Background: Neuroendocrine differentiation (NED) is often found in colorectal cancer (CRC) and may have unique biological behavior, which has not been previously delineated. Here, we explore the relationship between CRC, NED, and clinicopathological factors. We also offer a preliminary explanation of the mechanism underlying the malignant biological behavior of NED in CRC. Methods: Between 2013 and 2015, 394 CRC patients who underwent radical operations were selected for analysis. The relationship between NED and clinicopathological factors was analyzed. To further clarify the pivotal role of NED in CRC, we performed bioinformatic analyses and identified genes that may be involved in NED, which were obtained from in silico data from The Cancer Genome Atlas (TCGA) database. Then, we conducted functional enrichment analyses and confirmed the critical pathways for intensive study. Moreover, we detected the expression of key proteins by immunohistochemistry and analyzed the correlation of their expression with NED. Results: The statistical analysis showed that CRC with NED was positively correlated with lymph node metastasis. Through bioinformatic analysis, we found that chromogranin A (CgA) was positively correlated with invasion and lymph node metastasis. ErbB2 and PIK3R1, which are key proteins in the PI3K-Akt signaling pathway, were closely related to NED. Furthermore, we determined that the PI3K-Akt signaling pathway likely plays a critical role in the NED of CRC. Conclusions: CRC with NED is associated with lymph node metastasis. The PI3K-Akt signaling pathway, which is closely related to CRC, may be the mechanism promoting the malignant biological behavior of CRC with NED.

Background: In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described. Methods: This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis. Results: Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133–42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811–4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015–3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728–2.806, P = 0.294). Conclusions: We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

Objective: The objectives of this study were to analyze the difference between the preoperative radiological and postoperative pathological stages of colorectal cancer (CRC) and explore the feasibility of elastic lamina invasion (ELI) as a prognostic marker for patients with stage III colon cancer. Methods: A total of 105 consecutive patients underwent radical surgery (R0 resection) for stage III colon cancer at the Cancer Hospital of China Medical University between January 2015 and December 2017. Clinicopathological features, including radiological stage and elastic lamina staining, were analyzed for prognostic significance in stage III colon cancer. Results: A total of 105 patients with stage III colon cancer who met the criteria and had complete data available were included. The median follow-up period of survivors was 41 months. During the follow-up period, 33 (31.4%) patients experienced recurrence after radical resection, and the 3-year disease-free survival (DFS) rate was 64.8%. The consistency between preoperative radiological and postoperative pathological staging was poor (κ = 0.232, P < 0.001). The accuracy of ≤ T2 stage diagnoses was 97.1% (102/105), that of T3 stage was 60.9% (64/105), that of T4a stage was 68.6% (72/105) and that of T4b stage was 91.4% (96/105). The DFS rate of T3 ELI (+) patients was significantly lower than that of both T3 ELI (−) patients (P = 0.000) and pT4a patients (P = 0.013). The DFS rate of T3 ELI (−) patients was significantly higher than that of pT4b patients (P=0.018). T3 ELI (+) (HR (Hazard ratio), 8.444 [95% CI, 1.736–41.067]; P = 0.008), T4b (HR, 57.727[95% CI, 5.547-600.754]; P = 0.001), N2 stage (HR, 10.629 [95% CI, 3.858–29.286]; P < 0.001), stage III (HR, 0.136 [95% CI, 0.31–0.589]; P = 0.008) and perineural invasion (PNI) (HR, 8.393 [95% CI, 2.094–33.637]; P = 0.003) were independent risk factors for postoperative recurrence of stage III colon cancer. Conclusions: The consistency between preoperative radiological and postoperative pathological staging was poor, especially for tumors located in the ascending colon and descending colon. Elastic lamina staining is expected to become a stratified indicator of recurrence risk for patients with stage III colon cancer and a guide for individualized adjuvant chemotherapy, thus improving patient prognosis.

Our previous study demonstrated that the linear quadratic model appeared to be not well-suited for high dose per fraction due to an observed increase in α/β ratio as the dose per fraction increased. To further validate this conclusion, we draw the cell survival curve to calculate the α/β ratio by the clone formation experiment and then convert the fractionated radiation dose into an equivalent single hypofractionated radiation dose comparing with that on the survival curve. Western Blot and laser confocal immunofluorescence were used to detect the expression of γ-H2AX and RAD51 after different fractionated modes of radiation. We constructed a murine xenograft model, and changes in transplanted tumor volume were used to evaluate the biological effects after different fractionated radiation. The results demonstrated that when fractionated radiation dose was converted into equivalent single hypofractionated radiation dose, the effectiveness of hypofractionated radiation was overestimated. If a larger α/β ratio was used, the discrepancy tended to become smaller. γ-H2AX was higher in 24 h after a single high dose radiation than the continuous expression of the DNA repair marker RAD51. This implies more irreparable damage in a single high dose radiation compared with fractionated radiation. In the murine xenograft model, the effectiveness of hypofractionated radiation was also overestimated, and additional fractions of irradiation may be required. The conclusion is that after single hypofractionated radiation, the irreparable damage in cells increased (α value increased) and some repairable sublethal damage (β value) was converted into irreparable damage (α value). When α value increased and β value decreased, the ratio increased.

Esophageal squamous cell carcinoma (ESCC) is commonly associated with high rates of malnutrition, adversely affecting patient outcomes. This study aims to assess the impact of nutritional support combined with concurrent chemoradiotherapy (CCRT) on survival and prognosis in ESCC patients, utilizing prognostic models based on five key immunonutritional indicators. In this retrospective study, we reviewed the medical records of 200 esophageal squamous cell carcinoma patients who were treated between January 2017 and June 2022. Patients were categorized into two groups based on their treatment records: one group received nutritional support in addition to standard CCRT, and the other received only CCRT. We retrospectively analyzed survival outcomes using Kaplan-Meier curves and log-rank tests, and identified independent prognostic factors through Cox proportional hazards models. The study further assessed five specific immunonutritional indicators to develop and validate predictive nomogram models. The effectiveness of these models was evaluated using receiver operating characteristic (ROC) curve analysis to determine their predictive accuracy for patient outcomes. Nutritional support improved overall survival (OS) and progression-free survival (PFS) compared to the non-nutritional group. Patients in the nutritional group showed better biochemical markers and quality of life with fewer treatment-related complications. The nomogram models based on the immunonutritional indicators demonstrated strong predictive accuracy for both OS and PFS, with LMY and PAR showing the highest prognostic power. Integrating nutritional support into the treatment plan for ESCC patients undergoing CCRT enhances may enhance treatment tolerance, reduce toxicity, and indirectly contribute to improved survival rates, quality of life, and fewer complications. The five immunonutritional indicators provide robust predictive capabilities for patient outcomes, supporting the use of personalized nutritional interventions and nomogram models in clinical practice.