Sigmoidoscopy Research Articles

S1691 Colitis in a Rheumatologic Patient

INTRODUCTION: Although a known of cause diarrhea, the pyrimidine synthesis inhibitor leflunomide is a rare cause of overt pancolitis that presents a formidable diagnostic challenge. CASE DESCRIPTION/METHODS: A 46-year-old female with a medical history of psoriatic arthritis was admitted with a two-week history of progressive right upper-quadrant pain, frequent non-bloody diarrhea, tenesmus, and non-bloody emesis. Her immunosuppressant therapy included certolizumab for the past five years and leflunomide for the past 17 months. She denied use of other medications. Initial laboratory evaluation was significant for a mild leukocytosis, lipase of 476 U/L (normal: 12–61 U/L) and C-reactive protein of 50.8 mg/L (normal ≤8.0 mg/L). A stool pathogen panel including Clostridioides difficile was negative. RUQ ultrasound revealed cholelithiasis without cholecystitis. Computed-tomography imaging with contrast revealed no evidence of pancreatitis and mild wall thickening with mucosal hyperenhancement, consistent with ileocolitis (Figure A). A subsequent colonoscopy was notable for circumferential, contiguous inflammation throughout the colon but a normal terminal ileum. Sigmoidal inflammation was mild with a decreased vascular pattern, erythema, and mild friability (Figure B). Biopsy of the descending colon (Figure C) demonstrated surface erosion, crypt abscess (arrowhead) and destruction, and increased lamina propria inflammation without the chronic inflammation classically seen in inflammatory bowel disease. Cytomegalovirus immunostaining was negative. Symptoms persisted despite a three-day course of high-dose intravenous steroids. The decision was made to stop leflunomide, the disease-modifying anti-rheumatologic drug, due to select case reports documenting rare leflunomide-induced colitis. Symptoms improved within two weeks of drug cessation, with a reduction of stool frequency to two formed bowel movements daily, resolution of abdominal pain, and improvement of erythema on repeat flexible sigmoidoscopy. DISCUSSION: This case demonstrates the value of a comprehensive medication history and the diagnostic challenge of leflunomide-induced colitis. Patients with rheumatologic diseases are often on medications with adverse gastrointestinal effects, including biologics, steroids, NSAIDs and other immunomodulators. The lack of randomized studies, vague radiologic, endoscopic and histologic findings, as well as the variable onset after medication initiation makes leflunomide-induced colitis a challenging and rare diagnosis.Figure 1.: Abdominal CT with contrast revealing ileocolitis, mild wall thickening, and mucosal hyperenhancement of the entire colon, consistent with colitis.Figure 2.: Colonoscopy of sigmoid colon revealing mild inflammation with erythema, decreased vascular pattern, and mild friability.Figure 3.: Descending colon; biopsies show surface erosion, crypt abscesses and crypt destruction. There is also increased laminar propria inflammation (100x).

S1618 Finding the Needle in the Haystack: PTLD Occurring in the Background of GVHD and Infection

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is an uncommon complication after hematopoietic stem cell transplant and is associated with Epstein-Barr virus infection and more aggressive immunosuppressive regimens. PTLD can coincide with graft versus host disease (GVHD) and mimic other disorders making endoscopic tissue sampling central to diagnosis and treatment. CASE DESCRIPTION/METHODS: A 27-year-old male was admitted for worsening diarrhea after undergoing umbilical cord blood transplant for Blastic plasmacytoid dendritric cell neoplasm 5 months prior. His transplant course was complicated by several hospitalizations for GVHD of the gut. A colonoscopy 4 months earlier was endoscopically normal with biopsies consistent with GVHD (Figure 1). At this time, the patient presented with 10 days of non-bloody diarrhea in the setting of tapering prednisone dose, similar to prior flares of GVHD. He reported mild chronic abdominal pain but was otherwise asymptomatic. Flexible sigmoidoscopy showed deep linear ulcerations from the proximal rectum to the sigmoid colon with edema, friability, and loss of vascular pattern (Figure 2) which were biopsied. GI PCR returned positive for salmonella and C difficile. A few days later he developed massive hematochezia necessitating ICU level care and massive blood transfusion protocol. Repeat colonoscopy showed interval progression of ulcerations with diffuse bleeding. Biopsies from original flexible sigmoidoscopy showed CD20/EBV + immunoblasts with intermixed CD3+ T cells and polytypic plasma cells (Figure 3) and serum EBV viral load was elevated confirming the diagnosis of PTLD. Patient was started on rituximab and achieved negative viremia after 8 weeks though his course was complicated by recurrent hematochezia. DISCUSSION: The gastrointestinal tract is a common site for PTLD. As patients can present with nonspecific symptoms and confounding diagnoses, identification requires a high index of suspicion. Endoscopic diagnosis through biopsy is critical given the associated high mortality. The characteristic lesion of PTLD in the gastrointestinal tract has been described as a raised, rubbery and erythematous lesion with central ulceration. Although this patient did not have the classic endoscopic finding and had several competing GI diagnoses, he had several risk factors for developing PTLD and once diagnosed responded appropriately to therapy.Figure 1.: First colonoscopy after umbilical cord transplant showed normal endoscopic appearance, random colonic biopsies were consistent with GVHD.Figure 2.: Subsequent flexible sigmoidoscopy showed deep linear ulcerations with edematous mucosa, friability, and loss of vascular pattern in the sigmoid colon just four months later.Figure 3.: H&E stain; 40× field: Atypical lymphoid proliferation as exhibited by numerous large, irregular immunoblasts with prominent nucleoli (examples: black arrows).

