Complex changes of circadian proteins expression in inflammatory bowel disease.

OBJECTIVES AND BACKGROUND: Recently, a possible role of circadian system in the pathogenesis of various gastrointestinal disorders gained an attention. The association of circadian system with immune system activity and reciprocal connection with intestinal microbiota indicate possible links with inflammatory bowel diseases (IBD). METHODS: The retrospective study provided a semiquantitative immunohistochemical analysis of the expression of 8 core circadian proteins (BMAL1, BMAL2, PER1, PER2, PER3, CLOCK, NPAS2 and TIMELESS) in the epithelial cells of intestinal mucosa in 24 patients with Crohn's disease (CD) and 26 patients with ulcerative colitis (UC). Samples from patients without history of IBD served as the control. The BMAL1 protein expression in intramucosal inflammatory cells was explored as well. RESULTS: The expression of 5 core circadian proteins (BMAL1, PER1, PER3, TIMELESS and NAPS2) was decreased in mucosal epithelium of patients with IBD in comparison with the control samples, whereas the expression of BMAL1 and PER1 was more noticeably decreased in UC patients and PER3, TIMELESS and NPAS2 in CD patients. There was a decreased BMAL1 expression in intramucosal inflammatory cells of IBD patients. CONCLUSION: Decreased core circadian proteins expression in colonic mucosa and in intramucosal inflammatory cells of IBD patients indicated a circadian rhythm deregulation as contributing factor in the development of IBD. To our knowledge, this is so far the most extensive immunohistochemical analysis performed on the samples of IBD patients evaluating the changes in circadian protein expression in the intestinal mucosa (Tab. 1, Fig. 2, Ref. 31).

MRI­based neoadjuvant therapy indication in middle and low rectal cancer.

OBJECTIVE: The aim of this study was to evaluate the indication of neoadjuvant therapy in patients with middle and low rectal cancer based on MRI examination. BACKGROUND: In spite of noticeable advances in the diagnosis of rectal cancer, the optimal treatment remains highly debated. Current guidelines advise the use of neoadjuvant therapy in UICC stage II patients or higher. However, in clinical praxis, there is gradual implementation of new criterions and variables used in rectal cancer stage evaluation, the fact of which influences the treatment choice. The most important emerging variables taken currently into account are the distance from mesorectal fascia, circumferential resection margin, extramural venous invasion and intersphincteric plane, all of which can be evaluated using the MRI examination. METHODS: The accuracy of MRI staging was compared with definite histopathological results from resected tumors. Patient data were prospectively collected between the years 2013 and 2018 at 3rd Surgical Clinic, Faculty of Medicine, Comenius University in Bratislava, Slovakia. Data from 101 patients were gathered and divided into two groups, according to the localization of tumor within rectum, while 9 patients were excluded from the study because of benign lesion diagnosis based upon final histopathologic evaluation. RESULTS: In 92 evaluated patients, no significant change was noted between MRI and histopathological T-staging. However, in N-staging, significant differences were noted between preoperative MRI staging and postoperative histopathological staging. CONCLUSION: The results of this study demonstrate inefficient preoperative lymph node staging, suggesting overtreatment of rectal cancer patients. Although the use of neoadjuvant therapy has led to great advances in modern cancer treatment, it is connected with a number of side effects and therefore should be indicated only for patients who can benefit from this treatment (Tab. 1, Fig. 3, Ref. 16).

Significance of MRI in rectal carcinoma therapy optimization - correlation of preoperative T- and N-staging with definitive histopathological findings.

In past decades, both prognosis and therapy of rectal cancer patients showed significant improvement, on the other hand, the incidence of rectal carcinoma continues to have a rising tendency. According to current UICC classification, patients in stage II rectal cancer or higher are indicated for neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) is currently the most common diagnostic method used for preoperative staging of rectal cancer. Several studies already pointed out the inaccuracy of preoperative lymph node staging in patients with rectal cancer. The present study analyzed overall accuracy of MRI staging of rectal cancer and thus its accuracy in neoadjuvant therapy indication, by comparing preoperative MRI staging with definitive histopathologic results from resected tumors. This study evaluated cases of 92 patients with rectal tumor that underwent MRI examination followed by surgical resection. Tumors included in the analysis were ranging from T1 to T3b according to TNM staging, with free circumferential resection margin (CRM), distance form mesorectal fascia more than 5 mm, negative intersphincteric plane and also negative extramural venous invasion (EMVI), while the N stage was not decisive. In all cases both N-staging and T-staging were evaluated histologically and compared with preoperative MRI results. Significant difference in preoperative and postoperative N-staging was shown in 51 patients (61.45%). In majority of cases MRI lead to overstaging, which was observed in 44 cases (53.1 %), with complete negativity of lymph nodes proven by histological examination in 34 cases. On the other hand, understaging of lymph nodes was observed only in 7 cases (7.4 %). The T-staging did not show significant differences. Results from this study confirm that MRI plays an important role in T-staging of rectal tumors, however, there are admittedly issues in N-staging of tumors, which should lead to reevaluation of neoadjuvant therapy indication in patients with positive lymph nodes according to MRI examination. Based on the results of this study, we see the future of preoperative staging of rectal tumors in precise T-staging together with accurate assessment of CRM and distance of tumor from mesorectal fascia as well as evaluation of intersphinteric plane and EMVI.