bluuebunny/crossref_metadata_2025 huggingface dataset:
175 Clinical Usefulness of SMOC1 as a Diagnostic Marker for Colorectal Serrated Lesions and Colorectal Precancerous Lesions
Authors: Aoki Hironori , Yamamoto Eiichiro , Takasawa Akira , Yamano Hiro-o , Harada Taku , Sugai Tamotsu , Suzuki Hiromu
Published: October 2019

INTRODUCTION:

Colorectal serrated lesions (SLs) include hyperplastic polyp (HP), traditional serrated adenoma (TSA) and sessile serrated adenoma/polyp (SSA/P). SSA/Ps are well known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability (MSI). However, clinical and molecular characteristics of TSAs are not fully understood. We have reported that epigenetic silencing of SMOC1 is associated with development of traditional serrated adenomas (TSAs) and that SMOC1 may play a role in neoplastic pathways in TSAs and conventional adenomas.
1
We aimed to clarify the clinical usefulness of SMOC1 in colorectal tumors.

METHODS:

Expression of SMOC1 was analyzed in a series of 127 colorectal tumors and adjacent normal colonic mucosa by immunohistochemistry (IHC). The staining intensity of SMOC1 was assessed as strong (3), moderate (2), weak (1) or negative (0). The proportions of positively stained tumor cells were assessed as 0 to 10 for each staining intensity. Because neoplasm heterogeneity caused varying degrees of immunoreactivity in respective specimens, we used the sum of each intensity × proportion as an IHC score (e.g., intensity × proportion = (3) × 5 + (2) × 3 + (1) × 1 + (0) × 1 = IHC score 22, scale of 0 to 30).

RESULTS:

Our IHC analysis revealed that SMOC1 is abundantly expressed in normal colon, HPs and SSA/Ps, while it was significantly downregulated in TSAs, high-grade adenomas and CRCs. Among serrated lesions, SMOC1 is expressed in HPs, SSA/Ps and SSA/Ps with CRC, while it was significantly downregulated in TSAs and TSAs with CRC. Notably, in TSAs which consisted of flat and protruding subcomponents, SMOC1 expression levels were lower in the protruding portions than those in the flat portions (P < 0.001).

CONCLUSION:

These results suggest that downregulated expression of SMOC1 could be a hallmark of TSAs and conventional adenomas at high risk of developing CRC.
177 The Presence of Clostridioides difficile Strains in the Gut by Next Generation Shotgun Sequencing: Innocent Bystander or Villain?
Authors: Papoutsis Andreas , Campbell Jordana , Hazan-Steinberg Sabine
Published: October 2019

INTRODUCTION:

Pathogenic Clostridioides difficile (C. difficile) is the most common cause of nosocomial infection in the United States. However, the prevalence of C. difficile colonization in the general population is poorly understood. We sought to determine the presence and nature of various C. difficile strains colonizing a representative sample of 17 asymptomatic adult volunteers, consisting of 10 healthy and 7 stable Crohn's patients.

METHODS:

Next-generation (NGS) shotgun sequencing was performed on fecal samples. Following fecal collection, DNA was extracted from stool samples, before being quantitated and normalized for downstream library fabrication utilizing shotgun methodology. Prepared and indexed libraries were subsequently pooled and sequenced on the Illumina NextSeq 550 System. Sample FASTQ files were analyzed with a computational tool (Kraken) profiling the microbial communities from metagenomic sequencing data with species level resolution. Individual microbiome profiles were then analyzed for the presence of C. difficile and specific categorical strains (Figure 1).

RESULTS:

All 17/17 subjects (100%) were found to possess ≥1 strain of C. difficile (Figure 1). The ATCC 43255 strain was the most common strain (94.1% 16/17), followed by QCD-63q42 (88.2% 15/17), and then M120 and QCD-37x79 strains (both identified in 10/17 [58.8%] individuals).

CONCLUSION:

In our representative sample of 17 adult volunteers, all (100%) were found to possess at least one C. difficile strain in their gut, with many colonized by several strains. While it is recognized that some C. difficile strains are pathogenic, our findings indicate that various non-pathogenic C. difficile species make up an important component of the commensal gut microbiome, and may perhaps play a protective role. Although symptomatic toxigenic CDI is a clear indication for therapy, C. difficile colonization with non-toxigenic strains is not believed to be a direct precursor for CDI. These findings demonstrate our need for awareness that numerous strains of C. difficile exist and the relevance of sequencing (a) prior to hospitalization or antibiotic treatment to help predict those at risk of CDI, and (b) after treatment to identify any loss of potentially protective components of our microbiome.
185 Evaluating Dynamics of Bile Acid Metabolism to Predict Recurrence of Clostridioides difficile Infection
Authors: Allegretti Jessica R. , Mullish Benjamin , Nativ Lotem , Marcus Jenna , Marchesi Julian , McDonald Julie A.K. , Pechlivanis Alexandros , Kennedy Kevin , Gerber Georg , Bry Lynn
Published: October 2019

INTRODUCTION:

Recurrent Clostridioides difficile infection (CDI) is a major public health problem. The ability of commensal gut microbiota to metabolize primary into secondary bile acids plays a role in protection against this infection. Current clinical prediction tools for CDI recurrence do not incorporate biomarkers predictive of protective microbiota functionalities. We investigated metabolomic predictors of C. difficile recurrence.

METHODS:

We conducted a prospective longitudinal study of patients experiencing a first CDI episode. Patients testing positive with either enzyme immunoassay (EIA) toxin or polymerase chain reaction (PCR), and being treated for CDI, were eligible for inclusion. Serial stool samples were collected at diagnosis through week-8 post-completion of anti-CDI therapy if no recurrence, or until the point of recurrence (defined as diarrhea with positive C. difficile EIA toxin stool test). Liquid chromatography-mass spectrometry was performed to profile fecal bile acids. The week 1 post-antibiotic time point was chosen to assess for potential predictors. We derived a univariate logistic regression model predicting recurrence and computed the AUC (c-statistic) on discriminatory ability. The Youden index was calculated as the value that maximizes sensitivity and specificity.

