Small bowel adenocarcinoma in neoterminal ileum in setting of stricturing Crohn's disease: A case report and review of literature.

BACKGROUND: Small bowel adenocarcinomas (SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn's disease (CD). CD-induced SBA poses diagnostic challenges given overlapping presentation with stricturing CD and lack of diagnostics for early detection. Moreover, guidance is lacking on the impact of recently approved therapeutics in CD on SBA management. Here, we aim to highlight the future of CD-induced SBA management and discuss the potential merit of balloon enteroscopy and genetic testing for earlier detection. CASE SUMMARY: We report the case of a 60-year-old female with longstanding Crohn's ileitis, presenting with acute obstructive symptoms attributed to stricturing phenotype. Her obstructive symptoms were refractory to intravenous (IV) steroids, with further investigation via computed tomography enterography not providing additional diagnostic yield. Ultimately, surgical resection revealed SBA in the neoterminal ileum, with oncologic therapy plan created. However, this therapy plan could not be initiated due to continued obstructive symptoms attributed to active CD. Ultimately, infused biologic therapy was initiated, but her obstructive symptoms continued to remain dependent on IV corticosteroids. Review of diagnostics by a multidisciplinary care team suggested metastatic disease in the peritoneum, lending to a shift in the goals of care to comfort. CONCLUSION: With the diagnostic and therapeutic challenges of concurrent SBA and CD, multidisciplinary care and algorithmic management can optimize outcomes.

Pentosan Polysulfate-Associated Dysplasia in Patients With Inflammatory Bowel Disease: A Case Series.

INTRODUCTION: This study evaluates the potential association of pentosan polysulfate (PPS) with inflammatory bowel disease (IBD) or dysplasia. METHODS: We searched electronic medical records to identify patients with IBD using PPS. RESULTS: Ten of 30 identified patients (33.3%) had colonic dysplasia. Six of them (60%) underwent colectomy for endoscopically unresectable dysplasia. Three (10%) discontinued PPS, each with an apparent benefit. DISCUSSION: Patients with IBD at 2 institutions who had taken PPS had high rates of colonic dysplasia leading to surgery. Patients who stopped PPS showed improvement in their colitis. PPS may play a causal role in the development of colitis and dysplasia.

Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy.

BACKGROUND AND GOALS: Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. METHODS: We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. RESULTS: We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). CONCLUSION: Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.

Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are complex, inflammatory bowel diseases (IBD) with debilitating complications. While severe IBD typically requires biologic agents, the optimal therapy for mild-moderate IBD is less clear. AIMS: To assess the efficacy of thiopurine monotherapy for maintenance of mild-moderate IBD and clinical variables associated with treatment outcome. METHODS: This retrospective study included adults with mild-moderate IBD who were started on thiopurines without biologic therapy. The primary outcome was therapy failure, defined by disease progression based on clinical, endoscopic, and radiologic criteria. Clinical variables were extracted at time of thiopurine initiation. Univariable and multivariable Cox proportional hazards models were used to examine the independent contribution of the clinical variables on treatment response. RESULTS: From 230 CD patients, 64 (72%) were free of treatment failure with mean follow-up of 3.3 years. In our multivariable model, thiopurine failure was associated with concomitant systemic steroid administration (aHR 2.43, p = 0.001), whereas protective factors included concomitant oral 5-aminosalicylic acid (5-ASA) therapy (aHR 0.54, p = 0.02) and non-fistulizing, non-stricturing disease (aHR 0.57, p = 0.047). From 173 UC patients, 50 (71%) were free from treatment failure with mean follow-up of 3.3 years. On multivariable analysis, concomitant oral steroids were associated with thiopurine failure (aHR 2.71, p = 0.001). Only 13 (4%) discontinued thiopurines from adverse effects. CONCLUSIONS: In mild-moderate uncomplicated IBD, thiopurine monotherapy was associated with longitudinal maintenance of remission and may represent a lower-cost, convenient, and effective alternative to biologics. Multiple clinical variables were predictive of treatment response.

Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.

Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin α4ß7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-α4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α4ß7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-ß7) blocks leukocyte trafficking via α4ß7 and cell adhesion via αEß7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α4ß7 IgG2), PN-943 (orally administered and gut-restricted α4ß7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG).

Comparative Incidence of Inflammatory Bowel Disease in Different Age Groups in the United States.

