Keith Sultan

The nature of inflammatory bowel disease in patients with coexistent colonic diverticulosis

Goals/Background Reports of segmental colitis with diverticula regard this entity as a local disease. Our goal was to reexamine the association of diverticula to colitis and question the relationship of colonic diverticulosis with generalized inflammatory bowel disease (IBD). Study A retrospective database review of more than 1600 patients matched 100 cases with IBD and colonic diverticulosis with a control group of 100 patients with IBD without diverticulosis. Patients were matched by gender, IBD diagnosis, and date of birth. Variables examined included disease distribution, strictures, fistulae, extraintestinal manifestations (EIMs), family history, and age at IBD diagnosis. Results For all IBD diagnoses, more sigmoid inflammation occurred in cases with diverticular disease: 82% versus 65% for controls (P=0.005), and in the rectum: 85% versus 69% for controls (P=0.005). In the Crohns disease with diverticulosis subset, sigmoid inflammation was more common: 70% versus 42% for controls (P=0.007), and in the rectum: 70% versus 46% for controls (P=0.02). Disease distribution was otherwise similar throughout the colon, ileum, and jejunum. The incidence of strictures (P=0.99) and fistulae (P=0.69) was similar. EIMs were more frequent in cases with diverticulosis: 28% versus 16% (P=0.05). Family history of IBD was similar: 26% for cases and 16% for controls (P=0.12). Age at IBD diagnosis was significantly greater in diverticulosis cases compared with controls: 51.5 years (±17.6) versus 42.8 years (±17.5) (P<0.001), respectively. Conclusions We observed an increased frequency of sigmoid and rectal inflammation, EIMs, and an older age of IBD onset in cases with diverticulosis. This suggests a role for diverticula in IBD beyond that of a mere coincidental finding.

Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis.

AIM To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal. Two subgroups of patients were compared: group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD. RESULTS Of 115 patients with longstanding UC reviewed, 68 patients met the inclusion criteria. Twenty patients were in group 1 and 48 in group 2. We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation. Overall, histological disease activity in the absence of gross/endoscopic disease was found in 31.2% (95%CI: 28%-35%) of colonoscopies performed on the entire cohort of 68 patients. Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients, 88% (95%CI: 72%-97%) vs 59% (95%CI: 53%-64%). Only 3/20 (15%) of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity (i.e., no endoscopic or histological activity) as compared to 37/48 (77%) of patients in group 2, and only 3.3% (95%CI: 0.09%-8.3%) of colonoscopies in group 1 had no histological inflammation compared to 23% (95%CI: 20%-27%) in group 2. CONCLUSION Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease. Our findings support including the elimination of histological inflammation in the definition of mucosal healing, and support this endpoint as an appropriate goal of therapy because of its risk of increasing dysplasia and colon cancer.

Prognosis of lymphoma in patients following treatment with 6-mercaptopurine/azathioprine for inflammatory bowel disease.

Background: 6‐Mercaptopurine (6‐MP) and azathioprine (AZA) are effective for induction and maintenance therapy of Crohns disease (CD) and ulcerative colitis (UC). There is an increased risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with 6‐MP/AZA. Little, however, is known about the prognosis of IBD patients treated with 6‐MP/AZA who develop lymphoma. Methods: We conducted a retrospective review of 8780 records from three tertiary IBD centers and the records of 600 lymphoma patients from an academic Hematology and Oncology Center. The primary endpoint variable was survival of IBD patients with a lymphoma diagnosis treated or not treated with 6‐MP/AZA. A secondary endpoint was the relative survival rate (by gender, race, and ethnicity) extrapolated from the Surveillance Epidemiology and End Results (SEER) database, computed for each subject. Results: Fourteen IBD patients were diagnosed with lymphoma. Twelve had CD and two had UC. Seven patients had treatment with 6‐MP/AZA and seven had not. Two patients who received 6‐MP/AZA died (both 1 year after diagnosis) and two patients who had not received 6‐MP/AZA died (one after 2 years, another 3 years after diagnosis), all from lymphoma. Survival at last follow‐up was similar to expected survival based on extrapolated SEER data for both 6‐MP/AZA treated and untreated patients. Conclusions: We found no differences of survival with lymphoma between IBD patients and expected survival for the general population. Also, the prognosis for those IBD patients treated with 6‐MP/AZA was not worse than lymphoma patients not treated with 6‐MP/AZA. Statistical analysis, however, was limited by the small sample size and heterogeneity of the patients studied. (Inflamm Bowel Dis 2012)