S2232 Gastrointestinal Histoplasmosis Masquerading as Crohn’s Disease in the Immunocompetent Adult

INTRODUCTION: A misdiagnosis of gastrointestinal histoplasmosis (GIH) as Crohn’s disease can be catastrophic. Endoscopic data for GIH false negative biopsy rates are not well-established in the literature. CASE DESCRIPTION/METHODS: A 38-year-old female from Ecuador presented to the gastroenterology clinic with abdominal pain, weight loss, and chronic diarrhea. She denied pulmonary symptoms, fever or recent travel for several years. Her past medical and surgical history were significant for treated hepatitis C and C-section. Physical exam revealed a diffuse and mildly tender abdomen. Outpatient colonoscopic exam reported multiple ulcers. Biopsies at ulcer margins revealed non-necrotizing granulomas. Special tests were negative for CMV, TB and fungal organisms. HIV and C. difficile were ruled out. Presumed Crohn’s disease was diagnosed. Mesalamine 1 gm QID and Prednisone 60mg taper were started. At follow up, the patient was admitted to the hospital with worsening diarrhea, abdominal pain and fever. CT abdomen/pelvis showed diffuse enterocolitis. Vancomycin and meropenem were initiated and steroids discontinued. She developed hematochezia requiring multiple blood transfusions. A flexible sigmoidoscopy found severe inflammation extending from the rectum to the sigmoid (Figure 1). A total abdominal colectomy with ileostomy for fulminant and refractory disease was performed. GMS staining revealed a vast number of yeast consistent with histoplasmosis (Figure 2). Amphotericin B followed by itraconazole was started with serial antigen monitoring. The patient’s symptoms resolved and she was discharged with an extended itraconazole regimen. DISCUSSION: This case highlights the unique challenges in GIH. The organism may persist within granulomas for years. Reactivation of latent GIH has been described in the literature and would explain our patient’s disease course. Her initial symptoms could be explained by underlying Crohn’s disease or spontaneous progression of histoplasmosis. Perhaps the greatest challenge was the initial interpretation of the negative GMS stain leading to a significant diagnostic dilemma. Histology with GMS staining may help reveal the organism, and is considered a rapid and reliable diagnostic test. However, sensitivity data is not well established. Previous case series have demonstrated a false negative rate of 11% in an AIDS population. The sensitivity data in immunocompetent hosts is not known. Importantly, a misdiagnosis will lead to treatment error and a potential fatal outcome.Figure 1.: Severe colitis and large sigmoid ulcer with proximal stricture.Figure 2.: GMS stain after total colectomy showing ovoid yeast cells consistent with histoplasma organisms.