RESULTS:

29 first episode CDI patients were enrolled. 10 patients recurred (34.5%) during 8-weeks of follow-up. Average time to recurrence was 1.9 weeks. Two clinical factors were assessed a-priori for recurrence: use of metronidazole vs vancomycin (OR: 3.56, 95% CI 0.61–20.81, P = 0.15) and diagnosis with EIA vs PCR (OR 8.75, 95% CI 1.53–50.1, P = 0.01). At week 1, significantly more of the secondary bile acids lithocholic acid (LCA) and isolithocholic acid were found in non-recurrers vs recurrers (relative abundance per mg of stool: 20395.0 vs 4542.5, P = 0.037 and 4318.0 vs 1122.7, P = 0.031 respectively) (Table 1). As these are co-linear, we proceeded with LCA alone. With Youden index 17025, sensitivity was 80% and specificity was 57.9%, and the overall AUC resulted in a c-statistic of 0.753 (Figure 1a). However, when clinical risk factors were combined with LCA, sensitivity became 90% and specificity was 79%, with c-statistic of 0.91 (Figure 1b).

CONCLUSION:

The secondary bile acid, LCA, a known inhibitor of C. difficile's vegetative growth, predicted eventual recurrence of CDI with moderate accuracy; however, the model improved significantly with the addition of simple clinical variables.
186 Anaerobic Versus Aerobically Prepared Fecal Microbiota Transplantation Capsules: A Pilot Comparative Cohort Analysis Using a Novel Sequencing Approach
Authors: Mendolia Gina M. , Bi Haixin S. , Kassam Zain , Chu Nathaniel , Smith Mark , Alm Eric , Allegretti Jessica R.
Published: October 2019

INTRODUCTION:

Fecal microbiota transplantation (FMT) capsules have emerged as a therapeutic option for recurrent C.difficile infection (rCDI). Standard FMT capsules are prepared under aerobic conditions; however, anaerobic processing limits oxygen's impact on healthy anaerobic microbes, may enhance microbial community viability, improve engraftment, and may in turn increase efficacy. Thus, we compared the engraftment profiles of FMT capsules prepared by aerobic (AER) versus an anaerobic process (ANA) in rCDI patients. We applied a novel DNA-sequencing method (PMA-seq) to differentiate living and dead microbes.

METHODS:

We conducted a prospective cohort study of rCDI patients (3 or more confirmed episodes within 1 year) eligible for standard of care FMT. Subjects were enrolled sequentially to receive either a single administration of 30 capsules of standard AER or ANA. 3 healthy donors were use and stool donation was split; half prepared under anaerobic and half under aerobic conditions. This technique was used to address donor and stool specific confounding effects. All measures were taken to manage oxygen exposure, otherwise the split stool samples were treated identically. ANA preparations occurred inside an anaerobic chamber. Patients were assessed, and stool samples collected at 72 hours, 10 days, 4 weeks and 8 weeks post-FMT. Gut microbial communities were profiled via shotgun metagenomic and 16S sequencing. Additionally, PMA-seq, a novel species-specific live-dead assay was conducted. Pre and post treatment microbiome engraftment outcomes were analyzed. Assessment for clinical cure was done at week 8 [testing via (GDH/EIA)].

RESULTS:

A total of 10 recurrent CDI patients were enrolled (5 AER and 5 ANA). Relevant characteristics were similar between the AER [mean age: 73 (SD = 15.9), mean recurrence 3.4] and ANA groups [mean age: 67.1 years (SD = 18.7), mean recurrence 3.0]. Overall, gut microbial community outcomes from ANA and AER, including alpha diversity, beta diversity and relative abundances, did not vary substantially by 16S, shotgun metagenomic sequencing or PMA-seq (Figures 1 and 2). Clinical cure at week 8 for AER and ANA was 100% (5/5 in each group). Both formulations were safe and well-tolerated.

CONCLUSION:

To our knowledge, this is the first study to compare aerobically versus anaerobically prepared FMT capsules, including assessment of live and dead specific-microbial profiles. This pilot study suggested there were no significant differences in engraftment profiles in rCDI.
187 Poor Bowel Prep Leads to Low Yield for Inpatient Colonoscopies and Significantly Increases Overall Healthcare Cost: It Is High Time to Reevaluate Bowel Prep Options
Authors: Ramireddy Srinivas , Manisundaram Krish , Patil Prithvi , Badillo Ricardo , Davee Tomas , Thosani Nirav
Published: October 2019

INTRODUCTION:

There have been multiple studies reporting inadequate bowel preparation based on standardized scales like Boston bowel preparation scale (BBPS) for inpatients compared to outpatient colonoscopies. Most of these inpatient procedures might be incomplete or inadequate due to bowel prep and they might be repeated the next day putting additional burden on both the patient and hospital financial system or repeated as outpatient. Aim of this study to evaluate retrospectively the efficacy of bowel prep on inpatient colonoscopy and indirectly assess healthcare delivery cost at our institution.

METHODS:

Prospectively collected data for all inpatient colonoscopies done at our center between January 2018 to August 2018 was retrospectively evaluated. All patient's scheduled for inpatient colonoscopy was given split dose bowel preparation according to standard guidelines. Our database included daily endoscopy and floor nurse documentation regarding completeness of bowel prep, procedure cancellation or rescheduling related to poor bowel prep and colonoscopy procedure detail including Boston Bowel Prep Score for each completed procedure. Adequate bowel preparation is consider composite BBPS 7 or above and BBPS 6 or less was considered inadequate bowel prep.