BACKGROUND: Data on the incidence of inflammatory bowel disease (IBD) by age group are available in countries outside of the United States or localized populations within the United States. We aimed to estimate the incidence rates (IRs) of IBD by age group using a US multiregional data set. METHODS: We used the Optum Research Database to identify incident IBD patients with a disease-free interval of 1.5 years between 2005 and 2015. Overall and age-specific IRs were calculated for 4 different age groups: pediatric (0-17 years), young adult (18-25 years), adult (26-59 years), elderly (>60 years). Time trends of incidence were evaluated in each age group. Perianal phenotype (in Crohn's disease [CD]) was also compared. RESULTS: The mean IR for the cohort (n = 60,247) from 2005 to 2015 was 37.5/100,000. The IR was highest in adult and elderly cohorts (36.4 and 36.7/100,000 respectively). In the adult and elderly groups, the IR for UC was higher than that for CD, whereas the opposite was true in the pediatric and young adult groups. The IR increased over the 10-year study period for all age groups (time trends P < 0.001). The elderly group had less perianal disease than the adult group (20.8 vs 22.3%, respectively; P < 0.05). CONCLUSIONS: In one of the most comprehensive evaluations of the incidence of IBD in the United States, we found an incidence rate similar to those of other national populations. We also confirmed differences of specific IBD phenotypes based on age groups, with lower rates of perianal disease in the elderly.

Gender disparities in gastroenterology fellowship director positions in the United States.

BACKGROUND AND AIMS: Despite a paucity of women occupying leadership positions in academic medicine, studies have shown a higher ratio of female representation in the program director position compared with division chief in multiple specialties. This study aims to determine whether this trend exists in 3-year gastroenterology fellowships in the United States and to evaluate for any factors that may affect these differences. METHODS: In 2015, data were collected for the 163 U.S. gastroenterology fellowship programs including program director, associate program director, division chief, gender distribution, program size, academic center affiliation, and geographic region. RESULTS: A higher percentage of men than women held the role of program director (82% vs 18%), associate program director (72% vs 28%), and division chief (93% vs 7%). Women in program leadership held lower academic rank than their male counterparts (P < .0001). The program director was more likely to be female if the division chief also was female (P = .03). Programs with a higher number of trainees tended to be led by a female program director (P = .06). CONCLUSIONS: A gender disparity exists in all gastroenterology leadership roles, although the magnitude is smaller for program director and associate program director than the role of division chief. Further studies are needed to investigate the impact of this disparity on promotion and academic productivity.

The role of a nurse telephone call to prevent no-shows in endoscopy.

BACKGROUND AND AIMS: Preventing missed appointments, or "no-shows," is an important target in improving efficient patient care and lowering costs in gastrointestinal endoscopy practices. We aimed to investigate whether a nurse telephone call would reduce no-show rates for endoscopic appointments, and to determine if hiring and maintaining a nurse dedicated to pre-endoscopy phone calls is economically advantageous. Our secondary aim was to identify predictors of no-shows to endoscopy appointments. METHODS: We hired and trained a full-time licensed nurse to make a telephone call to patients 7 days before their scheduled upper endoscopy or colonoscopy. We compared this intervention with a previous reminder system involving mailed reminders. The effect of the intervention and impact of other predictors of no-shows were analyzed in 2 similar preintervention and postintervention patient cohorts. A mixed effects logistic regression model was used to estimate the association of the odds of being a no-show to the scheduled appointment and the characteristics of the patient and visit. An analysis of costs was performed that included the startup and maintenance costs of the intervention. RESULTS: We found that a nurse phone call was associated with a 33% reduction in the odds of a no-show visit (odds ratio, 0.67; 95% confidence interval, 0.50-0.91), adjusting for gender, age, partnered status, insurer type, distance from the endoscopy center, and visit type. The recovered reimbursement during the study period was $48,765, with net savings of $16,190 when accounting for the maintenance costs of the intervention; this resulted in a net revenue per annum of $43,173. CONCLUSIONS: We found that endoscopy practices may increase revenue, improve scheduling efficiency, and maximize resource utilization by hiring a nurse to reduce no-shows. Predictors of no-shows to endoscopy included unpartnered or single patients, commercial or managed care, being scheduled for colonoscopy as opposed to upper endoscopy, and being scheduled for a screening or surveillance colonoscopy.

Prevalence of Antibodies Against JC Virus in Patients With Refractory Crohn's Disease and Effects of Natalizumab Therapy.