S2152 Hypovolemic Shock Due to an Anal Dieulafoy Lesion

INTRODUCTION: Dieulafoy lesions (DL) are dilated submucosal vessels that erode the overlying epithelium. They account for 2–3% of all GI bleeds (GIB). They can occur in any location of the gastrointestinal tract (GIT); however, they are mainly found in the stomach. We present a case of hematochezia resulting in hypovolemic shock from an anal Dieulafoy lesion. CASE DESCRIPTION/METHODS: A 71-year-old male with HTN, DM, PVD on ASA and stage 4 lung cancer on chemo-radiation was admitted for painless hematochezia. Rectal exam revealed dark blood with clots. Thereafter, he started actively bleeding with hypovolemic shock requiring massive transfusion protocol. CT angiography revealed a vascular blush in the left anterior wall of the anorectal junction. Flexible sigmoidoscopy showed active bleeding at the dentate line. The lesion was spurting bright red blood consistent with an arterial bleed. The mucosa around the lesion was normal. Hemostasis was achieved after injecting 5 mL of epinephrine. Due to the location of the lesion, no other endoscopic modalities were attempted. On the following day, bleeding recurred. Interventional radiology (IR) was not considered due to severe stenosis of the iliac vessels. The surgical team was consulted and proceeded with suture ligation of the bleeding arterial vessel. He remained stable with no recurrent episodes and was eventually discharged home. Unfortunately, he passed away three months later due to advanced malignancy. DISCUSSION: DLs are rare but well-recognized cause of GIB. They represent 6% of nonvariceal GIB. The incidence is probably underestimated given the diagnostic challenges. Only a few cases in the literature described anal DL. Occasionally, GIB from DL can be life-threatening. Reported mortality rate is 5%. Pathophysiology is not well established but theories include mucosal ischemia, mucosal atrophy, use of NSAIDs and arterial thromboses. Options of intervention include endoscopy (preferred), radiology and surgery. Endoscopic interventions can be subclassified into regional injection, thermal or mechanical. Endoscopic approach improves mortality and the need for surgical intervention. Recurrence occurs in 9–40% of cases. In our patient, due to the location of the lesion, decision was to avoid using thermal and/or mechanical modalities. Ultimately, hemostasis was achieved via surgical ligation of the vessel. In such cases, we recommend a multidisciplinary team approach including GI, surgery and IR to coordinate appropriate management.Figure 1.: Endoscopic Imaging revealing a bleeding Anal Dieulafoy Lesion.Figure 2.: Endoscopic Imaging revealing a bleeding Anal Dieulafoy Lesion.Figure 3.: Endoscopic Imaging revealing an Anal Dieulafoy Lesion after achieving Hemostasis.

Higher Adenoma Detection Rates at Screening Associated With Lower Long-Term Colorectal Cancer Incidence and Mortality

Background & AimsDetection and removal of adenomas reduces colorectal cancer (CRC) risk. The impact of adenoma detection rates (ADRs) on long-term CRC incidence and mortality is unknown. We investigated this using data from the UK Flexible Sigmoidoscopy Screening Trial.MethodsOf 167,882 UK Flexible Sigmoidoscopy Screening Trial participants, 40,085 were in the intervention arm and underwent flexible sigmoidoscopy screening at 13 trial centers. The median follow-up time was 17 years. At each center, 1 endoscopist performed most flexible sigmoidoscopies. Multivariable logistic regression was used to classify centers into high-, intermediate-, and low-detector groups based on their main endoscopist’s ADR. We calculated the incidence and mortality of distal and all-site CRC, and estimated hazard ratios (HRs) with 95% CIs using Cox regression.ResultsFive, 4, and 4 centers, respectively, were classified into the high-detector, intermediate-detector, and low-detector groups. The average ADRs in each respective group were 15%, 12%, and 9%. Distal CRC incidence and mortality were reduced among those screened compared with controls in all groups, and effects of screening varied significantly by detector ranking, with larger reductions in incidence and mortality seen in the high-detector group (incidence: HR, 0.34; 95% CI, 0.27–0.42; mortality: HR, 0.22, 95% CI, 0.13–0.37) than in the low-detector group (incidence: HR, 0.55; 95% CI, 0.44–0.68; mortality: HR, 0.54; 95% CI, 0.34–0.86). Similar results were observed for all-site CRC, with larger effects seen in the high-detector (incidence: HR, 0.58; 95% CI, 0.50–0.67; mortality: HR, 0.52; 95% CI, 0.39–0.69) than in the low-detector group (incidence: HR, 0.72; 95% CI, 0.61–0.85; mortality: HR, 0.68; 95% CI, 0.51–0.92), although the heterogeneity was not statistically significant.ConclusionsHigher ADRs at screening provide greater long-term protection against CRC incidence and mortality. Isrctn.org, number: ISRCTN28352761.

