[Analysis of clinicopathological features and prognosis of sporadic synchronous multiple primary colorectal cancers].

Objective: To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis. Methods: The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result: Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III-IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ2=6.293,P=0.043). The proportions of TNM Stage III-IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ2=13.994,P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ2=10.457,P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ2=5.086,P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ2=19.791,P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ2=4.601,P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ2=11.996,P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ2=7.643, P=0.006), had a higher proportion of TNM Stage III-IV disease (60.2% [100/166] vs. 24.2% [8/33], χ2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively (P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS (P=0.026). Conclusions: Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system.

Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-ß1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-ß1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.