Quantification of Serum Metabolites in Early Colorectal Adenomas Using Isobaric Labeling Mass Spectrometry.

A major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. A blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite level changes of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas (p < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that a few metabolites identified here might contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.

Conserved serum protein biomarkers associated with growing early colorectal adenomas.

A major challenge for the reduction of colon cancer is to detect patients carrying high-risk premalignant adenomas with minimally invasive testing. As one step, we have addressed the feasibility of detecting protein signals in the serum of patients carrying an adenoma as small as 6-9 mm in maximum linear dimension. Serum protein biomarkers, discovered in two animal models of early colonic adenomagenesis, were studied in patients using quantitative mass-spectrometric assays. One cohort included patients bearing adenomas known to be growing on the basis of longitudinal computed tomographic colonography. The other cohort, screened by optical colonoscopy, included both patients free of adenomas and patients bearing adenomas whose risk status was judged by histopathology. The markers F5, ITIH4, LRG1, and VTN were each elevated both in this patient study and in the studies of the Pirc rat model. The quantitative study in the Pirc rat model had demonstrated that the elevated level of each of these markers is correlated with the number of colonic adenomas. However, the levels of these markers in patients were not significantly correlated with the total adenoma volume. Postpolypectomy blood samples demonstrated that the elevated levels of these four conserved markers persisted after polypectomy. Two additional serum markers rapidly renormalized after polypectomy: growth-associated CRP levels were enhanced only with high-risk adenomas, while PI16 levels, not associated with growth, were reduced regardless of risk status. We discuss biological hypotheses to account for these observations, and ways for these signals to contribute to the prevention of colon cancer.

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

BACKGROUND: A major roadblock to reducing the mortality of colorectal cancer (CRC) is prompt detection and treatment, and a simple blood test is likely to have higher compliance than all of the current methods. The purpose of this report is to examine the utility of a mass spectrometry-based blood serum protein biomarker test for detection of CRC. MATERIALS AND METHODS: Blood was drawn from individuals (n = 213) before colonoscopy or from patients with nonmetastatic CRC (n = 50) before surgery. Proteins were isolated from the serum of patients using targeted liquid chromatography-tandem mass spectrometry. We designed a machine-learning statistical model to assess these proteins. RESULTS: When considered individually, over 70% of the selected biomarkers showed significance by Mann-Whitney testing for distinguishing cancer-bearing cases from cancer-free cases. Using machine-learning methods, peptides derived from epidermal growth factor receptor and leucine-rich alpha-2-glycoprotein 1 were consistently identified as highly predictive for detecting CRC from cancer-free cases. A five-marker panel consisting of leucine-rich alpha-2-glycoprotein 1, epidermal growth factor receptor, inter-alpha-trypsin inhibitor heavy-chain family member 4, hemopexin, and superoxide dismutase 3 performed the best with 70% specificity at over 89% sensitivity (area under the curve = 0.86) in the validation set. For distinguishing regional from localized cancers, cross-validation within the training set showed that a panel of four proteins consisting of CD44 molecule, GC-vitamin D-binding protein, C-reactive protein, and inter-alpha-trypsin inhibitor heavy-chain family member 3 yielded the highest performance (area under the curve = 0.75). CONCLUSIONS: The minimally invasive blood biomarker panels identified here could serve as screening/detection alternatives for CRC in a human population and potentially useful for staging of existing cancer.

Safety and efficacy of helminth treatment in relapsing-remitting multiple sclerosis: Results of the HINT 2 clinical trial.

BACKGROUND: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. OBJECTIVE: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). METHODS: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. RESULTS: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. CONCLUSION: TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.