Development and validation of a model to predict survival in colorectal cancer using a gradient-boosted machine

ObjectiveThe success of treatment planning relies critically on our ability to predict the potential benefit of a therapy. In colorectal cancer (CRC), several nomograms are available to predict different outcomes...

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

Colonoscopy and flexible sigmoidoscopy for follow-up of patients with left-sided diverticulitis.

The prevalence of diverticular disease has been increasing in the western world over the last few decades, causing a growing burden on health care systems. This study compared the uses of flexible sigmoidoscopy with colonoscopy as a follow-up investigation for patients diagnosed with acute left-sided diverticulitis and to evaluate the need for using either procedure. A retrospective study of 327 patients diagnosed with acute diverticulitis was carried out. Of this total, 240 patients with left-sided diverticulitis diagnosed via computed tomography were included. These patients were categorised into two equal groups: the first 120 patients underwent colonoscopy and the second 120 patients underwent flexible sigmoidoscopy. All colonoscopes and flexible sigmoidoscopes confirmed the computed tomography diagnosis of sigmoid diverticular disease with no major new findings. All colonoscopes and flexible sigmoidoscopes were reported as having no complications, with nine colonoscopes reported as being difficult compared with only three flexible sigmoidoscopes. All biopsies were reported as no malignancy. Full bowel preparation was required in all colonoscopes, compared with no preparation required for flexible sigmoidoscopes. There is no evidence to support the routine use of endoscopic evaluation after an episode of left-sided diverticulitis diagnosed on computed tomography if no worrying radiological findings have been reported. This study supports similar findings from other studies and therefore we disagree with The Royal College of Surgeons of England (Association of Coloproctology of Great Britain and Ireland recommendations) commissioning guide, which advocates routine surveillance of the colon.

Prospective audit of the safety of endoscopist-directed nurse-administered propofol sedation in an Australian referral hospital.

Endoscopist directed nurse administered propofol sedation (EDNAPS) is widely considered to be safe and efficient, but there are limited data from the Australian health-care setting, and Australian sedation guidelines do not support the practice. Thus, we report data from a prospective audit of EDNAPS over a 6.5-year period in an Australian referral hospital. Consecutive endoscopic procedures performed between January 2013 and June 2019. Sedation protocol was an initial dose of midazolam 1-3mg intravenously (i.v.) and propofol 10-50mg i.v.. Further aliquots of propofol 10-30mg i.v. were given as required. ProvationMD® endoscopic reporting system was used to prospectively record patient demographics, medication and dose, American Society of Anesthesiologist's (ASA) class, and sedation-related complications. During the 78-month period, 28051 eligible procedures were performed; 3093 procedures performed with anesthetic support or without EDNAPS were excluded. In total, 24958 procedures with EDNAPS were analyzed including 7563 gastroscopies, 12941 colonoscopies, 2932 gastroscopy and colonoscopy, 1440 flexible sigmoidoscopies, and 82 combined gastroscopy and flexible sigmoidoscopy. Of these, 9539 were ASA 1 (38.2%), 13680 were ASA 2 (54.8%), 1733 were ASA 3 (6.9%), and 4 were ASA 4 (0.02%). Sedation-related complications occurred in 66 patients (0.26%), predominantly transient hypoxic episodes. No patient required intubation for an airway emergency, and there was no sedation-related mortality. Sedation-related complications increased with ASA class and were significantly more common with gastroscopy. Endoscopist directed nurse administered propofol sedation is a safe way of performing endoscopic sedation in low-risk patients in the hospital setting.

Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study.

Background Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup who benefited from surveillance and a lower-risk subgroup who may not require surveillance. This study explored whether these findings apply in individuals undergoing CRC screening. Methods This retrospective study used data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention program (KPCP). Screening participants (50 – 74 years) classified as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). Lower- and higher-risk subgroups were defined using our previously identified baseline risk factors: higher-risk participants had incomplete colonoscopies, poor bowel preparation, adenomas ≥ 20 mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence in these subgroups and in the presence vs. absence of surveillance using Cox regression. Results Of 2291 intermediate-risk participants, 45 % were classified as higher risk. Median follow-up was 11.8 years. CRC incidence was higher in the higher-risk than lower-risk subgroup (hazard ratio [HR] 2.08, 95 % confidence interval [CI] 1.07 – 4.06). Surveillance reduced CRC incidence in higher-risk participants (HR 0.35, 95 %CI 0.14 – 0.86) but not statistically significantly so in lower-risk participants (HR 0.41, 95 %CI 0.12 – 1.38). Conclusion As previously demonstrated for hospital patients, screening participants classified as intermediate risk comprised two risk subgroups. Surveillance clearly benefited the higher-risk subgroup.

