA-MB-231 breast tumor cells in vivo. In our current work we tested SPX-009, an analog of SBI-183 with increased potency, to suppress invasion and metastasis in vitro and in vivo. Methods: Commercially available analogs for SBI-183 were screened in a cell-free fluorescent screening assay for the ability to inhibit QSOX1. Analog compounds that inhibited QSOX1 in a concentration-dependent manner were then tested for the ability to inhibit growth and invasion of triple negative breast cancer (TNBC) cells (MDA-MB-231), sarcomatoid kidney cancer cells (RCJ-41T2) and pancreatic adenocarcinoma cells (MIAPaCa2). MTT assays were used to measure the effect of the compounds on tumor growth. 2D invasion assays and 3D tumor spheroid assays were employed to measure the effect of the analogs on invasion. One potent analog (SPX-009) was evaluated for the ability to suppress tumor growth and metastasis in mice bearing MDA-MB-231-luc breast cancer orthotopic xenografts. Results: Three of 53 analogs inhibited the enzymatic activity of QSOX1 at levels similar to the parent compound. However, one of those compounds, SPX-009, suppressed invasion of breast, kidney and pancreas tumor cells in 2D and 3D invasion assays at >10-fold lower concentrations than the parent compound (SBI-183). In a non-metastatic xenograft of kidney cancer SBI-183 suppressed primary kidney tumor growth by 51%, but in a metastatic xenograft breast cancer model (MDA-MB-231-luc TNBC), SBI-183 reduced lung metastasis by 76% compared to control. Human-mouse xenograft studies are ongoing with the more potent analog (SPX-009) and will also be presented. Conclusions: Chemical inhibitors of QSOX1 have a minor effect on tumor cell viability, but a major effect on tumor cell invasion in vitro and metastasis in vivo. This finding suggests that combining a QSOX1 inhibitor with a cytotoxic agent might provide a means to inhibit metastasis of cells that are resistant to cytotoxic agents. Citation Format: Amber Fifield, Thai H. Ho, Douglas O. Faigel, Sergei Svarovsky, Eduard Sergienko, Thomas C. Chung, Douglas F. Lake. Chemical inhibitors of quiescin sulfhydryl oxidase (QSOX1) suppress tumor invasion and metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5323.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS‐CoV‐2) is the etiologic agent causing the disease Corona Virus Disease 19 (COVID‐19), resulting in a worldwide pandemic. Non‐emergent endoscopy services have been disrupted as incidence and hospitalizations were rising. It is anticipated that the peak incidence may be leveling off in many parts of the world, but there is a concern for resurgence of the virus activity. Thus, it is important for endoscopy units to have plans in place during peak times of the epidemic and when resuming endoscopic services as the pandemic wanes. The global endoscopy community is faced with the challenge of providing care during this time. The WEO‐COVID guidance task force has provided this resource document based on the current evidence and consensus opinion. These World Endoscopy Organization (WEO) recommendations are meant to guide endoscopists worldwide, should be interpreted in light of specific clinical conditions and resource availability and may not apply in all situations. This guidance document does not supersede the need to check for all local regulations and legislations.

Abstract Quiescin sulfhydryl oxidase 1 (QSOX1) is an enzyme overexpressed by many different tumor types. QSOX1 catalyzes the formation of disulfide bonds in proteins. Because short hairpin knockdowns (KD) of QSOX1 have been shown to suppress tumor growth and invasion in vitro and in vivo, we hypothesized that chemical compounds inhibiting QSOX1 enzymatic activity would also suppress tumor growth, invasion, and metastasis. High throughput screening using a QSOX1-based enzymatic assay revealed multiple potential QSOX1 inhibitors. One of the inhibitors, known as “SBI-183,” suppresses tumor cell growth in a Matrigel-based spheroid assay and inhibits invasion in a modified Boyden chamber, but does not affect viability of nonmalignant cells. Oral administration of SBI-183 inhibits tumor growth in 2 independent human xenograft mouse models of renal cell carcinoma. We conclude that SBI-183 warrants further exploration as a useful tool for understanding QSOX1 biology and as a potential novel anticancer agent in tumors that overexpress QSOX1.

Endoscopic ultrasound (EUS)-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens are investigative modalities. To evaluate the safety and efficacy of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens. A systematic review of computerized bibliographic databases was carried out for studies of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens from January 1980 to February 2018. EUS-guided cyst ablation-related outcomes (cyst resolution) and complications. Data were extracted from six studies (N=207 patients) for EUS-guided cyst ablation with alcohol lavage and eight studies (N=347 patients) for EUS-guided cyst ablation with paclitaxel-based regimens. The pooled proportion of patients with complete cyst resolution was 68/207 (32.8%) for EUS-guided cyst ablation with alcohol lavage and 221/347 (63.6%) for EUS-guided cyst ablation with paclitaxel. Postablation adverse events with EUS-guided ablation with alcohol lavage were 44/207 (21.7%), and those with EUS-guided ablation with paclitaxel-based regimens were 52/347 (15%). Limitations of this study are because of the variability in study design and regimens tested, paucity of randomized trials, and differences in pancreatic cyst types receiving treatment. EUS-guided cyst ablation appears to be effective and safe. The effect on pancreatic cancer incidence is unknown; EUS-guided pancreatic cyst ablation modalities require further improvement and validation to determine their role in the treatment of patients with pancreatic cystic lesions.