Immunosuppression Does Not Affect Antibody Concentrations to Measles, Mumps, and Rubella in Patients with Inflammatory Bowel Disease.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends using the immunization record and not serologic testing to determine immunity against measles and rubella in the general population, due to potential false negatives. However, it is unknown whether the immune response is less durable among patients who are immunosuppressed. AIMS: The primary aim of this study was to evaluate sustained vaccine-induced measles, mumps, and rubella (MMR) antibody concentrations in immunosuppressed patients with inflammatory bowel disease (IBD). METHODS: We performed a cross-sectional study to compare antibody concentrations following the two-dose (MMR) vaccine among 46 patients with IBD and 20 healthy controls (HC). Three IBD groups stratified by the immunosuppressive regimen that preceded study entry for at least 3 months: (1) thiopurine monotherapy, (2) anti-TNF monotherapy, or (3) combination therapy (anti-TNF agent combined with an immunomodulator) were enrolled. RESULTS: All subjects had measurable antibody concentrations to the three vaccine viruses. Age and time since receipt of MMR series were similar in both groups. There were no difference in the antibody concentration of measles (IBD 667 mIU/ml vs HC 744 mIU/ml; p = 0.45), mumps (IBD 339 EU/ml vs HC 402 EU/ml; p = 0.62), or rubella (IBD 25 mIU/ml vs HC 62 mIU/ml; p = 0.11) among the groups. No differences in antibody concentrations were found among the IBD treatment groups. CONCLUSION: Immunosuppressed patients with IBD have sustained antibody concentrations comparable to healthy controls. Thus, gastroenterologist should follow the ACIP recommendations and use the immunization record when available to determine immunity to measles and rubella in patients with IBD. Clinical Trials Registry # NCT02434133.

Lower Sustained Diphtheria and Pertussis Antibody Concentrations in Inflammatory Bowel Disease Patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients. AIMS: The aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster. METHODS: We performed a cross-sectional study evaluating antibody responses to Tdap vaccine among IBD patients compared to HC. Our study consisted of three patient groups: adults with IBD stratified by maintenance medication regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3) combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate)). RESULTS: Ninety IBD patients and 20 HC participated. Pertussis pertactin antibody concentrations were significantly lower in IBD patients (p = 0.021) compared to HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to those on thiopurine monotherapy (p = 0.028). Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001), and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to the thiopurine monotherapy group (p < 0.001). CONCLUSION: IBD patients on anti-TNF agents had lower antibody concentrations to diphtheria and pertussis. These findings suggest a need for different Tdap booster schedules for IBD patients on anti-TNF therapy. Clinical Trials Registry NCT02434133.

Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates.

OBJECTIVE AND DESIGN: The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6-9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness. RESULTS: The mutational landscape of small polyps is varied both within individual polyps and among the group as a whole but no single alteration was correlated with growth behaviour. Polyps carried 0-3 pathogenic mutations with the most frequent being in APC, KRAS/NRAS, BRAF, FBXW7 and TP53. In polyps with two or more pathogenic mutations, allele frequencies were often variable, indicating the presence of multiple populations within a single tumour. Based on computer modelling, detectable mutations occurred at a mean polyp size of 30±35 crypts, well before the tumour is of a clinically detectable size. CONCLUSIONS: These data indicate that small colon polyps can have multiple pathogenic mutations in crucial driver genes that arise early in the existence of a tumour. Understanding the molecular pathway of tumourigenesis and clonal evolution in polyps that are at risk for progressing to invasive cancers will allow us to begin to better predict which polyps are more likely to progress into adenocarcinomas and which patients are at greater risk of developing advanced disease.

Influence of previous night call and sleep deprivation on screening colonoscopy quality.

OBJECTIVES: There are few studies evaluating the influence of sleep deprivation on endoscopic outcomes. To evaluate the effect of a previous night call on the quality of screening colonoscopies performed the following day. METHODS: Average-risk patients undergoing screening colonoscopies were included. Quality metrics were retrospectively compared between two groups of post-call colonoscopies and colonoscopies performed by the same individuals not on call the night before: those performed by gastroenterologists who were only on call the night prior and those performed by gastroenterologists who performed emergent on-call procedures the night prior. RESULTS: Between 1 July 2010 and 31 March 2012, 447 colonoscopies were performed by gastroenterologists who were on call only the night prior, 126 colonoscopies were performed by gastroenterologists who had completed on-call emergent procedures the night prior, and 8,734 control colonoscopies were completed. There was a lower percent of patients who were screened with adenomas detected in procedures performed by endoscopists who had performed emergent on-call procedures the night prior compared with the controls (30 vs. 39%, respectively; P=0.043). The mean withdrawal time for these colonoscopies was significantly longer than that for the control procedures (15.5 vs. 14.0 min; P=0.025). For the colonoscopies performed by endoscopists who were on call only the night prior, there was no significant difference in the percent of patients screened with adenomas detected compared with controls (42 vs. 39%, respectively; P=0.136). CONCLUSIONS: (1) Despite longer withdrawal times, being on call the night prior and performing an emergent procedure lead to a significant 24% decrease in the adenoma detection rates. (2) It is imperative for screening physicians to be aware of the influence of sleep deprivation on procedural outcomes and to consider altering their practice accordingly.