Gastrointestinal Bleeding in Patients With Coronavirus Disease 2019: A Matched Case-Control Study.

INTRODUCTION:Although current literature has addressed gastrointestinal presentations including nausea, vomiting, diarrhea, abnormal liver chemistries, and hyperlipasemia as possible coronavirus disease 2019 (COVID-19) manifestations, the risk and type of gastrointestinal bleeding (GIB) in this population is not well characterized.METHODS:This is a matched case-control (1:2) study with 41 cases of GIB (31 upper and 10 lower) in patients with COVID-19 and 82 matched controls of patients with COVID-19 without GIB. The primary objective was to characterize bleeding etiologies, and our secondary aim was to discuss outcomes and therapeutic approaches.RESULTS:There was no difference in the presenting symptoms of the cases and controls, and no difference in severity of COVID-19 manifestations (P > 0.05) was observed. Ten (32%) patients with upper GIB underwent esophagogastroduodenoscopy and 5 (50%) patients with lower GIBs underwent flexible sigmoidoscopy or colonoscopy. The most common upper and lower GIB etiologies were gastric or duodenal ulcers (80%) and rectal ulcers related to rectal tubes (60%), respectively. Four of the esophagogastroduodenoscopies resulted in therapeutic interventions, and the 3 patients with rectal ulcers were referred to colorectal surgery for rectal packing. Successful hemostasis was achieved in all 7 cases that required interventions. Transfusion requirements between patients who underwent endoscopic therapy and those who were conservatively managed were not significantly different. Anticoagulation and rectal tube usage trended toward being a risk factor for GIB, although it did not reach statistical significance.DISCUSSION:In COVID-19 patients with GIB, compared with matched controls of COVID-19 patients without GIB, there seemed to be no difference in initial presenting symptoms. Of those with upper and lower GIB, the most common etiology was peptic ulcer disease and rectal ulcers from rectal tubes, respectively. Conservative management seems to be a reasonable initial approach in managing these complex cases, but larger studies are needed to guide management.

Abstract LB-158: Weight change in adulthood and colorectal adenoma incidence in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Obesity is a known risk factor for colorectal cancer, but the influence of weight change during one's lifetime on colorectal adenoma, precursor to colorectal cancer, is less understood. We prospectively investigated the association between weight change in different time periods in adulthood and the risk of colorectal adenoma. We included 1,041 incident distal colorectal adenoma cases (negative on baseline trial flexible sigmoidoscopy screen and positive on follow-up trial sigmoidoscopy screen 3-5 years later) and 16,394 controls (negative on both trial screens) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We required participants to have no history of colorectal polyps, other colon comorbidities or cancer. Using self-reported weight data at trial baseline, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for early-late (age 20-baseline, i.e. ages 55-74), early-middle (age 20-50) and middle-late (age 50-baseline) adulthood weight change with colorectal adenoma using logistic regression. We defined the weight stable group (referent) as weight loss <0.5 kg/5 years or weight gain ≤1 kg/5 years. We defined the weight loss group as those who lost ≥0.5 kg/5 years. We included three weight gain groups: >1 to ≤2, >2 to ≤3 and >3 kg/5 years. We adjusted models for starting BMI (age 20 or 50), age, sex, race, smoking and other factors including diet. Compared to weight stable participants, weight loss in early-late adulthood was inversely associated with colorectal adenoma (OR=0.6, 95% confidence interval (CI): 0.3-0.9); results were similar for early-middle adulthood (OR=0.5, 95% CI: 0.3-0.8), but less pronounced for middle-late adulthood (OR=0.8, 95% CI: 0.7-1.0). Early-late adulthood weight gain of >3 kg/5 years was associated with higher odds of adenoma (OR=1.3, 95% CI: 1.1-1.6); results were similar for middle-late adulthood (OR=1.2, 95% CI: 1.0-1.4), but less pronounced for early-middle adulthood (OR=1.1, 95% CI: 0.9-1.3). We observed some evidence of a stronger association for men than women (for early-late adulthood weight gain >3 kg/5 years, OR for men=1.4, 95% CI: 1.1-1.8; OR for women=1.1, 95% CI: 0.8-1.5), although the interaction was not statistically significant (p-int=0.65). When we stratified by starting BMI, we observed a significantly decreased risk of colorectal adenoma with weight loss from early-late adulthood among those who were overweight/obese at age 20 (OR=0.4, 95% CI: 0.2-0.9). Findings suggest that weight loss in adulthood for those who are overweight/obese is associated with a reduced risk of colorectal adenoma. In addition, our results suggest that a modest rate of weight gain in adulthood of >3 kg/5 years is associated with an increased risk of colorectal adenoma. These findings underscore the importance of healthy weight maintenance in adulthood in preventing colorectal adenoma. Citation Format: Shisi He, Sonja I. Berndt, Andrew T. Kunzmann, Cari M. Kitahara, Wen-Yi Huang, Kathryn Hughes Barry. Weight change in adulthood and colorectal adenoma incidence in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-158.