RESULTS:

A total of 246 (n = 246) patients were scheduled for inpatient colonoscopy from January 2018 to August 2018. Of the total patients about 136 (55.5%) patients were male and 110 (44.5%) patients were female with average age of 60.6 ± 16.15 years (Range 18–91 years). Of the total number of patients (200) who completed their procedures, a total of 114 (57.0%) patients had a total score (BBPS Right + BBPS Transverse + BBPS Left) of 7 and above and the rest 86 (43%) patients had a BBPS score of less than 7. For all these patients, a repeat colonoscopy at short interval (within 6 months–1 year) was recommended. Average cost of additional inpatient hospitalization day at our institution is at least 600$. Indirect cost with loss of overall productivity was estimated to be additional 1000$. This each inpatient colonoscopy with poor bowel prep added at least 1600$ in direct and indirect healthcare cost, not counting indirect cost incurred by patient and family members related to loss of productivity.

CONCLUSION:

While colonoscopy remains valuable diagnostic and therapeutic tool, current bowel prep options for inpatient colonoscopy are not sufficient. Alternative means of bowel prep options needs to evaluated in inpatient setting.
190 Anti-Depressant Use Does Not Predict Development of Microscopic Colitis: A Retrospective Case-Controlled Study
Authors: Shenoy Abhishek , Redd Walker D. , Hunold Thomas , Hays R. Ann
Published: October 2019

INTRODUCTION:

Microscopic Colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, non-bloody, watery diarrhea and is diagnosed with colonoscopy (CSPY). Literature is mixed on the association of Anti-Depressant (AD) use and their association with MC. We investigated the association of AD's with MC among patients with clinically significant diarrhea.

METHODS:

We performed a retrospective case-control study of all patients with clinically significant chronic diarrhea whom underwent CSPY to rule out MC from 1/2012–12/2016 at the University of Virginia Hospital. 127 patients diagnosed with MC were propensity score matched to 127 patients with normal biopsies based on age and gender. Patients were excluded if they were <18 years old, inpatients, or had FMT. The primary outcome was history of AD use. The secondary outcome was use of NSAIDs or PPI's. OR was calculated for the primary outcome and binomial logistic regression modeling was used to control for other medication use. Statistical analysis and propensity score matching were performed in R using the MatchIt Package.

RESULTS:

55/127 patients with MC and 45/127 patients with normal biopsies used AD's (OR 1.4; 95% CI (0.65–3.04). No differences were observed among the case and control groups with respect to age, gender, celiac disease, or PPI use. No statistical difference was seen in the lymphocytic (LC) vs. collagenous colitis (CC) subtypes among MC patients with AD use. More patients with AD use had LC than CC but this difference was not clinically or statistically significant. Logistic regression revealed that only NSAID use was a predictor of the development of MC (P < 0.001). Anti-depressant use was not a predictor of MC development. Neither combination of AD and NSAID (P = 0.7385) nor AD and PPI use (P = 0.6892) together was predictive of development of MC.

CONCLUSION:

In this study, a history of AD did not predict a pathologic diagnosis of MC in an at risk population. It remains unclear if PPI's or AD's are associated with the development of MC suggesting that MC development may be iatrogenic. Despite studies on the gut-brain axis and gut microbiota dysbiosis associated with AD's, our series showed no association between AD use and MC. Further studies may prove beneficial in relating the development of MC with long-term AD use and their influence on the microbiome, Based on our data, the diagnosis of MC does not warrant discontinuing AD's especially since depression itself may lead to worsened clinical stability of MC.
192 The Latest Trend and Disparities in Clostridium difficile Colitis Related Hospitalizations in the United States
Authors: Chkhikvadze Tamta , Gigauri Nino , Gogokhia Lasha , Shi Junxin , Kwak Ye Eun
Published: October 2019

INTRODUCTION:

Enterocolitis due to Clostridium Difficile infection (CDI) has been a leading and drastically rising cause of nosocomial infection worldwide. We aimed to examine the trends, demographics and hospital resource utilization of CDI hospitalizations in the United States using the largest available national administrative database.

METHODS:

We analyzed National Inpatient Sample (NIS) database from 2005 to 2016. We extracted patient discharge data using ICD-9 (008.45) and ICD-10 (A04.7) primary diagnoses codes for enterocolitis due to CDI from 2005 to 2014 and 2016, respectively. Combined ICD-9 and ICD-10 diagnoses codes were used for year 2015 due to coding transition. Trend in hospitalization due to enterocolitis from CDI was the primary outcome. Secondary outcomes included inpatient mortality, mean hospital charges, hospital length of stay (LOS) and demographic disparities. Type of hospitals and discharge places for CDI were also analyzed.

RESULTS:

Total of 257,613 CDI enterocolitis admissions were identified from 2005–2016, which is estimated to 1,255,271 hospitalizations nationally. Increasing trends in CDI admissions were noted from 73,611 in 2005 to 106,245 in 2016 (Figure 1). In-hospital mortality demonstrated decreasing trend from 4% in 2005 to 1.3% in 2016. Female represented majority of CDI admissions throughout the entire examined years (65% female vs. 35% male). There was significant racial disparity in CDI admissions, with 77.3% white, 10.5% black, 8.3% Hispanic, 1.3% Asian/Pacific Islander and 2.6% Native American origin. Admissions to teaching hospitals due to CDI showed increasing trend from 37% in 2005 to 60% in 2016, whereas admissions to non-teaching hospitals decreased from 63% in 2005 to 40% in 2016. Mean charges have increased by 8.4% from $34,887 to $37,832 (Table 1), while mean LOS has decreased by 1.6 days, corresponding to −22% change from 2005 to 2016 (Table 2). Most patients were discharged home (59%), while others were discharged to home health care (16%), long-term care facilities (22%) or short term care facilities (1%).