BACKGROUND & AIMS: Natalizumab, a humanized antibody against the α4 integrin subunit, effectively induces and maintains remission in patients with Crohn's disease (CD) refractory to conventional treatments. Progressive multifocal leukoencephalopathy is a rare but fatal brain infection caused by John Cunningham (JC) virus and has been associated with natalizumab use. We assessed the prevalence of and risk factors for antibodies to JC virus in serum of patients with refractory CD who were candidates for, or already were receiving, natalizumab. We also assessed the effects of natalizumab treatment of these patients. METHODS: In a retrospective study, we analyzed clinical charts from 191 patients with CD (74 males; mean age, 38.7 y; mean duration of disease, 14.9 y) tested for serum JC virus antibody from December 2012 through May 2014 at 2 medical centers in the United States. We calculated JC virus antibody prevalence and compared the characteristics of patients who tested negative vs those who tested positive, to identify risk factors. We also assessed the rate of subsequent natalizumab use, surgery, and seroconversion during natalizumab therapy. RESULTS: A total of 129 of the patients (67.5%) tested positive for serum JC virus antibody. Multivariate analysis showed that past use of thiopurine was a risk factor for testing positive for JC virus antibody (odds ratio, 7.8; 95% confidence interval, 2.0-30.4; P = .003). Twenty-two of the patients who tested negative for JC virus antibody (35.5%) and 16 of the 129 patients who tested positive (12.4%) had been treated with natalizumab. Cox regression analysis determined that natalizumab use was the only factor associated with avoiding subsequent surgery (hazard ratio, 0.23; 95% confidence interval, 0.06-0.98). Seroconversion (from testing negative to positive for JC virus antibody) occurred in 1 of the 22 patients (4.5%) who initially tested negative during natalizumab therapy. CONCLUSIONS: The prevalence of CD patients exposed to JC virus is comparable with that of the general population. In this retrospective study, prior thiopurine use was associated with an increased risk for testing positive for JC virus antibody. Natalizumab use reduced the risk of subsequent surgery.

Strictureplasty for Treatment of Crohn's Disease: an ACS-NSQIP Database Analysis.

INTRODUCTION: Strictureplasty is an alternative to resection for treatment of Crohn's disease (CD) strictures. It preserves bowel length, and specialized centers report favorable outcomes. Strictureplasty rates, however, are thought to be low, and it was recently removed from required cases for colon and rectal surgery residents. We examined operative characteristics, and trends in its use using a large national database. MATERIALS AND METHODS: We examined the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2012, identifying patients with CD who underwent strictureplasty. We identified patient characteristics, outcome variables, and trends in utilization of strictureplasty. RESULTS: A total of 9172 patients underwent surgery for CD. Two hundred fifty-six (2.8 %) underwent strictureplasty. Median preoperative albumin was 3.6. Preoperative steroid use and weight loss rates were 39 and 8 %. Rates of wound infection and organ space infection were 11 and 4 %. Rate of reoperation was 6 %. Outcomes did not change significantly over time (all p = NS). The proportion of CD operations that included a strictureplasty decreased from 5.1 to 1.7 % (OR 0.902 with each additional year, 95 % CI (0.852, 0.960), p < 0.001). CONCLUSION: Strictureplasty as treatment for CD is decreasing in the ACS-NSQIP database. Infectious complications and reoperation rates following strictureplasty are low and have not changed over time.

Initial surgical management of ulcerative colitis in the biologic era.

BACKGROUND: The initial minimum operation for ulcerative colitis is a total abdominal colectomy. Healthy patients may undergo proctectomy at the same time; however, for ill patients, proctectomy is delayed. Since the introduction of biologic medications in 2005, ulcerative colitis medical management has changed dramatically. OBJECTIVE: We examined how operative management for ulcerative colitis has changed from the prebiologic to biologic eras. DESIGN: We conducted a retrospective review of data on patients with ulcerative colitis who were included in the Nationwide Inpatient Sample database. SETTINGS: This study was conducted at a single university. PATIENTS: A total of 1,547,852 patients with ulcerative colitis who were admitted to a US hospital from 1991 to 2011 were included in the study. MAIN OUTCOME MEASURES: We examined patients whose initial operation consisted of total abdominal colectomy without proctectomy versus a total proctocolectomy with or without a pouch. We also examined which operation was done at the time of the construction of an ileoanal pouch. Patients who underwent colectomy and pouch construction in the same hospitalization were compared with those who received pouch formation at a subsequent hospitalization. RESULTS: Ulcerative colitis-related admissions rose by 170% during the years examined, and the number of patients who required total abdominal colectomy increased by 44%. Total abdominal colectomy increased by 15%, as opposed to total proctocolectomy (p < 0.001). Pouch construction at a subsequent operation increased by 16% (p = 0.002). Since 2008, total abdominal colectomy has surpassed total proctocolectomy as the most common initial surgical intervention for ulcerative colitis. LIMITATIONS: The Nationwide Inpatient Sample is a retrospective database, and we were limited to examining the variables within it. CONCLUSIONS: Total abdominal colectomy is currently the most common initial operation for patients with ulcerative colitis, and an ileoanal pouch is more frequently constructed at a subsequent hospitalization. These trends coincide with the initiation of biologic treatments and may imply that patients are acutely ill at the time of initial operation. Alternately, there may be surgeon-perceived bias of increased surgical risk or a shift in care to specialized surgeons for pouch construction.