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of0. Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day98.

Effects of Alternative Offers of Screening Sigmoidoscopy and Colonoscopy on Utilization and Yield of Endoscopic Screening for Colorectal Neoplasms: Protocol of the DARIO Randomized Trial.

BackgroundFlexible sigmoidoscopy and colonoscopy are recommended screening options for colorectal cancer (CRC). Despite colonoscopy being offered for CRC screening in Germany, the uptake of this offer has been very limited.ObjectiveThe objective of this study was to assess the potential for increasing use of endoscopic CRC screening and the detection of advanced colorectal neoplasms by offering the choice between use of flexible sigmoidoscopy and colonoscopy.MethodsThe DARIO study includes a cross-sectional study (part I), followed by a prospective 2-arm randomized controlled intervention trial (part II) with an associated biobank study (part III). Participation is possible in part I of the DARIO study only, parts I and II, or all 3 study parts. After obtaining informed consent from the municipalities, 12,000 people, aged 50-54 years, from the Rhine-Neckar region in Germany were randomly selected from residential lists of the responsible population registries and invited to complete a standardized questionnaire to investigate the nature, frequency, timing, and results of previous CRC screening and eventual diagnostic colonoscopies. In study part II participants from study part I with no colonoscopy in the preceding 5 years are randomized into 2 arms: arm A offering screening colonoscopy only, and arm B offering both options, either screening colonoscopy or screening sigmoidoscopy. The primary endpoint is the proportion of participants in whom colorectal neoplasms >0.5 cm are detected and removed at screening endoscopy. The secondary endpoints are the detection rate of any neoplasm and use of any endoscopic screening. Part III of the study will use samples from participants in study part II to construct a liquid and tissue biobank for the evaluation of less invasive methods of early detection of colon cancer and for the more detailed characterization of the detected neoplasms. Blood, urine, stool, and saliva samples are taken before the endoscopy. Tissue samples are obtained from the neoplasms removed during endoscopy.ResultsA total of 10,568 from 12,000 randomly selected women and men aged 50-54 years living in the Rhine-Neckar-Region of Germany have been invited for participation. The remaining 1432 (11.93%) could not be invited because they reached the age of 55 at the time of contact. Of those invited, 2785/10,568 (26.35%) participated in study part I; 53.60% (1493/2785) of these participants were female. Study parts II and III are ongoing.ConclusionsThis study will answer the question if alternative offers of either screening sigmoidoscopy or screening colonoscopy will increase utilization and effectiveness of endoscopic CRC screening compared with an exclusive offer of screening colonoscopy. In addition, alternative noninvasive screening tests will be developed and validated.Trial RegistrationGerman Clinical Trials Register DRKS00018932; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00018932International Registered Report Identifier (IRRID)DERR1-10.2196/17516

Validation of Microsimulation Models against Alternative Model Predictions and Long-Term Colorectal Cancer Incidence and Mortality Outcomes of Randomized Controlled Trials.