CONCLUSION:

CDI related admissions and mean hospital charges have been increased nationally from 2005 to 2016, despite the decrease in length of stay and in-hospital mortality. Significant racial disparities in CDI admissions persisted throughout the decade. Further research investigating preventive measures to decrease hospitalization and cost as well as to improve racial disparities and resource utilization for CDI is needed.
193 Decreased Levels of High-Molecular-Weight Adiponectin Is Associated With Colorectal Neoplasia in Japan
Authors: Inoue Nagamu , Bessho Rieko , Yoshida Toshifumi , Kashiwagi Kazuhiro , Hirose Hiroshi , Sugino Yoshinori , Iwao Yasushi
Published: October 2019

INTRODUCTION:

In Japan, the incidence and mortality rate of colorectal cancer (CRC) has been increased and CRC is considered to be one of obesity-related malignancies. Adiponectin is an adipocyte-specific adipokine, which possesses pleiotropic properties on various disease including atherosclerotic diseases, cardiovascular diseases, inflammatory diseases and tumors. In addition, recent studies have demonstrated that high-molecular-weight (HMW) form of adiponectin is active form of this adipokine. The objective of the present study was to investigate whether HMW adiponectin was a risk factor for colorectal neoplasia (CRN; adenomatous polyp ≥5 mm in size and cancer) using comprehensive health checkup data.

METHODS:

We conducted a retrospective analysis in clinical practice at a single center. Among 10138 subjects who took comprehensive health checkup at our hospital between in August 2012 and December 2016, 315 subjects who underwent screening both colonoscopy and optional metabolic syndrome course were enrolled. HMW adiponectin was measured using commercially available ELISA kit. We evaluated demographic characteristics, anthropometric measurements, visceral fat area (VFA) measured by CT, hematological metabolic parameters, degree of liver fat evaluated by ultrasonography, and current smoking and drinking habits as variables. Association between variables and CRN was evaluated by univariate analysis using t-test, χ2 test, Mann-Whitney test, and then by multivariate analysis using multiple logistic regression model. A P value <0.05 was considered statistically significant.

RESULTS:

Of 315 subjects (men: 228, women: 87) analyzed, 97 subjects were diagnosed as MetS (30.8%) and 33 subjects had CRN (10.5%). Subjects with MetS had more CRN (12 subjects, 12.4%) compared with those without MetS (21 subjects, 9.6%) (n.s.). Univariate analysis identified significant association of sex, age, VFA, systolic blood pressure, current smoking habits, drinking habits and ≥10 kg weight gain compared with the body weight at the age of twenty with CRN prevalence. Moreover, HMW adiponectin level was inversely corelated with CRN prevalence (P = 0.003). Logistic regression analysis revealed that age, systolic blood pressure, current smoking, and HMW adiponectin level were independent factors associated with CRN prevalence (Table 1).

CONCLUSION:

The present study demonstrated that decreased levels of HMW adiponectin is a risk factor for colorectal neoplasia in Japan.
195 Adequacy Rates of Magnesium Citrate Bowel Preparation in a Large Retrospective Cohort
Authors: Alsamman Mohd Amer , Leung Stephanie , Moustafa Abdelmoniem , Baird Grayson , Shah Samir A.
Published: October 2019

INTRODUCTION:

Magnesium Citrate (MC) is not FDA approved as a colonoscopy preparation, but has been used widely in Europe. Advantages include low cost and small volume Few studies have evaluated MC as a bowel preparation. A large prospective trial by Gu, where MC (n = 53) had better tolerability and bowel cleansing compared to GoLYTELY but was statistically insignificant likely due to small sample size. Arora found PEG to be superior to MC We evaluated bowel preparations used in an endoscopy center of a Gastroenterology practice. Sample size is the largest for any similar studies (n = 19173).

METHODS:

Electronic Medical Records were queried for colonoscopies between 2010–2016. Bowel prep used, indication for colonoscopy (screening vs other) and preparation adequacy were all documented prospectively but queried for analysis retrospectively. Cases where the prep type was not recorded were excluded. Adequacy was based on numeric grade (0 = excellent, 1 = good, 2 = fair, and 3 = poor), where 0–2 were considered adequate and 3 not. An adequate prep resulted in following guidelines for next interval colonoscopy. Adequacy rates were calculated and compared. Data were analyzed using SAS software.

RESULTS:

A total of 19,173 cases (MC 2 bottles plus 2 Dulcolax (n = 9315), MC 3 bottles (n = 4682), Golytely 4 L (n = 137), Golytely 2 L (n = 72), Miralax (n = 193), Moviprep (n = 153), Nulytely 4 L (n = 145), Halflytely (n = 104), Osmoprep (n = 42), Suprep (n = 208), Combo prep which was a combination of GoLytely or Nulytely with MC (n = 3960), miscellaneous (n = 162)). We divided all into two major groups (Screening colonoscopies and non-screening colonoscopies) and looked at adequacy rate of each preparation used (Table 1). We compared MC 2 bottles and 3 to the rest of the major groups (Table 2).

