From random to precise: updated colon cancer screening and surveillance for inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC). The pathogenesis of CRC in IBD differs from sporadic cancer, with the burden of inflammation being an important contributing factor. Other risk factors for developing CRC in patients with Crohn's disease (CD) or ulcerative colitis (UC) includes a family history of CRC, personal history of dysplasia, history of strictures, or primary sclerosing cholangitis (PSC). Dysplasia is the precursor of cancer and ensuring effective surveillance strategies is vital for early detection and intervention. In the past, dysplasia detection relied on random biopsies, but recent studies have shown that, with the adaptation of high-definition white light endoscopy (HD-WLE), dye sprayed chromoendoscopy (DCE) and virtual chromoendoscopy (VCE), dysplasia detection has improved. While there exists a certain degree of consensus amongst experts regarding the management of dysplasia, it is important to implement a personalized approach to each patient's care. Our review focuses on advancements in the past two decades, specifically highlighting the modifications that have been implemented since the SCENIC guidelines. It also explores future directions, including the potential implementation of stool studies as a non-invasive tool for surveillance and the emerging role of artificial intelligence (AI) in dysplasia detection.

Trends in hospital admissions and mortality among inflammatory bowel disease patients with substance use disorder: a 10-year United States nationwide analysis.

Background: Patients with inflammatory bowel disease (IBD) and substance use disorder (SUD) may have worse clinical outcomes. However, data specific to the hospital admission and mortality rates among IBD patients with SUD are scarce. Our objective was to assess trends in admission, healthcare expenses, and mortality for IBD patients with SUD. Methods: We conducted a retrospective study using the National Inpatient Sample database to analyze SUD (alcohol, opioids, cocaine, and cannabis) among IBD hospitalizations from 2009 to 2019. Results: A total of 132,894 hospitalizations for IBD had a secondary diagnosis of SUD. Of these patients, 75,172 (57%) were men and 57,696 (43%) were women. The IBD-SUD cohort had a longer length of stay than the non-SUD cohort (P < 0.001). The mean inpatient charges for IBD hospitalizations with SUD increased from $48,699 ± $1374 in 2009 to $62,672 ± $1528 in 2019 (P < 0.001). We found a 159.5% increase in IBD hospitalizations with SUD. The hospitalization rate increased from 3492 per 100,000 IBD hospitalizations in 2009 to 9063 per 100,000 in 2019 (P < 0.001). In-hospital mortality for IBD hospitalizations with SUD increased by 129.6% (from 250 deaths per 100,000 IBD hospitalizations in 2009 to 574 deaths per 100,000 IBD hospitalizations in 2019) (P < 0.001). Conclusions: Over the last decade, there has been a rise in IBD hospitalizations with SUD. This has resulted in a longer length of stay, higher inpatient charges, and higher mortality rates. Identifying IBD patients potentially at risk for SUD by screening for anxiety, depression, pain, or other factors has become crucial.

Substance abuse and inpatient outcomes in inflammatory bowel disease hospitalizations in the United States: a propensity matched analysis.

Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammation resulting in a genetically susceptible population. The present study aimed to look at the effect of substance abuse on IBD hospitalizations in the United States. Methods: We identified primary IBD hospitalizations with substance abuse using the National Inpatient Sample database (2016-2019). A matched comparison cohort of IBD hospitalizations without substance abuse was identified by 1:N propensity score matching using the nearest-neighbor method, based on demographics, hospital-level factors, and comorbidities. Results: We matched 4437 IBD hospitalizations with a diagnosis of substance abuse to 4528 hospitalizations without abuse. The median age was higher in the substance abuse group than no abuse (44 vs. 38 years, P<0.001). There was a higher prevalence of discharge to care facilities (2.9% vs. 2.2%) and against medical advice (4.9% vs. 1.8%) in the substance abuse group compared to the no abuse (P<0.001). The median length of hospital stays (LOS) (P=0.74) and hospitalization charge did not differ significantly (P=0.57). There was no significant difference in 30-day inpatient mortality among cohorts (adjusted hazard ratio 0.74, 95% confidence interval 0.32-1.81; P=0.54). There was a higher prevalence of psychoses (2.5% vs. 1.3%) and depression (18.8% vs. 15.7%) in IBD hospitalizations with substance abuse compared to those without abuse (P<0.001). Conclusions: This study reports no difference in median LOS, hospitalization charge, or mortality risk in IBD hospitalizations based on substance abuse. There is a higher prevalence of psychoses and depression in IBD patients, requiring screening for substance abuse to improve overall outcomes.