Background. This study aimed to assess the validity of 2 microsimulation models of colorectal cancer (CRC), Policy1-Bowel and ASCCA.Methods. The model-estimated CRC risk in population subgroups with different health statuses, "dwell time" (time from incident precancerous polyp to symptomatically detected CRC), and reduction in symptomatically detected CRC incidence after a one-time complete removal of polyps and/or undetected CRC were compared with published findings from 3 well-established models (MISCAN, CRC-SPIN, and SimCRC). Furthermore, 6 randomized controlled trials (RCTs) that provided screening using a guaiac fecal occult blood test (Funen trial, Burgundy trial, and Minnesota Colon Cancer Control Study [MCCCS]) or flexible sigmoidoscopy (NORCCAP, SCORE, and UKFSST) with long-term follow-up were simulated. Model-estimated long-term relative reductions of CRC incidence (RRinc) and mortality (RRmort) were compared with the RCTs' findings. Results. The Policy1-Bowel and ASCCA estimates showed more similarities to CRC-SPIN and SimCRC. For example, overall dwell times estimated by Policy1-Bowel (24.0 years) and ASCCA (25.3) were comparable to CRC-SPIN (25.8) and SimCRC (25.2) but higher than MISCAN (10.6). In addition, ∼86% of Policy1-Bowel's and ∼74% of ASCCA's estimated RRinc and RRmort were consistent with the RCTs' long-term follow-up findings. For example, at 17 to 18 years of follow-up, the MCCCS reported RRmort of 0.67 (95% confidence interval [CI], 0.51-0.83) and 0.79 (95% CI, 0.62-0.97) for the annual and biennial screening arm, respectively, and the UKFSST reported RRmort of 0.70 (95% CI, 0.62-0.79) for CRC at all sites and 0.54 (95% CI, 0.46-0.65) for distal CRC. The corresponding model estimates were 0.65, 0.74, 0.81, and 0.61, respectively, for Policy1-Bowel and 0.65, 0.70, 0.75, and 0.58, respectively, for ASCCA. Conclusion. Policy1-Bowel and ASCCA's estimates are largely consistent with the data included for comparisons, which indicates good model validity.

Screening For Colorectal Cancer in the Age of Simulation Models: A Historical Lens

Screening For Colorectal Cancer in the Age of Simulation Models: A Historical Lens

Long-term mucosal T cell activation and homing phenotypes in recipients of an Ad5-vectored HIV vaccine

BackgroundVaccine-induced mucosal immune responses may be critical for protection against HIV infection, but may also result in short or long-term changes that enhance susceptibility to infection in some individuals, such as those with baseline seroreactivity to vaccine vector antigens. We examined cellular immune responses in blood and gut mucosal tissue roughly two years following vaccination with placebo or the Step study vaccine MRKAd5/HIV-1. MethodsParticipants vaccinated with either placebo or MRKAd5/HIV-1 during participation in HVTN 071, and HVTN 502/Merck 023 underwent phlebotomy and colonic mucosal biopsies via flexible sigmoidoscopy at two timepoints roughly six months apart. After isolation of mononuclear cells, we compared cellular phenotypes and intracellular cytokine responses in vaccine and placebo recipients with and without baseline serological reactivity to Ad5. ResultsSurface expression of activation and gut-homing markers were elevated on CD4 + and CD8 + gut mucosal mononuclear cells (GMMC) in comparison with PBMC (p < 0.01), but were not significantly affected by baseline Ad5 serostatus or receipt of MRKAd5/HIV-1. ICS responses to stimulation with vaccine antigens were of low frequency and magnitude. Ad5 vector responses were seen in vaccinees and baseline seropositive individuals. CD4 + responses to vector antigens were more common in GMMC than PBMC (p < 0.01) and CD8 + responses to HIV gag insert antigens were more frequent in Ad5 seropositive than Ad5 seronegative individuals (p = 0.03). ConclusionVaccination with the Ad5 vectored candidate HIV vaccine MRKAd5/HIV-1 does not lead to long-term changes in the activation state of mucosal CD4 + or CD8 + T lymphocytes regardless of baseline Ad5 serostatus. The findings of this study do not reveal a basis for enhanced susceptibility to HIV infection two years post vaccination.

Prospective Evaluation of Outpatient Flexible Sigmoidoscopy in Patients With Deep Infiltrating Endometriosis.