CONCLUSION:

Our study included a large number of MC (n = 13,997), and we observed an excellent adequacy rate for both 2 bottles and 3 bottles, for both screening and non-screening colonoscopies (all > 90%). This is the largest study evaluating MC as a bowel preparation. Two bottles with Dulcolax were better than 3 bottles, which could be due to better tolerability, combination with Dulcolax or other. We failed to detect a difference between screening and non-screening groups. MC demonstrated better results than GoLYTELY, nonetheless, the sample size for the later was smaller. In conclusion; MC as bowel preparation is an adequate, well tolerated, and inexpensive. In a large retrospective analysis, it compares favorably to other preparations.
198 Incorporating Sacral Nerve Evaluation for Fecal Incontinence Into a Gastroenterology Practice: Initial Experience and Outcomes
Authors: Stone Christian D. , Williams Mary-Jane O.
Published: October 2019

INTRODUCTION:

Fecal incontinence (FI) is a common yet underappreciated condition for which many gastroenterologists (GE) lack training to address in their patients. A potential therapy for FI is sacral nerve evaluation (SNE), a 1-week trial procedure in which electrodes are placed temporarily to stimulate the sacral nerve. A successful SNE trial may then prompt permanent surgical implant of sacral electrodes to provide long term control of FI. Despite encountering many FI patients, GE have been slow to adopt SNE in the management for FI. The goal of this study was to document the experience of introducing the SNE procedure into a GE practice, with a focus on measuring the initial success rate of SNE, and identifying factors that impact patient selection and transition to permanent implant.

METHODS:

SNE was introduced to a single GE practice beginning in October 2017 and the study period ended in April 2019. Patient demographics and clinical data were collected and post-SNE outcomes were assessed. The primary outcome was SNE success defined as ≥ 50% decrease in FI events during the 7-day SNE trial. Factors associated with SNE success were evaluated.

RESULTS:

SNE was performed on 42 patients [31 (76%) female; mean age 62 years (range 27–80)] during the study period with a median follow up time of 49 weeks. In intent-to-treat analysis, SNE success was achieved in 71% (30/42). Of these, 11 (37%) proceeded to permanent implant with 75–100% improvement in FI. Factors associated with SNE success included female gender (OR 2.0), age ≥ 65 (OR 2.4), and absence of complicating diagnoses (OR 4.1; Crohn's, colitis, prior anal surgery). The most common reason for not proceeding to permanent implant was FI improvement from reduction in diarrhea, followed by personal opposition to implant, unrelated new-onset medical condition, and socioeconomic barriers. Only one SNE complication (rash) was reported.

CONCLUSION:

SNE introduced into a GE practice achieved favorable initial success in improving FI and is a safe, viable procedural modality that can ecpand therapeutic options. Older, traditional FI patients were associated with better SNE results. The transition from successful SNE to permanent implant is reduced by multiple disparate factors, some of which could be addressed with more intensive follow up.
202  Colorectal Cancer Incidence and Demographic Trends in Patients Less Than 50 Years Old in a Large Integrated Healthcare System
Authors: Luong Angeline , Fahmy Marianne , Wu Bechien U.
Published: October 2019

INTRODUCTION:

Recent studies show increasing incidence of colorectal cancer (CRC) in adults less than 50 years, though there is limited data about this population. The primary aim of this study was to calculate trends in CRC incidence and average annual percentage change (AAPC) in patients less than 50 years old within a regional integrated health care system. The secondary aim was to determine demographic trends associated with CRC incidence in this younger population.

METHODS:

This is a retrospective cross-sectional study of Kaiser Permanente Southern California (KPSC) members, age 20–49 years from 1996–2016. Unadjusted incidence rates and AAPC were calculated by age (20–29, 30–39, 40–49) and year, and stratified by Surveillance, Epidemiology, and End Results Program (SEER) staging (early stage SEER 0–II; late stage SEER III, IV, VII). Incidence rate ratios (IRR) were calculated based on gender (male, female), age (40–49, 20–39), race/ethnicity (white, Asian, black, Hispanic), and stratified by staging, and location (proximal, distal).

RESULTS:

Among 3,125,389 patients, there were 2,883 (0.09%) age 20–49 years diagnosed with CRC from 1996–2016. Incidence increased up to 2.9% annually; in 20–39 year-olds, late stage colon cancer increased 1.9% annually (95% CI: 0.3, 3.5; P < 0.0001) and late stage rectal cancer increased 3.9% annually (95% CI: 0.6, 7.2; P < 0.0001). Compared to 20–39 year-olds, 40–49 year-olds had up to 5× risk for CRC at any stage and location (IRR 5.86; 95% CI: 4.94, 6.95; P < 0.0001). Men had increased risk for CRC compared to women, with 45% increased risk for proximal tumors (IRR 1.45; 95% CI: 1.24, 1.71; P < 0.0001). Whites and Asians had increased risk for distal tumors, up to 2× risk (IRR 2.0; 95% CI: 1.64, 2.45; P < 0.0001). Both also had higher risk for rectal cancer, up to 2.22× risk (IRR 2.22; 95% CI: 1.84, 2.68; P < 0.0001) compared to Hispanics and up to 56% increased risk (IRR 1.56; 95% CI: 1.24, 1.98; P = 0.0002) compared to blacks. Compared to whites and Asians, blacks had up to 43% increased risk for proximal tumors (IRR 0.57; 95% CI: 0.42, 0.78; P = 0.0003). Hispanics had the lowest risk for CRC at all stages and locations.

CONCLUSION:

The CRC incidence in 20–49 year-olds are increasing, particularly in cases of late stage CRC and among patients between 40–49 years of age. Distribution of tumor location varied by sex as well as race/ethnicity. Further studying of these demographic trends may help inform future screening and prevention strategies.
207 Fecal Microbiota Transplantation With Oral Capsules for Clostridium difficile Infection: Inconsistencies Among Reporting and Impact on Remission Rates
Authors: Chalikonda Divya M. , Kistler Charles , Bhurwal Abhishek
Published: October 2019

INTRODUCTION:

Fecal microbiota transplantation (FMT) has emerged as a safe and effective treatment for recurrent Clostridium difficile infection (rCDI). FMT can be delivered via the upper gastrointestinal tract (UGIT) or lower GIT. Recently, oral capsule delivery has been demonstrated to be non-inferior to other routes. However, oral administration lends the capsule susceptible to pH changes and intestinal microbiota exposures prior to reaching the colon. There is a lack of consistency between studies evaluating FMT capsules with respect to multiple factors. This systematic review aimed at identifying factors within these studies that could impact remission rates such as type of capsule preparation, prior acid suppression therapy and colon preparation before treatment.

