Retrospective study of total neoadjuvant therapy for locally advanced rectal cancer.

Aim: To compare treatment outcomes of total neoadjuvant therapy (TNT) and the standard treatment for locally advanced rectal cancer (LARC). Materials & methods: Patients with LARC (cT2-4 and/or cN1-2) who were treated with preoperative chemoradiotherapy plus induction and consolidation chemotherapy followed by surgery or the standard treatment were recruited. Pathologic complete response (pCR) rate, overall survival, disease-free survival and the sphincter preservation rate as well as safety were evaluated. Results: 49 cases were treated with TNT and 71 cases received the standard treatment. Multivariate analysis demonstrated that TNT and tumor size were independent risk factors for pCR. Grade 3 chemoradiotherapy toxicity and postoperative complications were similar between the two groups. Conclusion: TNT improved the pCR rate for patients with LARC, with tolerable toxicities.

Plain language summary Outcomes of two treatment schemes were compared for locally advanced rectal cancer (LARC), including the new preoperative treatment strategy and conventional standard preoperative chemoradiotherapy. The new preoperative treatment strategy includes the addition of four cycles of preoperative chemotherapy to the standard treatment. A total of 49 cases were treated with the new preoperative treatment strategy and 71 cases received the standard treatment. Patients treated with the new preoperative treatment demonstrated higher rates of tumor regression and organ preservation. Additionally, chemoradiotherapy-related toxicity and postoperative complications were similar between the two treatment schemes. However, neither treatment strategy prolonged the survival of patients with LARC. This new preoperative treatment strategy should be recommended first for LARC.

Feasibility and reproducibility of T2 mapping and DWI for identifying malignant lymph nodes in rectal cancer.

OBJECTIVES: To evaluate the diagnostic value and reproducibility of T2 mapping versus apparent diffusion coefficients (ADC) for identifying malignant lymph nodes in patients with non-mucinous rectal adenocarcinoma. METHODS: High-resolution magnetic resonance imaging, diffusion-weighted imaging, and T2 mapping were performed on patients with suspected metastatic lymph nodes in the mesorectum or around the superior rectal artery with a short-axis diameter of 4-10 mm. The T2 and ADC values of pathology-confirmed metastatic versus non-metastatic lymph nodes were compared using the independent-samples t test and receiver operating characteristic curves. Intra- and inter-observer reproducibility were tested. The cutoff value for T2 relaxation time was determined. RESULTS: In total, 67 lymph nodes underwent histological analysis, with 24 in the non-metastatic and 43 in the metastatic groups. Intra- and inter-observer agreements for T2 values were 0.999 and 0.998, respectively, which were higher than the ADC values of 0.924 and 0.844, respectively. The mean T2 and ADC values for metastatic lymph nodes (65 ± 7.8 ms and 1.17 ± 0.16 × 10-3 mm2/s, respectively) were significantly lower than for benign lymph nodes(83 ± 5.7 ms and 1.29 ± 0.15 × 10-3 mm2/s, respectively). T2 values had a higher AUC value of 0.990 than the AUC value for ADC of 0.729. With a cutoff value of 77 ms, sensitivity and specificity for T2 values were 95% and 96%, respectively. CONCLUSIONS: T2 mapping had higher diagnostic efficacy and reproducibility than ADC and may be useful in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. KEY POINTS: • Mean T2 values were significantly shorter for malignant versus benign LNs in patients with non-mucinous rectal adenocarcinoma. • The diagnostic efficacy and reproducibility of T2 values were excellent and superior to ADC values.

Positive peritoneal lavage fluid cytology based on isolation by size of epithelial tumor cells indicates a high risk of peritoneal metastasis.

Background: Peritoneal metastasis (PM) is the most prevalent type of metastasis in patients with gastric cancer (GC) and has an extremely poor prognosis. The detection of free cancer cells (FCCs) in the peritoneal cavity has been demonstrated to be one of the worst prognostic factors for GC. However, there is a lack of sensitive detection methods for FCCs in the peritoneal cavity. This study aimed to use a new peritoneal lavage fluid cytology examination to detect FCCs in patients with GC, and to explore its clinical significance on diagnosing of occult peritoneal metastasis (OPM) and prognosis. Methods: Peritoneal lavage fluid from 50 patients with GC was obtained and processed via the isolation by size of epithelial tumor cells (ISET) method. Immunofluorescence and fluorescence in situ hybridization (FISH) were used to identify FCCs expressing chromosome 8 (CEP8), chromosome 17 (CEP17), and epithelial cell adhesion molecule (EpCAM). Results: Using a combination of the ISET platform and immunofluorescence-FISH, the detection of FCCs was higher than that by light microscopy (24.0% vs. 2.0%). Samples were categorized into positive and negative groups, based on the expressions of CEP8, CEP17, and EpCAM. Statistically significant relationships were demonstrated between age (P = 0.029), sex (P = 0.002), lymphatic invasion (P = 0.001), pTNM stage (P = 0.001), and positivity for FCCs. After adjusting for covariates, patients with positive FCCs had lower progression-free survival than patients with negative FCCs. Conclusion: The ISET platform highly enriched nucleated cells from peritoneal lavage fluid, and indicators comprising EpCAM, CEP8, and CEP17 confirmed the diagnosis of FCCs. As a potential detection method, it offers an opportunity for early intervention of OPM and an extension of patient survival.