Influence of Pharmaceutical Direct-to-Consumer Advertisement on Medical Treatment of Inflammatory Bowel Disease-An Outpatient Survey-Based Study.

Background: The management of inflammatory bowel disease (IBD) has become much more complex as our understanding of the disease pathology has improved and as new novel therapeutic options come into play. A factor that has not been studied in the management of this disease is the role that Direct-To-Consumer Advertisement (DTCA) plays in patients' decisions regarding their treatment options. Here we investigate the very role this mode of television advertisement has on influencing our patients. Methods: Following formal institutional review board approval, we devised a prospective, single institution, survey-based study in our university-based outpatient gastroenterology clinic. Surveys included major demographic features along with questions pertaining to patients' interactions with various advertisements. Surveys were collected over a 3-month period. Results: Overall, 103 surveys were collected. The data were not normally distributed. Fifty-three patients were female, and 40 patients were male. Eighty-one percent of patients with IBD were not affected in any way by advertisements with regard to influencing their decision to start new therapies. A subgroup analysis revealed that various parameters including age, sex, and marital status played a role in how DTCA influences patients with regard to their IBD treatments. Discussion: This study demonstrates that overall patients are not significantly influenced by DTCAs; however, some cohorts are influenced in more ways than others. This study highlights the importance of understanding the role DTCA plays in influencing our patients with IBD and sets the foundation for further inquiry into this very interesting relationship.

The impact of corticosteroid use on inpatients with inflammatory bowel disease and positive polymerase chain reaction for Clostridium difficile.

BACKGROUND/AIMS: Optimal management of inflammatory bowel disease (IBD) with concomitant Clostridium difficile infection (CDI) is controversial, especially when CDI diagnosis is made by polymerase chain reaction (PCR) testing, which may reflect colonization without infection. METHODS: We performed a multicenter review of all inpatients with IBD and PCR diagnosed CDI. Outcomes included length of stay, 30- and 90-day readmission, colectomy during admission and within 3 months, intensive care unit (ICU) admission, CDI relapse and death for patients who received corticosteroid (CS) after CDI diagnosis versus those that did not. Propensity-adjusted regression analysis of outcomes based on CS usage was performed. RESULTS: We identified 177 IBD patients with CDI, 112 ulcerative colitis and 65 Crohn's disease. For IBD overall, CS after CDI diagnosis was associated with prolonged hospitalization (5.5 days: 95% confidence interval [CI], 1.5-9.6 days; P=0.008), higher colectomy rate within 3 months (odds ratio [OR], 5.5; 95% CI, 1.1-28.2; P=0.042) and more frequent ICU admissions (OR, 7.8; 95% CI, 1.5-41.6; P=0.017) versus no CS. CS use post-CDI diagnosis in UC patients was associated with prolonged hospitalization (6.2 days: 95% CI, 0.4- 12.0 days; P=0.036) and more frequent ICU admissions (OR, 7.4; 95% CI, 1.1-48.7; P=0.036). CONCLUSIONS: CS use among IBD inpatients with CDI diagnosed by PCR is associated with poorer outcomes and would seem to reinforce the importance of C. difficile toxin assay to help distinguish colonization from infection. This adverse effect appears more prominent among those with UC.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

BACKGROUND: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). METHOD: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. RESULTS: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. CONCLUSION: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise.

Acute Mesenteric Ischemia Caused by Rare Cardiac Tumor Embolus.

Acute mesenteric ischemia (AMI) is a rare vascular emergency associated with a high mortality rate. The most common cause of AMI is cardiac emboli from thrombi associated with atrial fibrillation or following myocardial infarction. We present a case of AMI caused by a unique source of emboli, confirmed as an embolization of a cardiac sarcoma to the small bowel by matching biopsies obtained from the superior mesenteric artery (SMA) and the embolic source.

Association of smoking and flat adenomas: results from an asymptomatic population screened with a high-definition colonoscope.