Assessment of volumetric growth rates of small colorectal polyps with CT colonography: a longitudinal study of natural history.

BACKGROUND: The clinical relevance and in-vivo growth rates of small (6-9 mm) colorectal polyps are not well established. We aimed to assess the behaviour of such polyps with CT colonography assessments. METHODS: In this longitudinal study, we enrolled asymptomatic adults undergoing routine colorectal cancer screening with CT colonography at two medical centres in the USA. Experienced investigators (PJP, DHK, JLH) measured volumes and maximum linear sizes of polyps in vivo with CT colonography scans at baseline and surveillance follow-up. We defined progression, stability, and regression on the basis of a 20% volumetric change per year from baseline (20% or more growth classed as progression, 20% growth to -20% reduction classed as stable, and -20% or more reduction classed as regression). We compared findings with histological subgroups confirmed after colonoscopy when indicated. This study is registered with ClinicalTrials.gov, number NCT00204867. FINDINGS: Between April, 2004, and June, 2012, we screened 22,006 asymptomatic adults and included 243 adults (mean age 57·4 years [SD 7·1] and median age 56 years [IQR 52-61]; 106 [37%] women), with 306 small colorectal polyps. The mean surveillance interval was 2·3 years (SD 1·4; range 1-7 years; median 2·0 years [IQR 1·1-2·3]). 68 (22%) of 306 polyps progressed, 153 (50%) were stable, and 85 (28%) regressed, including an apparent resolution in 32 (10%) polyps. We established immediate histology in 131 lesions on colonoscopy after final CT colonography. 21 (91%) of 23 proven advanced adenomas progressed, compared with 31 (37%) of 84 proven non-advanced adenomas, and 15 (8%) of 198 other lesions (p<0·0001). The odds ratio for a growing polyp at CT colonography surveillance to become an advanced adenoma was 15·6 (95% CI 7·6-31·7) compared with 6-9 mm polyps detected and removed at initial CT colonography screening (without surveillance). Mean polyp volume change was a 77% increase per year for 23 proven advanced adenomas and a 16% increase per year for 84 proven non-advanced adenomas, but a 13% decrease per year for all proven non-neoplastic or unresected polyps (p<0·0001). An absolute polyp volume of more than 180 mm(3) at surveillance CT colonography identified proven advanced neoplasia (including one delayed cancer) with a sensitivity of 92% (22 of 24 polyps), specificity of 94% (266 of 282 polyps), positive-predictive value of 58% (22 of 38 polyps), and negative-predictive value of 99% (266 of 268 polyps). Only 16 (6%) of the 6-9 mm polyps exceeded 10 mm at follow-up. INTERPRETATION: Volumetric growth assessment of small colorectal polyps could be a useful biomarker for determination of clinical importance. Advanced adenomas show more rapid growth than non-advanced adenomas, whereas most other small polyps remain stable or regress. Our findings might allow for less invasive surveillance strategies, reserving polypectomy for lesions that show substantial growth. Further research is needed to provide more information regarding the ultimate fate of unresected small polyps without significant growth. FUNDING: US National Institutes of Health, National Cancer Institute.

Outcomes of colon self-expandable metal stents for malignant vs benign indications at a tertiary care center and review of literature.

