Evaluation of an online family history tool for identifying hereditary and familial colorectal cancer.

Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.

Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus.

BACKGROUND: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from decreased mast cell activation and impaired intestinal inflammation. OBJECTIVE: To quantify mast cell activation and inflammation in patients undergoing conventional and minimal invasive surgery. METHODS: (1) Mast cell activation (ie, tryptase release) and pro-inflammatory mediator release were determined in peritoneal lavage fluid obtained at consecutive time points during open, laparoscopic and transvaginal gynaecological surgery. (2) Lymphocyte function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) mRNA as well as leucocyte influx were quantified in non-handled and handled jejunal muscle specimens collected during biliary reconstructive surgery. (3) Intestinal leucocyte influx was assessed by 99mTc-labelled leucocyte single photon emission computed tomography (SPECT) - computed tomography (CT) scanning before and after abdominal or vaginal hysterectomy. RESULTS: (1) Intestinal handling during abdominal hysterectomy resulted in an immediate release of tryptase followed by enhanced interleukin 6 (IL6) and IL8 levels. None of the mediators increased during minimal invasive surgery except for a slight increase in IL8 during laparoscopic surgery. (2) Jejunal ICAM-1 and iNOS mRNA transcription as well as leucocyte recruitment were increased after intestinal handling. (3) Leucocyte scanning 24 h after surgery revealed increased intestinal activity after abdominal but not after vaginal hysterectomy. CONCLUSIONS: This study demonstrates that intestinal handling triggers mast cell activation and inflammation associated with prolonged postoperative ileus. These results may partly explain the faster recovery after minimal invasive surgery and encourage future clinical trials targeting mast cells to shorten postoperative ileus.

Chemokine receptor CXCR3 expression in inflammatory bowel disease.

CD4+ T lymphocytes in the lamina propria (LP) of the gut play a central role in the immune response in inflammatory bowel disease (IBD). CXCR3 is a chemokine receptor expressed on activated T lymphocytes, and a key component for the recruitment of T helper (Th1) effector cells to the site of inflammation. To determine if CXCR3 is involved in localization of T cells to the gut in IBD patients, we investigated the expression of CXCR3 on CD4+ T lymphocytes in the LP and in the submucosa of resection specimens from 51 IBD patients and 15 control patients. Positive cells were microscopically scored using a semiquantitative analysis on a five-point scale. We found that CD4+ T cells, CXCR3+ cells, and CD4+CXCR3+ T cells in the LP were slightly increased in both IBD groups compared with control non-IBD specimens. In addition, CD4+ and CXCR3+ cells in the submucosa were significant increased in the CD group compared with the control group. CD4+ and CXCR3+ expression was not statistically different between CD and UC. Flow cytometry was used to analyze the percentage of CXCR3+ cells within the CD4+ T-cell population isolated from biopsy specimens and peripheral blood from IBD patients and control patients. There was no difference in the percentage of CD4+CXCR3+ cells between the different groups in the gut as well as in the circulation. These results suggest that CD4+CXCR3+ T cells migrate to the normal and inflamed intestinal mucosa, indicating a role in maintaining normal gut homeostasis. The selective expression of CXCR3+ cells in the submucosa of CD patients might also indicate that these cells play a role in inflammation.