Abstract Background/aims In an investigator-initiated, prospective study, we evaluated the feasibility of a five-gene sequence point-of-care (POC) testing strategy (Xpert CARBA-R Assay, Cepheid Inc., Sunnyvale, CA, USA), compared to reference laboratory PCR (48 – 72 hours turnaround time, two gene sequences), in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and in a hospital outbreak investigation. Methods After informed consent, patients undergoing ERCP (September 2015 – April 2016, n = 191) at Mayo Clinic and potential hospital contacts (n = 9) of an index carbapenem-resistant organism (CRO)-positive inpatient were included. Two rectal swabs, one each for reference and POC assays were obtained. The Xpert CARBA-R Assay enables qualitative rapid detection of five beta-lactamase gene sequences associated with carbapenem-non-susceptibility in Gram-negative bacteria. Feasibility parameters (specimen processing and assay run time, ease of use) and percent agreement between the tests were calculated using JMP Pro11 (SAS Corp, Cary, NC, USA). Results Mean age was 62 ± 15 years; 108 (54 %) were male. Both tests were successfully performed in all patients. The POC test was rated by endoscopy nurses as easy/very easy to conduct in 193 patients (97 %); median assay run time and median time for specimen collection and processing were 55 minutes (interquartile range IQR: 53 – 55 minutes) and 3 minutes (IQR: 3 – 6 minutes), respectively. In 200/201 (99.5 %) tests, there was agreement between the POC and reference PCR. Conclusions The more comprehensive POC CRO testing of patients in the endoscopy suite is feasible and results are available in < 1 hour. This strategy may enable rapid risk stratification of duodenoscope exposure to CRO and potentially improve operational efficiency and decrease costs.

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.

134 Background: Brain metastasis (BM) is an uncommon site of failure in patients (pts) with esophageal cancer (EC) with reported rates between 1-6%. EC pts are living longer with the wider adoption of trimodality therapy and, as with other malignancies, this may change the patterns of failure. We evaluated the incidence and outcomes of BM in EC at Mayo Clinic in Arizona. Methods: A retrospective review identified pts who developed BM from cancer of the esophagus or gastroesophageal junction. A total of 321 patients treated for stage I-IV EC (adenocarcinoma, n = 273; squamous, n = 46; small cell, n = 2) were identified between 1997 and 2012. Fisher’s exact test was used for comparisons. Actuarial survival was calculated using Kaplan-Meier analysis. Results: BM developed in 13 pts (4%), all of whom had adenocarcinoma. Nine pts initially presented with T3 and/or node-positive disease. Four pts presented with metastatic disease to other sites, but only 1 of this group was diagnosed with BM at initial presentation. The median time from initial diagnosis to BM detection was 12 months (range 0-40). All pts were symptomatic at diagnosis. BM was solitary in 6 pts, multiple in 6 pts, and unknown in 1 pt. The posterior fossa was involved in 9 pts. The brain represented the first site of failure in 9 pts. Treatment included surgical resection (n = 5), stereotactic radiosurgery (n = 4), and whole brain radiotherapy (n = 9). Median overall survival was 24 months from initial diagnosis and 5 months from BM detection. Among pts with adenocarcinoma, 3/119 (2.5%) were diagnosed between 1997-2006 compared to 10/154 (6.5%) between 2007-2012 (P = 0.1). Conclusions: The brain remains an uncommon site of failure among pts with EC. A recent series reported an incidence of BM in 13% of pts, raising the possibility of a changing failure pattern. In our series, BM was detected in only 4% of pts. Our study is suggestive of a trend towards increased incidence of BM in more recent years, although it did not reach statistical significance and could be a consequence of the retrospective nature of the study. Both series found BM limited only to pts with adenocarcinoma, and a possible association has been reported between HER-2 overexpression and BM in EC. Therefore, BM in EC may be an interesting area for future study.

158 Background: Esophageal cancer patients (pts) require multidisciplinary management involving thoracic and general surgeons, medical and radiation oncologists, gastroenterologists and psychiatrists. Pts navigate complex medical discussions and endure challenges to nutrition, body image, swallowing mechanics, energy level and weight, mood, and performance status. Coordination of care is complicated by multiple sites of pt entry, complex scheduling requirements, and incomplete information at multidisciplinary consultation. A nurse navigator to coordinate the patient experience may optimize treatment and improve outcomes, quality of life and patient satisfaction. Methods: The nurse navigator evaluates all pt records prior to initial appointment and coordinates scheduling, records acquisition, testing and specialty appointments. The nurse navigator serves as a liaison with pts throughout the course of care and provides a patient navigation book (PNB) as a central source for patient-directed information and record keeping. Benchmarks compared before and after creation of the nurse navigator position include: (1) time from appointment request to multidisciplinary evaluation and start of treatment; (2) completeness of medical records and data (scans, pathology slides); (3) patient awareness of support services for themselves and caregivers; (4) utilization of the PNB; (5) number and frequency of interim hospitalizations and emergency room visits; (6) patient, caregiver, and physician satisfaction. Results: From January to July 2012, 27 gastroesophageal cancer pts have been followed by the nurse navigator. Most of these patients remain on active treatment, hence benchmark analysis is ongoing. Metrics thus far suggest improvement in time to treatment start and awareness of patient resources, use of the PNB and patient satisfaction. Conclusions: Esophageal cancer pts undergo complex and toxic multimodality therapy with curative intent. A dedicated nurse navigator may improve the patient experience, optimize adherence to guideline based therapy and appropriate timeframes and provide continuity to pts undergoing multidisciplinary treatment.