BACKGROUND: Endoscopic placement of a self-expandable metal stent (SEMS) is a minimally invasive treatment for use in malignant and benign colonic obstruction. However, their widespread use is still limited with a nationwide analysis showing only 5.4% of patients with colon obstruction undergoing stent placement. This underutilization could be due to perceived increase risk of complications with stent placement. AIM: To review long- and short-term clinical success of SEMS use for colonic obstruction at our center. METHODS: We retrospectively reviewed all the patients who underwent colonic SEMS placement over a eighteen year period (August 2004 through August 2022) at our academic center. Demographics including age, gender, indication (malignant and benign), technical success, clinical success, complications (perforation, stent migration), mortality, and outcomes were recorded. RESULTS: Sixty three patients underwent colon SEMS over an 18-year period. Fifty-five cases were for malignant indications, 8 were for benign conditions. The benign strictures included diverticular disease stricturing (n = 4), fistula closure (n = 2), extrinsic fibroid compression (n = 1), and ischemic stricture (n = 1). Forty-three of the malignant cases were due to intrinsic obstruction from primary or recurrent colon cancer; 12 were from extrinsic compression. Fifty-four strictures occurred on the left side, 3 occurred on the right and the rest in transverse colon. The total malignant case (n = 55) procedural success rate was 95% vs 100% for benign cases (P = 1.0, NS). Overall complication rate was significantly higher for benign group: Four complications were observed in the malignant group (stent migration, restenosis) vs 2 of 8 (25%) for benign obstruction (1-perforation, 1-stent migration) (P = 0.02). When stratifying complications of perforation and stent migration there was no significant difference between the two groups (P = 0.14, NS). CONCLUSION: Colon SEMS remains a worthwhile option for colonic obstruction related to malignancy and has a high procedural and clinical success rate. Benign indications for SEMS placement appear to have similar success to malignant. While there appears to be a higher overall complication rate in benign cases, our study is limited by sample size. When evaluating for perforation alone there does not appear to be any significant difference between the two groups. SEMS placement may be a practical option for indications other that malignant obstruction. Interventional endoscopists should be aware and discuss the risk for complications in setting of benign conditions. Indications in these cases should be discussed in a multi-disciplinary fashion with colorectal surgery.

Fiscal analysis of establishment of a double-balloon enteroscopy program and reimbursement.

BACKGROUND & AIMS: As double-balloon enteroscopy (DBE) programs continue to be established, further research is needed to assess their financial impact. We evaluated actual financial outcomes and compared them with estimated return on investment (ROI) projections for DBE. METHODS: We retrospectively compared the predicted and actual financial results for outpatients referred for DBE at an academic tertiary referral center. RESULTS: The ROI analysis was based on a 5-year time frame. The analysis projected a net present value of $64,623 and an internal rate of return of 24.6%. The projected first-year volume was 52 outpatient cases; however, the actual experience was 20 outpatient cases. The predicted percent margin for these outpatient cases was 16.6%; the actual margin was 24.4%. After 37 months, 52 outpatient cases were completed, and the actual percent margin was 4.6%. Payer type had a significant influence on the financial outcomes when projected activity and actual activity were compared. CONCLUSIONS: Institutions interested in establishing a DBE program should be aware of the financial implications of program establishment, which can be evaluated in a return on investment analysis. Payer mix significantly influences DBE reimbursement and collection rates.

Prospective blinded comparison of polyp size on computed tomography colonography and endoscopic colonoscopy.

BACKGROUND & AIMS: The size of polyps found on computed tomography colonography (CTC) has been suggested as the major determinant of patient management. We compared polyp size as seen on CTC with endoscopic visualization, in vivo probe measurement, and ex vivo size before and after fixation. METHODS: Polyps measured on CTC sent for endoscopic removal were evaluated for polyp size in a blinded fashion by endoscopic estimation, in vivo probe measurement, and after removal. RESULTS: Fifty-six polyps were included in the study. There was no significant difference between CTC polyp size, real-time colonoscopy size estimation, or probe measurement. The size of polyp measured immediately ex vivo and after pathology fixation was significantly smaller. Management would be altered in 6 of 56 polyps (10.7%) on the basis of differences between size of the polyp on endoscopy and CTC. CONCLUSIONS: (1) CTC polyp size measurement is not significantly different from colonoscopy in vivo visual estimation and linear probe measurement. (2) Differences in size of polyps as measured on CTC and endoscopy will affect patient management in 10% of cases.

CT portography with gastric variceal volume measurements in the evaluation of endoscopic therapeutic efficacy of tissue adhesive injection into gastric varices: a pilot study.