[Significance and expression of p53, p21(Cip1/WAF1) and Gadd45α in breast neoplasm tissues].

OBJECTIVE: To explore the expression and significance of p53, p21(Cip1/WAF1) and Gadd45α protein in breast cancer and their correlations with clinicopathologic features and prognosis in breast cancer. METHODS: The expressions of p53, p21(Cip1/WAF1) and Gadd45α proteins were determined by immunohistochemical staining. The relationship between these three proteins and clinicopathologic features in breast cancer was analyzed by χ(2) test and Spearman's rank correlation analysis. And the survival analyses were performed with the Kaplan-Meier method and Cox regression. The differences between the curves were examined with the two-tailed Log-rank test. RESULTS: In 133 cases of invasive breast cancer, the positive rates of p53, p21(Cip1/WAF1) and Gadd45α protein were 58.6%, 47.4% and 41.4% respectively. The expressions of p21(Cip1/WAF1) and p53 in cancer were significantly higher than those in the adjacent mammary gland tissue (P < 0.05) while the expression of Gadd45α was lower than that in the control mammary gland tissue (P < 0.05). The positive rate of p21(Cip1/WAF1) was correlated with the histological stage, local recurrence and positive C-erbB-2. And the positive rate of Gadd45α was correlated with the histological stage, lymph node metastasis, metastasis and positive estrogen receptor/progesterone receptor (ER/PR). The positive rate of p53 was correlated with the lymph node metastasis and TNM stage. Spearman's rank correlation analysis showed that p21(Cip1/WAF1) was correlated positively with p53, p53 negatively with Gadd45α while p21(Cip1/WAF1) had no correlation with Gadd45α. With the follow-up data, Kaplan-Meier analysis showed that p21(Cip1/WAF1), Gadd45α, p53, lymph node metastasis, C-erbB-2 positive and TMN stage were associated with prognosis. Furthermore, Cox stepwise hazard analysis shows that p21(Cip1/WAF1), Gadd45α, C-erbB-2 and TMN stage were correlated with prognosis of breast cancer. Also the Kaplan-Meier analysis showed that p53(+)Gadd45α(-) and p53(+)p21(Cip1/WAF1)(+) were correlated with a poor prognosis of breast cancer. CONCLUSIONS: The expressions of p21(Cip1/WAF1), Gadd45α and p53 are associated with the clinicopathologic features and prognosis in breast cancer. Indicating a poor prognosis of breast cancer, p53(+)Gadd45α(-) and p53(+)p21(Cip1/WAF1)(+) may become independent indices for prognostic evaluations.

A Comparison of Endoscopic Closure and Laparoscopic Repair for Gastric Wall Defection.

Objective: To compare the effectiveness and safety of endoscopic closure and laparoscopic repair for gastric wall defection. Method: The clinical data of 120 patients with submucosal tumours enrolled at our hospital between January 2014 and December 2019 were retrospectively analysed. Patients were divided into two groups according to the surgery they underwent: an endoscopic closure group (n = 60) and a laparoscopic repair group (n = 60). The clinical characteristics, perioperative complications, and postoperative follow-up results of the two groups were analysed. Results: The surgery time in the endoscopic closure group was 56.20 ± 11.25 minutes, which was significantly lower compared with that in the laparoscopic repair group (159.35 ± 23.18 minutes; P < 0.001). In addition, the postoperative stay in the endoscopic closure group was shorter than that in the laparoscopic repair group, and the intraoperative bleeding volume and incidence of enteral nutrition initiation after surgery were significantly lower. Medical expenses were also significantly lower in the endoscopic closure group than in the laparoscopic repair group (P < 0.001). Only one patient developed a postoperative fever in the endoscopic closure group; three patients developed a postoperative fever and one patient had postoperative bleeding in the laparoscopic repair group. However, there were no statistical differences between the two groups regarding the incidence of R0 resection, postoperative fever, postoperative bleeding, and closure failure (all P > 0.05). There were no local recurrences, distant metastases, or deaths in either of the groups during the two-year follow-up period. Conclusion: Non-laparoscopic-assisted surgery may be quicker, safer, and more effective for gastric wall defection.

