KRAS amplification in metastatic colon cancer is associated with a history of inflammatory bowel disease and may confer resistance to anti-EGFR therapy.

Mutations in RAS occur in 30-50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF, and PIK3CA. Molecular testing was performed on 1286 consecutive mCRC from 1271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS, and HRAS for 15, 5, and 2 cases, respectively (6-21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology, and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggest the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.

Risk of bacterial exposure to the endoscopist's face during endoscopy.

BACKGROUND AND AIMS: Nonuniversal use of facial protection during endoscopy may place endoscopists at risk of exposure to blood and body fluids; however, the frequency of exposure is unknown. METHODS: A prospective 6-month study of 4 gastroenterologists using a face shield during endoscopy was undertaken. The face shield was swabbed in a standardized fashion before and at the end of the session. Controls included pre- and post-swabs of face shields placed on the (1) endoscopy suite wall, (2) remote patient intake bay wall, and (3) after deliberate contamination with a colonoscope immediately after colonoscopy. The swabs were cultured for 48 hours, and growth was reported as no growth or by number of colony-forming units (CFUs). The groups were compared for +CFU rate and CFU number. RESULTS: A total of 1100 procedures were performed in 239 endoscopy sessions. The +CFU rate in the pre-endoscopy groups (2%-4.8%, not significant) was significantly lower than the postendoscopist face shield (45.8%, P < .001) and endoscopy suite wall groups (21.4%, P < .001), respectively. Using a cut-off of >15 CFUs as an indicator of definite exposure, the occurrence rate was 5.6 per 100 half days of endoscopy to the endoscopist's face and 3.4 per 100 half days of endoscopy 6 feet away. CONCLUSIONS: This is the first study to quantify the rate of unrecognized exposure to the endoscopist's face to potentially infectious biologic samples during endoscopy (5.6/100 days of endoscopy). This exposure may result in transmission of infectious diseases. As such, we recommend the use of universal facial protection during GI endoscopy.

An Automated Inpatient Split-dose Bowel Preparation System Improves Colonoscopy Quality and Reduces Repeat Procedures.

BACKGROUND/GOALS: Inpatient colonoscopy preparations are often inadequate, compromising patient safety and procedure quality, while resulting in greater hospital costs. The aims of this study were to: (1) design and implement an electronic inpatient split-dose bowel preparation order set; (2) assess the intervention's impact upon preparation adequacy, repeated colonoscopies, hospital days, and costs. STUDY: We conducted a single center prospective pragmatic quasiexperimental study of hospitalized adults undergoing colonoscopy. The experimental intervention was designed using DMAIC (define, measure, analyze, improve, and control) methodology. Prospective data collected over 12 months were compared with data from a historical preintervention cohort. The primary outcome was bowel preparation quality and secondary outcomes included number of repeated procedures, hospital days, and costs. RESULTS: On the basis of a Delphi method and DMAIC process, we created an electronic inpatient bowel preparation order set inclusive of a split-dose bowel preparation algorithm, automated orders for rescue medications, and nursing bowel preparation checks. The analysis data set included 969 patients, 445 (46%) in the postintervention group. The adequacy of bowel preparation significantly increased following intervention (86% vs. 43%; P<0.01) and proportion of repeated procedures decreased (2.0% vs. 4.6%; P=0.03). Mean hospital days from bowel preparation initiation to discharge decreased from 8.0 to 6.9 days (P=0.02). The intervention resulted in an estimated 1-year cost-savings of $46,076 based on a reduction in excess hospital days associated with repeated and delayed procedures. CONCLUSIONS: Our interdisciplinary initiative targeting inpatient colonoscopy preparations significantly improved quality and reduced repeat procedures, and hospital days. Other institutions should consider utilizing this framework to improve inpatient colonoscopy value.

Predictors of Inadequate Inpatient Colonoscopy Preparation and Its Association with Hospital Length of Stay and Costs.