BACKGROUND: N-butyl-2-cyanoacrylate (NBCA) injection is used for treating gastric varices (GV). Determining the degree of obliteration of GV is not readily evident at endoscopy. AIMS: The aim of this study was to evaluate CT portography with gastric variceal volume calculations to assess endoscopic therapeutic efficacy of NBCA injection. METHODS: The study design is a retrospective series pilot study. The setting is a single, tertiary care academic medical center. Ten patients underwent esophagogastroduodenoscopy (EGD) with NBCA injection of GV and had biphasic CT scans performed before and after injection therapy. Based on portal venous images, 3D reconstruction and semi-automated volume calculations of GV were performed. Pre and post injection GV volume calculations were compared. RESULTS: The mean pre-procedure GV volume was 89.84 cm3. Eight patients had significant improvement in GV volume from pre-treatment versus post-treatment (95.65 cm3 vs. 49.65 cm3, P-value 0.04). Pre-procedure GV volume was not significantly different in patients treated for active hemorrhage versus no hemorrhage (101.66 cm3 vs. 72.11 cm3, P-value 0.33). Two patients had a subsequent GV hemorrhage after NBCA injection. The mean residual GV volume in these patients versus those that did not re-bleed was significantly more (127.77 cm3 vs. 38.00 cm3, P-value 0.005). CONCLUSIONS: CT portography with measurement of GV volume is a potentially useful tool in determining the therapeutic efficacy NBCA injection of GV. Patients with higher residual GV volumes are at increased risk of hemorrhage and may benefit from repeat injection to reach ideal GV volumes.

CT colonography versus colonoscopy for the detection of advanced neoplasia.

BACKGROUND: Advanced neoplasia represents the primary target for colorectal-cancer screening and prevention. We compared the diagnostic yield from parallel computed tomographic colonography (CTC) and optical colonoscopy (OC) screening programs. METHODS: We compared primary CTC screening in 3120 consecutive adults (mean [+/-SD] age, 57.0+/-7.2 years) with primary OC screening in 3163 consecutive adults (mean age, 58.1+/-7.8 years). The main outcome measures included the detection of advanced neoplasia (advanced adenomas and carcinomas) and the total number of harvested polyps. Referral for polypectomy during OC was offered for all CTC-detected polyps of at least 6 mm in size. Patients with one or two small polyps (6 to 9 mm) also were offered the option of CTC surveillance. During primary OC, nearly all detected polyps were removed, regardless of size, according to established practice guidelines. RESULTS: During CTC and OC screening, 123 and 121 advanced neoplasms were found, including 14 and 4 invasive cancers, respectively. The referral rate for OC in the primary CTC screening group was 7.9% (246 of 3120 patients). Advanced neoplasia was confirmed in 100 of the 3120 patients in the CTC group (3.2%) and in 107 of the 3163 patients in the OC group (3.4%), not including 158 patients with 193 unresected CTC-detected polyps of 6 to 9 mm who were undergoing surveillance. The total numbers of polyps removed in the CTC and OC groups were 561 and 2434, respectively. There were seven colonic perforations in the OC group and none in the CTC group. CONCLUSIONS: Primary CTC and OC screening strategies resulted in similar detection rates for advanced neoplasia, although the numbers of polypectomies and complications were considerably smaller in the CTC group. These findings support the use of CTC as a primary screening test before therapeutic OC.

A comparison of optical colonoscopy and CT colonography screening strategies in the detection and recovery of subcentimeter adenomas.

OBJECTIVES: Evidence has shown that computerized tomographic colonography (CTC) and optical colonoscopy (OC) can detect advanced adenomas at an equal rate; however, a comparison of the subcentimeter adenoma detection has not been performed. The objective of this study is to compare CTC and OC screening programs, with a focus on the detection and recovery of subcentimeter adenomas. METHODS: In all, 1,700 screening OC examinations in average-risk patients were compared with 1,307 CTC examinations in similar patients drawn from the same referral pool completed in 2006-2008. The detection rate for adenomas ≤ 5 mm, 6-9 mm, and <10 mm with advanced histology were compared. RESULTS: In the OC group, 23.2% of patients had at least one adenoma removed; in the CTC screening group, 5.9% of patients had at least one adenoma detected and removed, P<0.001. There were significantly more ≤ 5 mm adenomas (detection rate 0.22, 378/1,700) detected by OC than by CTC (detection rate 0.04, 56/1,307), P<0.001. There were significantly more adenomas 6-9 mm (detection rate 0.12, 204/1,700) detected by OC than by CTC (detection rate 0.05, 67/1,307), with 70 patients with polyps of unknown histology in CTC surveillance, P<0.001. The number of advanced lesions <10 mm detected by OC (15/1,700) compared with CTC (4/1,307) were not significantly different, P=0.06. In the OC group, 27.1% of patients had non-adenomatous polyps removed; in the CTC group, 4.1% of patients had non-adenomatous polyps removed, P<0.001. CONCLUSIONS: (i) An OC screening program detects and recovers a significant four and a half fold greater number of non-advanced adenomas compared with a CTC screening program. (ii) The primary difference between screening with OC and CTC is the recovery and management of the subcentimeter adenoma.

