From diverticulosis to complicated diverticular disease: Progression of myogenic alterations and oxidative imbalance.

BACKGROUND: The natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex-vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease. METHODS: Colonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents. KEY RESULTS: Compared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction-relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF-1 was detected in both muscle and mucosa. CONCLUSION & INFERENCES: The different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD.

Is CT Radiomics Superior to Morphological Evaluation for pN0 Characterization? A Pilot Study in Colon Cancer.

The aim of this study was to compare CT radiomics and morphological features when assessing benign lymph nodes (LNs) in colon cancer (CC). This retrospective study included 100 CC patients (test cohort) who underwent a preoperative CT examination and were diagnosed as pN0 after surgery. Regional LNs were scored with a morphological Likert scale (NODE-SCORE) and divided into two groups: low likelihood (LLM: 0-2 points) and high likelihood (HLM: 3-7 points) of malignancy. The T-test and the Mann-Whitney test were used to compare 107 radiomic features extracted from the two groups. Radiomic features were also extracted from primary lesions (PLs), and the receiver operating characteristic (ROC) was used to test a LN/PL ratio when assessing the LN's status identified with radiomics and with the NODE-SCORE. An amount of 337 LNs were divided into 167 with LLM and 170 with HLM. Radiomics showed 15/107 features, with a significant difference (p < 0.02) between the two groups. The comparison of selected features between 81 PLs and the corresponding LNs showed all significant differences (p < 0.0001). According to the LN/PL ratio, the selected features recognized a higher number of LNs than the NODE-SCORE (p < 0.001). On validation of the cohort of 20 patients (10 pN0, 10 pN2), significant ROC curves were obtained for LN/PL busyness (AUC = 0.91; 0.69-0.99; 95% C.I.; and p < 0.001) and for LN/PL dependence entropy (AUC = 0.76; 0.52-0.92; 95% C.I.; and p = 0.03). The radiomics ratio between CC and LNs is more accurate for noninvasively discriminating benign LNs compared to CT morphological features.