METHODS:

An electronic search was conducted using PubMed, Scopus, EMBASE and Cochrane Central Register of Controlled Trials. The search strategy was not limited by language. Search terms for both the free text and medical subject heading (MeSH) included “fecal microbiota transplantation” and “capsule.” Eligibility criteria included clinical trials using FMT for rCDI and delivery by capsule. Exclusion criteria included lack of capsule manufacturing description or endpoints related to CDI resolution.

RESULTS:

The initial search strategy yielded 93 publications. 30 duplicates were removed. 37 were excluded after screening titles and abstracts. 26 full papers were reviewed and of these, 11 met our eligibility criteria (See Table 1). A total of 425 patients were evaluated who underwent FMT via capsule delivery. Remission rates among studies ranged from 68% to 100%. Timeframe defining remission varied among studies, though 10/11 defined remission as resolution of diarrhea at least 8 weeks after FMT. The pooled remission rate was 86.6% in those receiving colon prep prior to FMT, 83.9% in those who received double-encapsulated formulations and 75.4% in those using PPIs prior to FMT (See Table 2). Heterogeneity among reported study protocols prohibited statistical analysis of these factors.

CONCLUSION:

Oral administration of FMT capsules greatly simplifies this treatment option for patients with rCDI. This systematic review highlights inconsistencies in reporting of the methodology used in FMT capsule studies, which can be contributing to variable remission rates. Future randomized trials are needed to compare the various factors outlined above.
208 Neostigmine to Treat Colonic Pseudo-Obstruction in Cancer Patients
Authors: Avila Meera , Ali Sara , Kukreja Keshav , Ahmed Osman , Lee Jeffrey H.
Published: October 2019

INTRODUCTION:

Acute colonic pseudo-obstruction, or Ogilvie's syndrome, usually develops in patients post-operatively or during severe illness. It is defined as massive dilation of the colon without mechanical obstruction. Ogilvie's may resolve with conservative management, but frequently colonic decompression is needed to prevent bowel injury. Neostigmine is a drug used to treat Ogilvie's that can be tried prior to endoscopic decompression. It is a reversible acetylcholinesterase inhibitor, enhancing colonic motor activity. We aim to evaluate the demographics and clinical history of patients with Ogilvie's and the efficacy of neostigmine administration in treating Ogilvie's in our cancer population.

METHODS:

Retrospective data analysis was performed on patients from 2000 to 2018 who had colonic dilation, defined as >8 cm in part of the colon on x-ray or cross-sectional imaging, and received neostigmine.

RESULTS:

The total number of patients in the study was 29. The mean age of patients was 66.7 years old (range: age 46.5–81.0). Of the 29 patients, 5 patients were female (17.2%). Leukemia was the primary malignancy in 10 patients (34.5%) and solid tumor in the other 19 patients (65.5%). Metastatic disease was found in 15 patients (51.7%). Recent chemotherapy was administered to 21 patients (72.4%). The average number of hospitalization days was 34.7 days (range: 2–120 days). Pan-dilation of the colon was noted in 10 patients (34.5%) and cecal dilation alone was noted in 7 patients (24.1%). The mean diameter of dilated colon segment was 10.8 cm (range 8.0–15.0 cm). Post-operative Ogilvie's was noted in 5 patients (17.2%). Active infection was identified in 18 patients (64.2%). One dose of neostigmine was required in 20 patients (71.4%) and remaining patients required 2 or 3 doses. Improvement of Ogilvie's was noted in 23 patients (79.3%) and complete resolution in 13 patients (44.8%). Colonoscopy was needed after a trial of neostigmine in 10 patients (34.5%). Bradycardia due to neostigmine was noted in 3 patients (10.3%) without other complications noted.

CONCLUSION:

In our study evaluating cancer patient, Ogilvie's was more common in elderly male patients with solid tumors and active infection. Metastatic disease was noted in about half of the study patients. It was most common to have pan-colonic dilation and isolated cecal dilation. Administration of neostigmine led to improvement of colonic pseudo-obstruction in the majority of patients (79.3%) with complete resolution noted in 44.8% of patients.
211 Increased Synchronous Neoplasms Among Patients With Small and Diminutive Proximal Hyperplastic Polyps
Authors: Sowa Piotr , Duh Erica , Karnes William
Published: October 2019

INTRODUCTION:

Small right-sided sessile serrated polyps (SSPs) are associated with increased risk of synchronous neoplasia. These lesions are difficult to distinguish from non-precancerous hyperplastic polyps (HPs). Hamoudah et al. published a retrospective cohort study showing that diminutive proximal HPs and SSPs are associated with similar increased rates of synchronous advanced neoplasia among screening colonoscopies. Verification of these findings could impact guidelines that currently consider proximal diminutive HPs as surveillance-irrelevant.

METHODS:

Our data was extracted from UCICQD—a prospective database (est 2012) with polyp location, size, and pathology. Study design was modeled after that of Hamoudah et al, and included screening colonoscopies divided into: Group 1 (G1)—cases with 1–3 proximal HPs ≤10 mm; Group 2 (G2)- cases with no proximal SSPs or HPs; and Group 3 (G3)—cases with 1–2 proximal SSPs ≤10 mm. Synchronous and advanced neoplasms were compared between G1–G3.