Variation in colonoscopic technique and adenoma detection rates at an academic gastroenterology unit.

The purpose of this research is to evaluate the quality of colonoscopy at an academic institution with a focus on factors influencing withdrawal times and adenoma detection rates. Procedural data and pathologic results of 550 consecutive screening colonoscopies in average risks patients (mean [+/-SD] age, 57 +/- 7.6, 44% male) completed by ten academic gastroenterologists were reviewed. Per individual gastroenterologist, the adenoma detection rates ranged widely from 0.09 to 0.82 adenomas per patient with a mean of 0.46 for the group. The mean withdrawal time was 7.0 min for the group and ranged from 3.4 to 9.6 min. There was a significant positive relationship between the number of adenomas detected and the withdrawal time (P = 0.006). Endoscopists with cecal intubation time to withdrawal time ratios of less than 1 detected significantly more adenomas compared to endoscopists with ratios greater than 1 (P = 0.001). (1) Significant variation in academic gastroenterologists' abilities to detect adenomas during screening colonoscopies exists. (2) Colonoscopic withdrawal time and the cecal intubation to withdrawal time ratio are important factors associated with increased adenoma detection rates.

EUS and ERCP complication rates are not increased in elderly patients.

BACKGROUND: Further studies evaluating the safety of advanced endoscopic procedures in elderly patients are needed. AIM: To evaluate the safety of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) in the elderly. METHODS: The study population, consisting of 1,000 patients who underwent ERCP or EUS, was divided into two cohorts. The elderly cohort consisted of patients ≥ 75 years old. The nonelderly cohort consisted of patients <75 years old. The data collected included demographic information, type of procedure completed, procedure medication used, and endoscopic intervention performed. Complications included any event which occurred during the procedure or up to 1 month post procedure. RESULTS: A total of 600 ERCPs and 400 EUS were included. The mean age of the elderly cohort was 80 years (range 75-95 years, n = 184) versus 54 years (range 13-74 years, n = 816) for the nonelderly cohort. The ERCP complication rate was 10.0% in the elderly versus 10.6% (P = 1.0) for the nonelderly. The EUS complication rate was 4.8% in the elderly versus 3.1% in the nonelderly (P = 0.49). The overall complication rates were identical at 7.6% (P = 1.0). Sedation doses were lower for the elderly cohort (P < 0.001). There was a higher rate of procedure bleeding in the elderly cohort (P = 0.016). CONCLUSION: Advanced age is not a contraindication for advanced endoscopic procedures. There is no significant increase in the rate of overall procedure-related complications seen with either ERCP or EUS in elderly patients; however, elderly patients have a higher risk of bleeding. Less procedure-related sedation medication is required for elderly patients.

Immunogenicity of High Dose Influenza Vaccine for Patients with Inflammatory Bowel Disease on Anti-TNF Monotherapy: A Randomized Clinical Trial.