BACKGROUND: Flat adenomas represent a morphologically distinct class of polyps that may be difficult to detect, and little is known regarding risk factors for these lesions. Identification of risk factors for these lesions may aid in colorectal cancer (CRC) screening, because patients at risk for these lesions may require special imaging techniques. Smoking, an important risk factor for CRC, may be associated with molecular changes that increase the risk for flat adenomas. OBJECTIVE: The aim of this study was to examine the association between smoking and flat adenomas. DESIGN: Prospective cross-sectional study. SETTING: University hospital endoscopy center. PATIENTS: We enrolled asymptomatic patients presenting for CRC screening. INTERVENTIONS: We screened patients with a high-definition (1080i signal) wide-angle (170 degrees field of view) Olympus 180-series colonoscope. We collected demographics, medication use, family history of CRC, diet history, and smoking history. MAIN OUTCOME MEASUREMENTS: Polyp morphology, assessed by using the Japanese Research Society Classification (JRSC). RESULTS: A total of 600 patients were enrolled. We observed that smoking was associated with having a flat adenoma of any size (adjusted odds ratio [OR], 2.53; 95% CI, 1.60-4.00), having only flat adenomas that were > or = 6 mm in diameter (adjusted OR, 3.84; 95% CI, 2.02-7.32), as well as flat advanced adenomas (adjusted OR, 2.81; 95% CI, 1.08-7.30). LIMITATIONS: The study design may not account for some confounding variables and provides no information regarding smoking status at the time of initiation of flat adenomas. CONCLUSION: Smoking was associated with flat adenomas in our population. Our findings may explain the earlier onset of CRC in smokers as well as the advanced stage with which they present, with compared with nonsmokers. Smokers may require screening with high-definition colonoscopes to detect flat adenomas.

Body mass index as a predictor of colorectal neoplasia in ethnically diverse screening population.

BACKGROUND: Recent guidelines from the American College of Gastroenterology for screening for colorectal cancer have included obesity as an important risk factor. The recommendation for screening obese people at earlier age was tempered by the need for more data regarding obesity and colorectal neoplasia. AIMS: We designed a cross-sectional study to further examine the predictive value of obesity for colorectal adenomas in asymptomatic patients. METHODS: We prospectively collected demographic, medical, lifestyle, and dietary history from asymptomatic patients presenting for screening colonoscopy. Patients underwent complete colonoscopy using high-definition colonoscope to detect colorectal adenomas. We defined advanced neoplasia as large (≥ 1 cm) adenoma, villous adenoma, high-grade dysplasia or cancer. RESULTS: Six hundred patients with median age of 56 years completed the study. Over 40% of these patients did not consider themselves Caucasian, and less than 5% had a first-degree relative with colorectal cancer. Overall, 40 patients (6.7%) had advanced neoplasia and 216 (36.3%) had any adenoma. There were 185 obese patients (30.8%), who had a prevalence of 44.3% for any adenoma and 13.0% for advanced neoplasia. After multivariate analysis, obesity [body mass index (BMI) ≥ 30 kg/m(2)] was significantly associated with increased risk of advanced neoplasia [odds ratio (OR) = 3.83; 95% confidence interval (CI): 1.94-7.55]. CONCLUSIONS: Obesity was associated with advanced neoplasia in this screening population. Our data regarding the association of colorectal neoplasia with this modifiable risk factor has implications for screening and prevention of colorectal cancer.

Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis.

BACKGROUND: 5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC. OBJECTIVE: To summarize current data on balsalazide and to discuss its impact on management of UC. METHODS: A systematic review of published literature was performed on PubMed using the search terms 'Balsalazide' and 'Colazal(TM)'. The Cochrane database was also reviewed. RESULTS: Balsalzide, a 5-ASA prodrug, ulilizes azoreduction by colonic bacteria to achieve a sustained release of active 5-ASA throughout the colon. A recent clinical trial has demonstrated balsalazide 6.7 g/day to be superior to placebo in inducing remission in symptomatic UC. The drug is well tolerated with a safety profile comparable to other oral 5-ASA agents. The current data suggests that symptomatic remission occurs with both greater swiftness and greater frequency when compared with mesalamine. CONCLUSION: Balsalazide is approved for the treatment of mild-to-moderate active UC. It is efficacious for the induction of remission in mild to moderate UC and has a favorable safety profile, with the added advantages of greater efficacy of remission induction and rapidity of onset.

Incidence of neoplasms in patients who develop sustained leukopenia during or after treatment with 6-mercaptopurine for inflammatory bowel disease.