RESULTS:

Compared to G2, G1 had higher per case rates of synchronous adenomas (52% vs 43%, P = 0.001), 2 or more SSPs (0.6% vs 0.1%, P = 0.046) and 2 or more adenomas (12.4% vs 8.3%, P = 0.01). Compared to G2, G3 had higher per-case rates of synchronous adenomas (50% vs 43%, P = 0.041), SSPs > 9 mm (3.6% vs 0.1%, P < 0.0001) and advanced neoplasms (16.2% vs 11.9%, P = 0.034) (Table 1). Odds ratios (OR) for G1 relative to G2 was significant for 2 or more adenomas (1.48 [1.06–2.08], P = 0.021). For G3 relative to G2, OR were significant for SSP >9 mm (31.05 [9.50–101.55], P < 0.0001). Considering G1 and G3 together, OR relative to G1 were significant for finding of any adenoma (1.19 [1.02–1.38], P = 0.027), SSP > 9 mm (12.72 [3.91–41.44], <0.0001) and >2 adenomas (1.37 [1.04–1.81]) (Table 2).

CONCLUSION:

Our data confirms Hamoudah et al's findings. Proximal diminutive and small serrated polyps are associated with increased rates and OR for synchronous surveillance relevant and advanced neoplasia. The higher rate of advanced neoplasia among small and diminutive proximal serrated neoplasia was largely accounted for by large SSPs. The surveillance-relevance of proximal small and diminutive serrated lesions is also supported by the increased rate and OR of cases with >2 adenomas. However, studies such as this showing “synchrony” may be insufficient to warrant change in surveillance guidelines, which should be based on “metachrony.”
215  Efficacy and Safety of Upadacitinib as an Induction Therapy for Patients With Moderately-to-Severely Active Ulcerative Colitis: Combined Results From 382 Subjects in the Phase 2b Study U-ACHIEVE
Authors: Higgins Peter , Hébuterne Xavier , Siffledeen Jesse , Zhou Wen , Cataldi Fabio , Xie Wangang , Lacerda Ana , Danese Silvio
Published: October 2019

INTRODUCTION:

We assessed efficacy/safety of upadacitinib (UPA) in a ph 2b induction study (part 1) in pts with moderately-to-severely active ulcerative colitis (UC). Additional Pts were enrolled in part 2. We present the efficacy and safety of the combined results of part 1 and part 2

METHODS:

Adults with moderately-to-severely active UC (Adapted Mayo Score 5–9 points and centrally-read endoscopy subscore 2–3) were randomised 1:1:1:1:1 to receive extended-release UPA7.5, 15, 30, 45 mg once daily (QD) or placebo for 8 wks (N = 250). In part 2, 132 pts were randomised to UPA30 or 45 mg QD with 1:1 allocation for 8 weeks. Pairwise comparisons between UPA and PBO for primary endpoint of clinical remission per Adapted Mayo Score at Week 8 (defined as stool frequency subscore ≤1, rectal bleeding subscore = 0, and endoscopic subscore ≤1) and ranked secondary endpoints were conducted using Cochran-Mantel-Haenszel test stratified by previous biologic use, BL corticosteroid use, and BL Adapted Mayo score. No multiplicity adjustments were applied. Non-responder imputation was used for missing values in 13% of pts. Treatment emergent adverse events (AEs) were reported from first dose of study drug to up to 30 days after last dose.

RESULTS:

A total 382 pts were randomised with mean (SD) age of 42.7 (14.3) yrs and disease duration of 8.4 (7.4) yrs. Primary endpoint of clinical remission, and secondary endpoints of endoscopic improvement, clinical response per Adapted Mayo score, clinical response per Partial Mayo score, endoscopic remission, and histologic improvement were significantly higher with UPA doses ≥30 mg QD vs PBO (Table 1). Incidences of AEs were similar across UPA groups and numerically higher in PBO group. Rates of serious AEs were 10.9%, 0%, 4.1%, 4.3% and 4.9% for PBO and UPA 7.5, 15, 30, and 45 mg QD, respectively. Serious infections occurred in pts receiving PBO (4.3%, n = 2), 15 mg QD (2.0%, n = 1), 30 mg QD (0.9%, n = 1), and 45 mg QD (1.6%, n = 2). One case of herpes zoster and pulmonary embolism (PE)/deep vein thrombosis (DVT) with UPA 45 mg QD were reported. PE/DVT was reported 26 days after study drug discontinuation due to UC worsening and hospitalization. No deaths were reported.

CONCLUSION:

In this combined analysis, primary and ranked secondary endpoints consistently met statistical significance with UPA doses ≥ 30 mg QD vs PBO in pts with moderately-to-severely active UC. These results are consistent with part 1 intention-to-treat analysis.1,2 UPA was well-tolerated and no new safety signals were identified.
218 Regional Variation in Treatment Outcomes in Clostridium difficile Colitis: A Nationwide Analysis
Authors: Berry Davis B. , Abougergi Marwan S.
Published: October 2019

INTRODUCTION:

Treatment outcomes for many medical and surgical conditions have been shown to vary significantly between the different regions of the United States. This study was aimed to determine the regional differences in in-hospital mortality and resource utilization among patients admitted to the hospital with Clostridium Difficile infection (CDI).

METHODS:

This is a retrospective cohort study using the National Inpatient Sample (NIS) 2016. NIS is the largest publicly available all-payer inpatient care database in the United States. Patients were included if they had a principal diagnosis of CDI and were excluded if they were younger than 18 years. The primary outcome was in-hospital mortality. The secondary outcome was resource utilization as measured by hospital length of stay (LOS) and total hospitalization charges. The Northeast, Midwest, South and West regions were compared. Multivariate regression analysis was utilized to account for confounders.