Natalizumab in Crohn's disease: results from a US tertiary inflammatory bowel disease center.

BACKGROUND: Natalizumab is an efficacious agent for the induction and maintenance of remission in patients with Crohn's disease (CD) who have failed anti-tumor necrosis factor (TNF) agents. We aimed to assess the efficacy and safety of natalizumab outside of clinical trial at a US tertiary center. METHODS: Retrospective case review of patients with CD receiving natalizumab. RESULTS: Forty-nine patients with CD (28 women; median age, 33 years) receiving natalizumab from April 2008 to November 2011 were identified. Median duration of disease was 180 months (range, 36-576 months); 40 patients had ileocolonic disease, 1 had ileal disease, and 8 had colonic disease. Twenty-one patients had penetrating disease, and 28 had a history of CD-related surgical treatment. Forty-seven patients previously failed treatment with at least 1 anti-TNF agent. Median duration of natalizumab treatment was 7 months (interquartile range, 3-21.5 months). Twenty-four patients (49%) were continuing natalizumab at the time of this review, and 25 discontinued treatment because of the lack of response, side effects, or positive JC virus antibody. Seventeen patients (35%) successfully continued treatment with natalizumab for longer than 12 months, and nonpenetrating disease phenotype was identified as a predictor of longer response (compared with penetrating phenotype; P = 0.013). Nine patients (18.4%) experienced adverse effects, 5 of which were serious, but no case of progressive multifocal leukoencephalopathy occurred. CONCLUSIONS: This is the largest series of natalizumab-treated patients with CD. Our results show that natalizumab is an efficacious and safe treatment agent for patients refractory to anti-TNF agents and that nonpenetrating disease phenotype has more durable response over time.

Prostate specific antigen screening for prostate cancer: knowledge of, attitudes towards, and utilization among primary care physicians.

OBJECTIVE: Prostate specific antigen (PSA) screening for prostate cancer screening is not uniformly recommended by national organizations or primary care physicians (PCPs). Given this lack of consensus, we sought to identify patterns in physician knowledge of and attitudes towards PSA screening and to determine how these patterns along with patient and provider demographics influence PSA screening practices. METHODS: A self-administered questionnaire, which assessed provider's knowledge of prostate cancer, confidence in his/her knowledge, and PSA screening practices, was mailed to PCPs at an academic medical center. Frequencies of responses were summarized and 3 outcome variables (knowledge, confidence, and propensity to screen) were derived. Association of covariates with the outcome variables was determined using multivariable logistic regression. RESULTS: Eight-two (30.4%) physicians completed the survey; 98% identified African-American race as a prostate cancer risk factor, 42% identified digital rectal exam and PSA as the accepted screening method, and 59% underestimated the likelihood of prostate cancer in a man with a PSA level > 4 ng/ml; 19% were confident in their knowledge of prostate cancer; 86% screened fewer than 60% of their male patients over 50. A knowledge score above the median was not associated with a higher propensity to screen (r = 0.06, P = 0.61). Confidence in one's knowledge was correlated with ordering PSA testing (r = 0.33, P < 0.01). Physician (e.g., ethnicity) and patient (e.g., request for PSA testing) related factors, as well as practice guidelines, particularly those of the US Preventative Services Task Force, influenced providers' decision to offer PSA screening. CONCLUSIONS: Respondents correctly identified prostate cancer risk factors but were less knowledgeable about prostate cancer screening tests and overall prostate cancer risk. Most respondents were not confident in their knowledge and did not screen men over 50. Multiple patient- and provider-specific factors influence the decision to offer or not offer PSA screening.