Comparison of the diagnostic yield and outcomes between standard 8 h capsule endoscopy and the new 12 h capsule endoscopy for investigating small bowel pathology

AIM To evaluate the completion rate and diagnostic yield of the PillCam SB2-ex in comparison to the PillCam SB2. METHODS Two hundred cases using the 8-h PillCam SB2 were retrospectively compared to 200 cases using the 12 h PillCam SB2-ex at a tertiary academic center. Endoscopically placed capsules were excluded from the study. Demographic information, indications for capsule endoscopy, capsule type, study length, completion of exam, clinically significant findings, timestamp of most distant finding, and significant findings beyond 8 h were recorded. RESULTS The 8 and 12 h capsule groups were well matched respectively for both age (70.90 ± 14.19 vs 71.93 ± 13.80, P = 0.46) and gender (45.5% vs 48% male, P = 0.69). The most common indications for the procedure in both groups were anemia and obscure gastrointestinal bleeding. PillCam SB2-ex had a significantly higher completion rate than PillCam SB2 (88% vs 79.5%, P = 0.03). Overall, the diagnostic yield was greater for the 8 h capsule (48.5% for SB2 vs 35% for SB2-ex, P = 0.01). In 4/70 (5.7%) of abnormal SB2-ex exams the clinically significant finding was noted in the small bowel beyond the 8 h mark. CONCLUSION In our study, we found the PillCam SB2-ex to have a significantly increased completion rate, though without any improvement in diagnostic yield compared to the PillCam SB2.

Evolving concepts: how diet and the intestinal microbiome act as modulators of breast malignancy.

The intestinal microbiome plays an important role in human physiology. Next-generation sequencing technologies, knockout and gnotobiotic mouse models, fecal transplant data and epidemiologic studies have accelerated our understanding of microbiome abnormalities seen in immune diseases and malignancies. Dysbiosis is the disturbed microbiome ecology secondary to external pressures such as host diseases, medications, diet and genetic conditions often leading to abnormalities of the host immune system. Specifically dysbiosis has been shown to lower circulating lymphocytes, and increase neutrophil to lymphocyte ratio, a finding which has been associated with a decreased survival in women with breast cancers. Dysbiosis also plays a role in the recycling of estrogens via the entero-hepatic circulation, increasing estrogenic potency in the host, which is another leading cause of breast malignancy. Non-modifiable factors such as age and genetic mutations disrupt the microbiome, but modifiable factors such as diet may also lead to profound disruptions as well. A better understanding of dietary factors and how they disrupt the microbiome may lead to beneficial nutritional interventions for breast cancer patients.

A prospective open-label trial of Remicade in patients with severe exacerbation of Crohn's disease requiring hospitalization: a comparison with outcomes previously observed in patients receiving intravenous hydrocortisone.

Purpose To evaluate treatment response to intravenous (IV) infliximab (IFX) as a first-line therapy in patients hospitalized for severe Crohns disease and compare it with our earlier data using IV hydrocortisone. Methods Seventeen cases received IFX (5 mg/kg) and were matched for the same goal of therapy to those who had received hydrocortisone (300 mg/d). The Crohns and Colitis Foundation of America-International Organization of Inflammatory Bowel Disease (CCFA-IOIBD) score was obtained for the IFX-treated cases on admission and daily and the Crohns disease activity index (CDAI) score weekly throughout the hospitalization and compared with those who received hydrocortisone. Discharge was guided by the same criteria in both groups. Results For the IFX group, the admission mean CCFA-IOIBD score was 13.5 (±4.4). Eight of 17 patients achieved a clinical response with a mean score of 4 (±1.5), representing a ≥50% reduction from baseline to discharge. The mean admission score for the hydrocortisone group was 17.75 (±7.1) with 13 of 16 achieving a mean score of 4.5 (±2.3). The mean discharge score for the 17 IFX patients was 6.9 (±3) and for the hydrocortisone group was 5.9 (±3.2). Median length of hospitalization for the IFX patients was 4 days (range 1 to 9) and 7.5 (5 to 15) days for the hydrocortisone group (P<0.001). Conclusions IFX therapy was an effective first-line agent in patients with severe Crohns disease who require hospitalization and therefore a primary treatment option. Most patients receiving IFX can anticipate a briefer hospitalization than with IV hydrocortisone. Failure of an early response can provide an opportunity to consider an alternate form of therapy sooner with IFX than with hydrocortisone.