RESULTS:

19,580 patients were included in the study. The mean age was 64 years and 64% of patients were females. Adjusted odds ratios (aOR) and mean differences (aMD) are presented in Table 1. The odds of in-hospital mortality were significantly lower among patients treated in the Midwest compared with the Northeast, West and South (aOR: 0.66, 95% confidence interval (CI): 0.45–0.99, P = 0.04). In addition, patients treated in the Midwest (aMD: −0.74 days, CI: −1 to 0.48 days, P < 0.01) and West (aMD: −0.40 days, CI: −0.67 to 0.12 days, P < 0.01) had significantly shorter mean length of stay compared with those in the Northeast and South. Finally, compared with patients treated in the Northeast, those treated in the Midwest and South had significantly lower mean total hospitalization charges (aMD −$12,693, CI: −$16,075 to −$9,312, P < 0.01 and −$5,647, CI: −$9,074 to −$2,220, P < 0.01, respectively) while those treated in the West had significantly higher mean total hospitalization charges (aMD: $9,796, CI: $5,186–$14,406).

CONCLUSION:

Among patients hospitalized with CDI, in-hospital mortality and resource utilization (LOS and total hospitalization charges) vary significantly across the four United States regions. The lowest mortality rates and resource utilization are in the Midwest. Complex socioeconomic variables likely explain this variation, along with possible variable physician adherence to treatment guidelines. Further research is needed to elucidate this point.
225 Barriers to Endoscopic Mucosal Resection of Large Colorectal Lesions: Results of a Nationwide Survey
Authors: Holmes Ian , Yu Jessica X. , Millar Morgan M. , Malvar Carmel , Nguyen-Vu Tiffany , Gawron Andrew J. , Kwon Richard , Roy Soetikno , Kaltenbach Tonya
Published: October 2019

INTRODUCTION:

Over 90% of complex colon polyps that lack overt features of cancer can be removed using endoscopic mucosal resection (EMR) techniques. EMR is more cost-effective and is associated with less morbidity and mortality than surgery. However, rates of surgical resection have been rising even though extensive evidence suggests endoscopic resection should be first line for the management of complex colon polyps. We aimed to assess perceived barriers towards the utilization of EMR for >2 cm polyps among American endoscopists.

METHODS:

We administered a 21 question web-based survey with Qualtrics software (Provo, UT, USA). The American College of Gastroenterology distributed the survey to their mailing list on January 24, 2019 and closed it on February 21, 2019. We assessed endoscopist and practice characteristics as well as perceived barriers and facilitators of EMR, and compared responses between providers who performed 0–1 EMR per month with 2 or more EMR per month to determine which barriers and facilitators influence the utilization of EMR.

RESULTS:

A total of 8,797 practitioners received the survey, with 415 replies (4.7%). Provider demographics are summarized in Table 1. 275 providers (66.7%) reported performing 2 or more EMRs per month. 146 providers (35.1%) felt their fellowship prepared them poorly for large polyp resection. 237 providers (57.1%) felt that the incorporation of EMR training into fellowship would be very beneficial, followed by higher reimbursement (N = 176, 42.4%) and training on EMR technique (N = 154, 37.1%). Providers who performed 1 or fewer EMR per month were significantly more likely to report that lack of structured training, fear of complications, and uncertainty regarding which lesions were amenable to endoscopic management were barriers to routine use of EMR than providers who performed 2 or more EMR per month (Figure 1). They were also more likely to report improved training to be a facilitator for EMR utilization whereas providers who performed 2 or more EMR per month were more likely to report increased reimbursement as a facilitator for EMR utilization (Figure 2).

CONCLUSION:

We found that endoscopists identified lack of training to be a major barrier to performing EMR, especially for low-volume providers. Increasing reimbursement and training were important potential facilitators identified in our study. Future quality improvement efforts should target these key practice aspects to optimize the endoscopic management of complex colon lesions.
226 Impact of Propofol Sedation on Colonoscopy Quality Metrics: A Population-Based Cohort Study
Authors: Rahman Sheikh H. , Sey Michael , Khanna Nitin , Brahmania Mayur , McDonald Cassandra , Blier Marc-André , Hindi Zaid , Yan Brian , Chakraborty Debarati
Published: October 2019

INTRODUCTION:

The use of propofol during colonoscopy has gained increased popularity due to deeper anesthesia compared to conscious sedation. Whether propofol sedation leads to improved colonoscopy quality metrics is unknown and the aim of our study.

METHODS:

We examined the association between use of propofol sedation and colonoscopy quality metrics, including adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation, and perforation, using colonoscopy quality data prospectively collected by the Southwest Regional Cancer Program, a division of Cancer Care Ontario. All colonoscopies performed for any indication across 21 hospitals in Southwest Ontario between April 2017 and December 2018 were identified. Data collected included patient and endoscopist demographics, procedural indication, bowel preparation quality, type of sedation, cecal intubation, polyp detection, and histology. Multi-variable models were built to assess the relationship between propofol sedation and adenoma detection rate (ADR), polyp detection rate (PRD), cecal intubation, and perforation risk.

RESULTS:

In total, 23,903 colonoscopies were identified, of which 8,533 (35.6%) procedures were performed with propofol sedation. There were no significant differences in ADR (22.6% vs. 21.6%, P = 0.156), PDR (43.9% vs. 42.6%, P = 0.05), or cecal intubation rates (97% vs 96.7%, P 0.192) between the two groups on univariate or multivariate analyses. The event rate for perforation was too low for a meaningful comparison in this analysis (1 propofol vs. 2 events for non-propofol).

CONCLUSION:

In this large colonoscopy cohort, propofol sedation was not associated with improved ADR, PDR, or cecal intubation rates.