To study patients' acceptability of an outpatient flexible sigmoidoscopy (FS) protocol and to assess the diagnostic value of endoscopic assessment in patients with deep endometriosis (DE). All patients with DE and suspected bowel involvement diagnosed were reviewed in the colorectal outpatient clinic before elective surgery following multidisciplinary team meeting discussion. Patients were consented for having the FS performed at the same time of the clinical consultation. Primary outcome was diagnostic value of the FS. Sixty patients were included. Fifty-eight (96.7%) patients consented for the outpatient FS, demonstrating a high rate of patients' acceptability. The sigmoidoscopy demonstrated no abnormalities in 48 patients (82.7%), diverticulosis in 5 patients (8.6%), polyps in 2 patients (3.4%) and mucosal endometriosis in 1 patient only (1.7%). Outpatient FS during the preoperative consultation with the colorectal surgeon is feasible in patients with DE affecting the bowel with a high rate of patients' acceptability but limited additional diagnostic value.

Barriers to flexible sigmoidoscopy colorectal cancer screening in low uptake socio-demographic groups: A systematic review.

To synthesise qualitative evidence related to barriers and facilitators of flexible sigmoidoscopy screening (FSS) intention and uptake, particularly within low socio-demographic uptake groups. FSS uptake is lower amongst women, lower socio-economic status (SES), and Asian ethnic groups within the United Kingdom (UK) and United States of America. A total of 12 168 articles were identified from searches of four databases: EMBASE, MEDLINE, PsycINFO and Web of Science. Eligibility criteria included: individuals eligible to attend FSS and empirical peer-reviewed studies that analysed qualitative data. The Critical Appraisal Skills Program tool evaluated the methodological quality of included studies, and thematic synthesis was used to analyse the data. Ten qualitative studies met the inclusion criteria. Key barriers to FSS intention and uptake centred upon procedural anxieties. Women, including UK Asian women, reported shame and embarrassment, anticipated pain, perforation risk, and test preparation difficulties to elevate anxiety levels. Religious and cultural-influenced health beliefs amongst UK Asian groups were reported to inhibit FSS intention and uptake. Competing priorities, such as caring commitments, particularly impeded women's ability to attend certain FSS appointments. The review identified a knowledge gap concerning factors especially associated with FSS participation amongst lower SES groups. Studies mostly focussed on barriers and facilitators of intention to participate in FSS, particularly within UK Asian groups. To determine the barriers associated with FSS uptake, and further understand how screening intention translates to behaviour, it is important that future qualitative research is equally directed towards factors associated with screening behaviour.

Using Eosinophil Biomarkers From Rectal Epithelial Samples to Diagnose Food Protein-induced Proctocolitis: A Pilot Study.

The gold standard diagnostic procedure for food protein-induced proctocolitis (FPIP) requires flexible sigmoidoscopy (FS). To date there is no validated, noninvasive test to confirm FPIP diagnosis. Eosinophil-derived neurotoxin (EDN), a product of eosinophil (EOS) degranulation, has been shown to correlate with eosinophil infiltration in other tissues. Our objective was to compare EDN concentrations in rectal epithelial samples from infants with FPIP with those from a control population. Children who underwent routine FS at Arnold Palmer Hospital for Children were enrolled in an IRB-approved, prospective, open-label pilot study between July 2017 and May 2019. We obtained rectal epithelial samples via: rectal swab, cytology brushing through FS, and rectal biopsy through FS. We then measured EDN levels in the samples and compared levels found in infants with FPIP against levels found in the control group. FPIP was defined as more than 60 EOS per 10 high-power fields (HPF) in rectal epithelial tissue obtained via rectosigmoid biopsy. Twenty-four patients were enrolled. The control group (n = 13) included patients with normal histopathology (84% boys, mean age 19 months, SD 6 months) and the FPIP group (n = 11) included patients with FPIP confirmed via biopsy (45% boys, mean age 6.9 months, SD 9 months). EDN concentration was significantly higher in the FPIP group than in the control group, for 2 sampling methods: rectal biopsy (183.6 ± 114.6 vs 76.6 ± 71.0 μg/mL; P = 0.010) and rectal swab (66.2 ± 64.8 vs 20.4 ± 22.2 μg/mL; P = 0.025). EDN concentrations measured from rectal swab and rectal biopsy samples is elevated and may be a useful tool to screen for FPIP in children.