BACKGROUND/AIMS: Adequate bowel preparation is essential to safe and effective inpatient colonoscopy. Predictors of poor inpatient colonoscopy preparation and the economic impacts of inadequate inpatient preparations are not defined. The aims of this study were to (1) determine risk factors for inadequate inpatient bowel preparations, and (2) examine the association between inadequate inpatient bowel preparation and hospital length of stay (LOS) and costs. METHODS: We performed a retrospective cohort study of adult patients undergoing inpatient colonoscopy preparation over 12 months (1/1/2013-12/31/2013). RESULTS: Of 524 identified patients, 22.3% had an inadequate preparation. A multiple logistic regression model identified the following potential predictors of inadequate bowel preparation: lower income (OR 1.11; 95% CI 1.04, 1.22), opiate or tricyclic antidepressant (TCA) use (OR 1.55; 0.98, 2.46), and afternoon colonoscopy (OR 1.66; 1.07, 2.59); as well as American Society of Anesthesiologists (ASA) class ≥3 (OR 1.15; 1.05, 1.25) and symptoms of nausea/vomiting (OR 1.14; 1.04, 1.25) when a fair preparation was considered inadequate. Inadequate bowel preparation was associated with significantly increased hospital LOS (model relative mean estimate 1.25; 95% CI 1.03, 1.51) and hospital costs (estimate 1.31; 1.03, 1.67) when compared to adequate preparations. CONCLUSIONS: The rate of inadequate inpatient bowel preparations is high and associated with a significant increase in hospital LOS and costs. We identified five potential predictors of inadequate inpatient preparation: lower socioeconomic class, opiate/TCA use, afternoon colonoscopies, ASA class ≥3, and pre-preparation nausea/vomiting; these data should guide future initiatives to improve the quality of inpatient bowel preparations.

Assessing bolus retention in achalasia using high-resolution manometry with impedance: a comparator study with timed barium esophagram.

OBJECTIVES: The aim of this study was to assess whether high-resolution impedance manometry (HRIM) could be used to assess bolus retention similar to the timed barium esophagram (TBE). METHODS: Twenty achalasia patients (10 males, aged 21-79 years) were prospectively evaluated with HRIM and TBE to determine the correlation between barium column height and the impedance bolus height (IBH). The TBE protocol used a 200-ml barium challenge and the HRIM protocol used a 200-ml saline challenge protocol. Both protocols were performed in an upright position and the heights of the barium and impedance columns were measured at 1 and 5 min. Analysis of IBH was performed with a topographic technique and a spatial impedance variation plot. RESULTS: There was no significant difference between the median IBH and barium column at 1 min (IBH: 12.0 cm (interquartile range (IQR), 8.0-18.0); TBE: 12.0 cm (IQR, 7.0-19.0); P=0.90) or at 5 min (IBH: 11.0 cm (IQR, 1.0-17.0); TBE: 9.0 cm (IQR, 4.0-12.0); P=0.47). In addition, the correlation between the two measurements at 1 and 5 min was 0.60 and 0.86, respectively. Using a barium column or impedance height of >5.0 as a definition of bolus retention was associated with 75% concordance at 1 min and 95% concordance at 5 min. CONCLUSIONS: There was excellent agreement between TBE and high-resolution impedance manometry (HRIM) for assessing bolus retention at 5 min. Thus, HRM with impedance may be used as a single test to assess bolus retention and motor function in the management of achalasia.

Effect of meal content on heart rate variability and cardiovascular reactivity to mental stress.

Little is known about transient effects of foods and nutrients on reactivity to mental stress. In a randomized crossover study of healthy adults (n=20), we measured heart rate variability (respiratory sinus arrhythmia), blood pressure, and other hemodynamic variables after three test meals varying in type and amount of fat. Measurements were collected at rest and during speech and cold pressor tasks. There were significant postmeal changes in resting diastolic blood pressure (-4%), cardiac output (+18%), total peripheral resistance (-17%), and interleukin-6 (-27%). Heart rate variability and hemodynamic reactivity to stress was not affected by meal content. We recommend that future studies control for time since last meal and continue to examine effects of meal content on heart rate variability.