BACKGROUND: Patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor alpha (TNF) agents may have lower immune response to the influenza vaccine. We aimed to evaluate the immunogenicity of the high dose (HD) vs standard dose (SD) influenza vaccine in patients with IBD on anti-TNF monotherapy. METHODS: We performed a randomized clinical trial at a single academic center evaluating the immunogenicity of the HD vs SD influenza vaccine in patients with IBD on anti-TNF monotherapy. Influenza antibody concentration was measured at immunization, at 2 to 4 weeks postimmunization, and at 6 months. RESULTS: Sixty-nine patients with IBD were recruited into the study, 40 on anti-TNF monotherapy, and 19 on vedolizumab, along with 20 healthy controls (HC). Patients with IBD receiving the HD influenza vaccine had significantly higher H3N2 postimmunization antibodies compared with those who received the SD influenza vaccine (160 [interquartile range 80 to 320] vs 80 [interquartile range 40 to 160]; P = 0.003). The H1N1 postimmunization levels were not significantly higher in the HD influenza vaccine (320 [interquartile range 150 to 320] vs 160 [interquartile range 80 to 320]; P = 0.18). Patients with IBD receiving the HD influenza vaccine and those on vedolizumab who received SD had equivalent antibody concentrations to HC (H1N1 P = 0.85; H3N2 P = 0.23; B/Victoria P = 0.20 and H1N1 P = 0.46; H3N2 P = 0.21; B/Victoria P = 1.00, respectively). CONCLUSIONS: Patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher postimmunization antibody levels compared with SD vaccine. Clinicaltrials.gov (#NCT02461758).

A Prospective, Randomized Comparison of Duodenoscope Reprocessing Surveillance Methods.

Duodenoscope use in healthcare facilities has been associated with transmission of multidrug resistant pathogens between patients. To assist healthcare facilities in monitoring the quality of their duodenoscope reprocessing procedures and limit patient risk of infection, the Centers for Disease Control and Prevention (CDC) deployed voluntary interim duodenoscope sampling and culturing surveillance protocols in 2015. Though the interim methods were widely adopted, alternative surveillance protocols were developed and implemented at individual institutions. Here, we compared two sampling methods-the 2015 CDC interim protocol and an alternative protocol developed by the University of Wisconsin Hospitals and Clinics (UWHC). We hypothesized that the UWHC protocol would detect a higher incidence of bacterial contamination from reprocessed duodenoscopes. A total of 248 sampling events were performed at UWHC. The CDC protocol (n = 129 sampling events) required culturing samples collected from each duodenoscope after brushing its terminal end and flushing its lumen with sterile water. The UWHC protocol (n = 119 sampling events) required culturing samples collected from each duodenoscope after swabbing its elevator, immersing its terminal end into broth and flushing its lumen with saline. With the CDC method, 8.53% (n = 11) of the duodenoscopes sampled were positive for bacterial growth with 15 isolates recovered. Using the UWHC method, 15.13% (n = 18) of cultures were positive for bacterial growth with 20 isolates recovered. The relative risk of identifying a contaminated duodenoscope using the CDC interim method, however, was not different than when using the UWHC protocol. Mean processing time (27.35 and 5.11 minutes, p < 0.001) and total cost per sample event ($17.87 and $15.04) were lower using the UWHC method. As the UWHC protocol provides similar detection rates as the CDC protocol, the UWHC method is useful, provided the shorter processing time and lower cost to perform.

Bleeding stomal varices: case series and systematic review of the literature.

BACKGROUND & AIMS: Bleeding stomal varices are a common problem in patients with surgical stomas and portal hypertension, and remain difficult to diagnose and manage. METHODS: We identified all patients at our institution with bleeding stomal varices from 1989 to 2004. We surveyed all patients undergoing ileal pouch-anal anastomosis from 1997 to 2007 for bleeding anastomotic varices. Finally, we performed a systematic review of the literature focusing on diagnosis and treatment of bleeding stomal varices that included 74 English language studies of 234 patients. RESULTS: We identified 8 patients with bleeding stomal varices. Recognition of stomal varices typically was delayed, particularly when failing to examine the ostomy without the appliance. Stomal variceal bleeding was confirmed by Doppler ultrasound or angiographic imaging. Simple local therapy usually stopped bleeding, albeit temporarily. Sclerotherapy was effective, but at the expense of unacceptable stomal damage. Decompressive therapy was required for secondary prophylaxis, including transjugular intravascular transhepatic shunts (2 patients), surgical portosystemic shunts (2 patients), and liver transplantation (1 patient). No patient with an ileal pouch-anal anastomosis developed anastomotic bleeding from varices. CONCLUSIONS: Primary prevention of bleeding stomal varices requires avoidance of creating enterocutaneous stomas in patients with portal hypertension. Careful inspection of the uncovered ostomy is essential for bleeding stomal varices diagnosis. Once identified, conservative measures will stop bleeding temporarily with definitive therapy required, including transjugular intravascular transhepatic shunts, surgical shunts, or liver transplantation.