Combination therapy for inflammatory bowel disease

Biologic therapies such as infliximab and adalimumab have become mainstays of treatment for inflammatory bowel disease. Early studies suggested that combination therapy (CT) with infliximab and an immunomodulator drug such as azathioprine may help optimize biologic pharmacokinetics, minimize immunogenicity, and improve outcomes. The landmark SONIC trial in Crohn’s disease and the UC SUCCESS trial in ulcerative colitis demonstrated CT with infliximab and azathioprine to be superior to monotherapy with either agent alone at inducing clinical remission in treatment naïve patients with moderate to severe disease. However, many unanswered questions linger. The role of CT in non-naive patients as well as the optimal duration of CT remains unknown. The effectiveness of CT with alternate biologics and/or alternate immunomodulators is not as clear, and it is unknown whether SONIC’s conclusions can be extrapolated beyond infliximab and azathioprine. Also looming are the risks of CT including opportunistic infection and malignancy; specifically, lymphoma. This review lays out the evidence as it pertains to the risks and benefits of CT as well as the areas that require further research. With this information in hand, the practitioner may develop a treatment strategy that best suits each individual patient.

Successful use of volumetric laser endomicroscopy in imaging a rectal polyp

Volumetric laser endomicroscopy (VLE) is second-generation optical coherence tomography (OCT) that is being used for real-time, high-resolution cross-sectional imaging in Barrett’s esophagus [Suter et al. 2008; Yun et al. 2006]. This technology captures images up to 3 mm below the mucosa at a 7 µm resolution in real time. The VLE platform (NvisionVLE™ Imaging System, NinePoint Medical, Bedford, MA, USA) provides real-time, high-resolution cross-sectional imaging using a balloon catheter with scanning optics. This technology has been shown to be sensitive in the detection of dysplasia in Barrett’s esophagus [Evans et al. 2006]. While this technology is being used in the USA in the esophagus, there have been no studies or cases evaluating it in other areas of the gastrointestinal tract. The balloon platform of VLE allows cross-sectional imaging of the gastrointestinal tract if the balloon can collapse the lumen of the area being imaged to allow for adequate scanning of the gastrointestinal tract layers. At our institution, we use VLE routinely for the management of Barrett’s esophagus. We present a case where VLE was used in the rectum in order to provide high-resolution images to help define the anatomy of a neoplastic-appearing polyp prior to surgery. Informed consent has been obtained from the patient discussed in this case report for use of their anonymized details.

Hepatic manifestations of non-steroidal inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is composed of Crohns disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects.

Clinical Markers of Crohn’s Disease Severity and Their Association With Opiate Use

Background The safety of opiate use for patients with Crohn’s disease (CD) has long been a concern. The recent Crohn’s therapy, resource, evaluation, and assessment tool (TREAT) registry update has added to these concerns by demonstrating an association of opiate use with an increased risk of infection and death in CD. While the association is clear, the relationship of opiates to these negative outcomes is not. It is unknown whether opiates are a contributing factor to these negative outcomes or if their use is merely a marker of more severe disease. We hypothesized that opiate use is not harmful in CD but is a marker of disease severity and would be associated with commonly accepted clinical markers of severe CD such as early age at CD onset, disease duration, small intestinal involvement, a history of fistula or stricture, and lower quality of life (QOL) scores. Methods Data on CD history including pain medication usage were obtained from an interviewer directed survey of patients admitted to two tertiary care hospitals over a 2-year period. CD as the primary admitting diagnosis was not required. Active opiate use was defined by usage within the past month prior to admission. Results A total of 133 patients were approached to participate, of whom 108 consented to the survey, and 51 were active opiate users. Opiate using CD patients were more commonly smokers (22% vs. 3.45%, P < 0.010), had fistulas (40% vs. 22.4%, P < 0.048) and had a poorer quality of life score by short form inflammatory bowel disease questionnaire (mean 3.80 vs. 4.34, P < 0.036) than non-opiate users. No difference was found between opiate users and non-users for age of diagnosis, disease duration, or a history of strictures. Conclusions The study findings demonstrate that opiate use in CD is associated with markers of disease severity including fistulas, smoking, and lower QOL scores. The findings suggest that opiates may not be directly harmful to patients with CD, but may merely be another marker of disease severity. However, given opiates unproven benefits for long term CD pain control and risk of dependence, caution should still be exercised in their use.