Vedolizumab Levels in Breast Milk of Nursing Mothers With Inflammatory Bowel Disease.

INTRODUCTION: There are no data on the transfer of vedolizumab in breast milk of nursing mothers. We aimed to assess the presence of vedolizumab in breast milk of nursing inflammatory bowel disease [IBD] patients. METHODS: This was a prospective observational study of vedolizumab-treated breastfeeding patients with IBD. Serum and breast milk samples were obtained at pre-defined tim -points. The in-house developed enzyme-linked immunosorbent assay [ELISA] for measuring vedolizumab in blood was adapted and validated for measurement of the drug in breast milk. The level of vedolizumab was also measured in breast milk of a control group of nursing healthy mothers. RESULTS: Vedolizumab was undetectable in breast milk in IBD patients before the first infusion of vedolizumab [n = 3] and in all of the healthy controls [n = 5]. Vedolizumab was measurable in all lactating women who received vedolizumab [n = 5]. However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng/ml, which was roughly 1/100 of the comparable serum levels. CONCLUSIONS: Vedolizumab can be detected in the breast milk of nursing mothers. Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant.

[Prevention and early detection of colorectal cancer in average risk population--summary of a meeting and the Israeli gastroenterology policy].

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality, with a lifetime risk of 5-6% and mortality rate of nearly 50%. About 75% of the cases occur in average-risk individuals. CRC ideally fulfills the criteria for organizing a mass-screening program: It is common and lethal, cancer is preceded by a pre-malignant lesion (adenoma) and transition from precursor to malignancy develops over years, providing an opportunity for intervention. It is well established that removal of adenomas (polypectomy) prevents CRC and CRC-related death in up to 90% of the cases. In Israel, we lack a clear policy for CRC screening and prevention by the health authorities. A meeting on this subject was held at the Israel Cancer Association, attended by the Minister of Health and leading figures in gastroenterology, oncology and public health. AIMS: To summarize the meeting and the Israeli Gastroenterology Association policy. SUMMARY: Current data on fecal occult blood test, sigmoidoscopy, and colonoscopy was presented, including the reduction of cancer incidence and mortality, safety and cost-effectiveness of each modality. Worldwide and Israeli results on colonoscopy in average-risk persons age 50-75, demonstrated a considerable prevalence of neoplasia, a low morbidity rate, no mortality and a high cost-effectiveness. Based on these results and the literature evidence of up to 90% reduction of CRC mortality following colonoscopy, CRC justifies all the criteria for organizing a prevention program by the health authorities for average-risk population age 50-75. Screening colonoscopy for CRC prevention should be included in this program.

The expression of iNOS and nitrotyrosine in colitis and colon cancer in humans.

Chronic inflammation increases the risk of development of several types of malignancies including colon cancer. It also represents a paradigm for the connection between inflammation and cancer in terms of epidemiology and mechanistic studies in preclinical models. A key component of inflammation promoting cancer is the transcription factor NF-κB, which is known to play a critical role in the regulation of the inducible nitric oxide synthase (iNOS) gene. iNOS is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation and tumorigenesis, the role of iNOS activity in these diseases is still not well understood. Analysis of human biopsies of colitis and colon cancer using immunohistochemistry revealed elevated iNOS protein expression levels, which were strongly paralleled by increased expression of nitrotyrosine suggesting that iNOS has been highly activated in these tissues. These results were corroborated in an in vitro study showing the presence of high iNOS levels in a colon cancer cell line (HT-29) following inflammatory stimuli (TNF-α, peroxynitrite). In addition, the involvement of metastatic processes in the colon biopsies was assessed by means of in situ zymography of MMP activation. MMP 2 (gelatinase A) activation was higher in histopathological sections of colitis and cancer compared to controls. Overall, these data strengthen the findings that in inflammation and colon cancer in humans, iNOS expression and tyrosine nitration may be an indicator of cancer development and progression.