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. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved

A Randomized, Placebo Controlled, Double Masked Phase IB Study Evaluating the Safety and Antiviral Activity of Aprepitant, a Neurokinin-1 Receptor Antagonist in HIV-1 Infected Adults

Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic.We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3) and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days.Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20), -0.05(-0.21,+0.10), and +0.04(-0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred.Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity.ClinicalTrials.gov NCT00428519

The effect of 6-mercaptopurine on natural killer-cell activities in Crohn's disease

Crohn's disease patients on long-term 6-mercaptopurine therapy (more than 4 months) were evaluated for activity of peripheral blood natural killer cells. Natural killer-cell cytolytic activity against K-562 tumor-cell targets was examined, as was natural killer-cell suppression of lymphoblastoid B-cell antibody production. In addition, these patients were studied for their ability to generate antitetanus-specific IgG antibody-producing lymphoblastoid B cells following in vivo booster immunization. Crohn's disease patients on 6-mercaptopurine therapy had significant reductions in peripheral blood natural killer-cell activity against K-562 targets compared to normals, disease controls, and Crohn's disease patients not on 6-mercaptopurine. Natural killer-cell suppression of lymphoblastoid B-cell antibody production was like-wise decreased in 6-mercaptopurine-treated patients compared to normal controls. In contrast, the in vivo generated lymphoblastoid B-cell antibody responses of Crohn's disease patients on 6-mercaptopurine therapy were not decreased compared to normal, while Crohn's disease patients not on 6-mercaptopurine therapy had significantly impaired IgG antitetanus antibody responses. These findings suggest that 6-mercaptopurine therapy in Crohn's disease affects several lymphoid subpopulations, resulting in a decreased natural killer-cell cytotoxic activity against K-562 target cells and a decreased natural killer-cell ability to suppress lymphoblastoid B-cell antibody production, as well as an improved humoral immune response following tetanus toxoid booster immunization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44846/1/10875_2004_Article_BF00915512.pd

Inflammatory bowel disease: past, present, and future

Crohn’s disease and ulcerative colitis, collectively known as the inflammatory bowel diseases (IBD), are largely diseases of the twentieth century, and are associated with the rise of modern, Westernized industrial society. Although the causes of these diseases remain incompletely understood, the prevailing model is that the intestinal flora drives an unmitigated intestinal immune response and inflammation in the genetically susceptible host. A review of the past and present of these diseases shows that detailed description preceded more fundamental elucidation of the disease processes. Working out the details of disease pathogenesis, in turn, has yielded dividends in more focused and effective therapy for IBD. This article highlights the key descriptions of the past, and the pivotal findings of current studies in disease pathogenesis and its connection to medical therapy. Future directions in the IBD will likely explicate the inhomogeneous causes of these diseases, with implications for individualized therapy

Rectal mucosal dysplasia in Crohn's disease.

Serial sections of 812 rectal biopsy specimens from 356 Crohn's disease patients were analysed for mucosal epithelial dysplasia. Dysplasia was found in 18 patients (5%), with four showing dysplasia on repeat biopsy specimen. In these 22 biopsy specimens the dysplasia was mild in 13, moderate in nine, and severe in none. Subsequently, three patients (17%) developed neoplasms including carcinoma in two and an adenomatous polyp in one. In colectomy specimens which showed dysplasia, significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia (p less than 0.001). Thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer. Four carcinomas developed in patients with Crohn's disease who did not have dysplasia on rectal biopsy specimen

Observations on the neglect of anal skin tags as an early marker of crohn’s disease in children

© 2020, Shugar Publishing Inc.. All rights reserved. Anorectal skin tags (ASTs) are a common, asymptomatic, early manifestation of Crohn’s disease (CD). Usually CD has its onset in childhood (age 18 or younger). This paper aims to identify patients with Crohn’s disease and ASTs, to determine the age of onset of CD, and then estimate the years that ASTs had been present before establishing the diagnosis of CD. Methods From our database of over 3000 patients with inflammatory bowel disease, we identified 263 Crohn’s disease patients with obvious ASTs at first visit for CD, and 57 (21.6%) of these were in patients diagnosed with CD at age 18 or younger. Results In this group of 57 children, the median age at diagnosis of CD was 14 and the median number of years from the first awareness of ASTs was 6. Conclusions The high incidence of ASTs should encourage pediatricians, internists, family physicians and gastroenterologists to spread the buttocks and search for ASTs in children presenting with diarrhea, rectal bleeding, abdominal pain or growth failure. Accordingly, the diagnosis CD might be made so much earlier and effective medical therapy be initiated sooner

Crohn\u27s disease and acute leukocytoclastic vasculitis of skin.

A 39-yr-old white male with a prolonged history of Crohn\u27s disease presented with worsening diarrhea associated with an increasingly painful rash of both lower extremities as well as left ankle swelling. A skin biopsy revealed an acute leukocytoclastic vasculitis. Intravenous hydrocortisone followed by oral prednisone achieved a rapid remission of the both cutaneous and gastrointestinal manifestations. Long-term remission has been maintained with 6-mercaptopurine and mesalamine. The rare association between cutaneous vasculitis and Crohn\u27s disease is discussed and earlier reported cases reviewed