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Objectives: Emerging evidence has demonstrated that tumour budding (TB) is negatively associated with T‐lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically 'hot' TB remain poorly understood. Methods: We quantified the number of TB by haematoxylin–eosin (H&E) sections and the densities of CD3+ and CD8+ T‐lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T‐lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB‐positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed. Results: In a CRC cohort of 351 cases, low‐grade TB was associated with high CD3+ and CD8+ T‐cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparent association with TB‐grade and T‐lymphocyte infiltration. In 278 TB‐positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low‐grade TB and positively associated with high CD3+ and CD8+ T‐cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease‐free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T‐lymphocyte infiltration. Conclusions: KRT17 can be employed as a new indicator for distinguishing different immunological TBs. [ABSTRACT FROM AUTHOR]

Functional reprogramming of tumor‐associated macrophages (TAMs) is crucial to their potent tumor‐supportive capacity. However, the molecular mechanism behind the reprogramming process remains poorly understood. Here, we identify engulfment and cell motility protein 1 (ELMO1) as a crucial player for TAM reprogramming in colorectal cancer (CRC). The expression of ELMO1 in stromal but not epithelial tumor cells was positively associated with advanced clinical stage and poor disease‐free survival in CRC. An increase in ELMO1 expression was specifically found in TAMs, but not in other multiple nonmalignant stromal cells. Gain‐ and loss‐of‐function assays indicated ELMO1 reprogrammed macrophages to a TAM‐like phenotype through Rac1 activation. In turn, ELMO1‐reprogrammed macrophages were shown to not only facilitate the malignant behaviors of CRC cells but exhibited potent phagocytosis of tumor cells. Taken together, our work underscores the importance of ELMO1 in determining functional reprogramming of TAMs and could provide new insights on potential therapeutic strategies against CRC. [ABSTRACT FROM AUTHOR]

Introduction: Since transanal total mesorectal excision (taTME) was introduced, it has become an important topic in rectal cancer treatment. Many previous studies reported positive relevant short-term results, histopathological results, and associated complications. Recently, concerns regarding the oncological safety of taTME have been raised due to reports showing high local recurrences (LR) rates. Therefore, this study aimed to compare the 3-year outcomes between taTME and laparoscopic total mesorectal excision (laTME) for mid-low rectal cancer. Methods: A total of 104 patients who underwent taTME were matched with 208 patients treated by laTME. The primary endpoint was 3-year LR rate; secondary endpoints in this matched-cohort study included the perioperative outcomes and histopathological outcomes. Results: taTME was associated with lower permanent ostomy rate (1% vs 13.5%) and lower conversion rate (0% vs 3.4%) compared to laTME. A similar quality of resected specimens was detected for each group. In both groups, the local recurrence rate was 3.8%. Within 3 years after surgery, the disease-free survival (DFS) rates were 78.8% in the taTME group and 76.9% in the laTME group (P = 0.640), while the overall survival (OS) rates were 93.3% in the taTME group and 89.9% in the laTME group (P = 0.327). Conclusion: No significant differences regarding 3-year local recurrence rate (3.8%) were observed in the taTME group compared to laTME group. [ABSTRACT FROM AUTHOR]

Background. Since Sylla and Lacy successfully reported the transanal total mesorectal excision in 2010, taTME was considered to have the potential to overcome some problematic laparoscopic cases in male, low advanced rectal cancer. However, the evidence is still lacking. This study compared the short and long outcomes of taTME with laTME in these "challenging" patients to explore the advantages of taTME among the patients. Method. After propensity score matching analysis, 106 patients were included in each group from 325 patients who met the including standard. Statistical analysis was used to compare the differences of perioperative outcomes, histopathological results, and survival results between taTME and laTME groups. Results. The mean time of pelvic operation in the taTME group was significantly shorter than in the laTME group (62.2 ± 14.2 mins vs 81.1 ± 18.9 mins, P = 0.003). The complication incidence rate and the rate of protective loop ileostomy in the taTME group were significantly lower than those in the laTME group (19.8% vs 38.7%, P = 0.003 and 70.8% vs 92.5%, P < 0.001). In long-term result, there was no significant difference between the two groups for 3-year OS (87.3% vs 85.4%, P = 0.86) or 3-year DFS (74.9% vs 70.1%, P = 0.92). The 2-year cumulative local recurrence rate was similar between the two groups (1.1% vs 5.8%, P = 0.22). Conclusion. This study demonstrated that taTME might reduce the incidence of postoperative complications, especially of anastomotic leakage in these "challenging" patients. taTME may be considered to have clear advantages for "challenging" patients. [ABSTRACT FROM AUTHOR]