BACKGROUND & AIMS: Studies to date have not confirmed an association between neoplasms and inflammatory bowel disease (IBD) treated with 6-mercaptopurine (6-MP). We have observed the occurrence of some neoplasms in IBD patients who developed sustained leukopenia as a result of treatment with 6-MP. As a result, we sought to compare the incidence of neoplasms in patients who developed sustained leukopenia after taking 6-MP compared with patients treated with 6-MP without sustained leukopenia. METHODS: A database containing the medical records of more than 600 patients treated with 6-MP for IBD at 1 center between 1965 and 2002 was searched. The patients were divided into 2 groups. The study group consisted of patients who developed sustained leukopenia, defined as a white blood cell count of less than 4000 for 20 or more days. The control group patients matched those in the study group for age and sex. There were 3 matched controls for each patient in the study group. RESULTS: Eighteen patients developed sustained leukopenia and, of these, 4 developed neoplasms (22%)-2 leukemias, 1 non-Hodgkin's lymphoma, and 1 breast cancer. Of the 54 patients in the control group, 4 developed neoplasms (7%) (P = .10). Post hoc analysis revealed a statistically significant difference in the number of hematologic malignancies in the group with sustained leukopenia (P = .014). There was no significant difference between the 2 groups for all confounding variables examined. CONCLUSIONS: There was a trend toward a greater number of total malignancies in the sustained leukopenic patients. The data suggest that it is those patients who develop sustained leukopenia while taking 6-MP/azathioprine who are most at risk.

Complications of pregnancy and child development after cessation of treatment with 6-mercaptopurine for inflammatory bowel disease.

PURPOSE: 6-Mercaptopurine (6-MP) has proven efficacy in the therapy of inflammatory bowel disease. Its teratogenicity is demonstrated in animal studies when used at very high doses, whereas human data suggest that 6-MP at maintenance doses is safe. We report the outcome of 72 pregnancies in patients with inflammatory bowel disease who were previously treated with 6-MP with three different doses of 50, 75, and 100 mg/d, for a median duration of 18 months, along with long-term follow-up of the children. METHODS: We have compared the outcome of pregnancies and development of the offspring in the following two groups: group 1, patients with inflammatory bowel disease who conceived 6 months to 22 years after stopping 6-MP (median 72 months); and group 2, patients with inflammatory bowel disease who never received 6-MP prior to conception. All pregnancies were evaluated in terms of outcome: live full-term birth, premature delivery, stillbirth, spontaneous abortion, ectopic pregnancy, and therapeutic dilatation and curettage. Data on children were obtained regarding birth weight, congenital anomalies, and development. RESULTS: Group 1 included 72 pregnancies carried by 29 women. There were 51 live births (4 premature), 16 spontaneous abortions, 1 stillbirth, 2 therapeutic abortions due to abnormal amniocentesis, and 2 ectopic pregnancies. The total incidence of fetal loss was 29.2%. In group 2, 75 women had 140 pregnancies resulting in 120 live births (8 premature), 18 spontaneous abortions, and 2 stillbirths. There were no cases of ectopic pregnancies or abnormal amniocentesis. The total incidence of fetal loss was 14.3%. There was no increase in the incidence of developmental defects when the mothers had been treated with 6-MP prior to pregnancy. CONCLUSIONS: The incidence of fetal loss is higher in women with inflammatory bowel disease who had been previously treated with 6-MP compared with those who had not. Whether this was related to the older age at conception in 6-MP group, longer duration of disease, initially more severe disease, or use of 6-MP we cannot tell.

Inflammatory Bowel Disease During Pregnancy.

The management of both male and female patients with inflammatory bowel disease (IBD) who wish to have a baby is challenging. For women, the most important factor to bear in mind is that the outcome of pregnancy is largely influenced by disease activity at the time of conception. Women with quiescent disease are likely to have an uncomplicated pregnancy with the delivery of a healthy baby, whereas women with active disease are more likely to have complications such as spontaneous abortions, miscarriages, stillbirths, and exacerbation of the disease. This is more true of patients with Crohn's disease than of patients with ulcerative colitis. Although the safety of medications used during pregnancy is an important issue, the impact of the medications used to treat IBD is less important in comparison to disease activity itself. 5-Aminosalicylic acid (5-ASA) products appear to be safe during pregnancy; corticosteroids are probably safe; 6-mercaptopurine and azathioprine should be used with caution; and methotrexate is contraindicated. There are inadequate data on the use of infliximab during pregnancy. In regard to men with IBD, the disease itself does not seem to have any negative impact on fertility. However, there is controversy about the effects of using 6-mercaptopurine and azathioprine prior to and during fertilization. In view of possible adverse pregnancy outcomes, it would be prudent to withhold 6-mercaptopurine and azathioprine therapy in men with IBD for 3 months prior to conception, when feasible. Most IBD medications should be continued before, during, and after pregnancy, with careful attention to the known cautions and exceptions. If IBD in a pregnant patient is in remission, the prognosis for pregnancy is the same as if she did not have IBD. Active disease should therefore be treated aggressively and remission accomplished before pregnancy is attempted. Similarly, a woman who unexpectedly becomes pregnant while her IBD is active should be treated aggressively, as remission remains the greatest investment for a favorable pregnancy outcome.