Gut Microbiota Signatures in Tumor, Para-Cancerous, Normal Mucosa, and Feces in Colorectal Cancer Patients.

Background: Association studies have linked microbiome alterations with colorectal cancer (CRC). However, differences in tumor, para-cancerous, normal mucosal, and fecal microbiota remain to be strengthened. Methods: We performed a study on the ecologically rich and taxonomically diverse of gut microbiota using three types of colorectal mucosa (tumor mucosa, para-cancerous mucosa, normal mucosa) and feces from 98 CRC patients. Additionally, we profiled the microbiota in the fecal occult blood test (FOBT) positive and negative groups at different sampling sites. Results: We found striking variations between tumor mucosal microbiota and normal mucosal microbiota. However, there was no significant difference between tumor and para-cancerous mucosal microbiota, as well as between para-cancerous and normal mucosal microbiota, revealing that the para-cancerous mucosal microbiota was a transitional state between the tumor and normal mucosal microbiota. And the substantial shifts in the fecal microbiota compared to mucosal microbiota indicated the risk of using fecal microbiota to define mucosal microbiota. A strong correlation between FOBT positive and Fusobacterium was discovered, indicating this adherent-invasive genus was closely related to intestinal bleeding. Furthermore, we identified six key genera, including Fusobacterium, Gemella, Campylobacter, Peptostreptococcus, Alloprevotella, and Parvimonas, which appear to be consistently over-represented in tumor mucosa compared to normal mucosa and/or in mucosa compared to feces. Conclusion: Compositional alterations in the microbiota existed in three types of colorectal mucosa and feces in CRC patients. Six key genera may contribute to the topographic variances in the microbiota of tumor-bearing colorectum.

Overexpression of AMPD2 indicates poor prognosis in colorectal cancer patients via the Notch3 signaling pathway.

BACKGROUND: AMPD2 is a critical enzyme catalyzing smooth muscle energy supply and metabolism; however, its cellular biological function and clinical implication in colorectal cancer (CRC) are largely unknown. AIM: To clarify the role of AMPD2 in CRC and study the pathway and prognostic value of its role. METHODS: AMPD2 expression was analyzed by integrated bioinformatics analysis based on TCGA data sets and immunohistochemistry in tissue microarrays, and the correlation between AMPD2 expression and clinicopathological parameters, Notch3 expression, and prognostic features was assessed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then performed to investigate the regulatory pathway involved. The effects of AMPD2 expression on CRC cells and Notch3 protein expression were investigated by downregulation and overexpression of AMPD2. RESULTS: AMPD2 mRNA was significantly overexpressed in tumor tissue when compared with normal tissue in a cohort of the TCGA-COAD data set. Biological function enrichment analysis indicated that the Notch pathway strongly correlated with AMPD2 expression, and that the expression of Notch3 and JAG2 mRNA was positively associated with AMPD2 in CRC tissues. In vitro, AMPD2 overexpression markedly reduced Notch3 protein expression in CRC cells, while knockdown of AMPD2 showed the opposite findings. In addition, protein expression was significantly up-regulated in our CRC cohort as indicated by tissue microarray analysis. High expression of AMPD2 protein correlated with advanced depth of tumor and poor differentiation. Furthermore, high AMPD2 expression in CRC tissues was an indicator of poor outcome for CRC patients. CONCLUSION: AMPD2 is commonly overexpressed in CRC, and acts as a metabolism oncogene to induce CRC progression through the Notch signaling pathway. Thus, AMPD2 may be a novel prognostic biomarker for CRC.

[Application of preoperative nutritional risk screening in perioperative nutrition support for colorectal cancer patients].

OBJECTIVE: To investigate the guidance role of preoperative nutritional risk screening in perioperative nutrition support for colorectal cancer patients in order to provide evidence for the rational clinical application of nutrition support. METHODS: Nutritional risk screening was carried out in 290 hospitalized colorectal cancer patients from The Fourth People's Hospital of Wuxi City, Tongji Hospital of Tongji University and The Second Hospital of Soochow University with the nutritional risk screening(NSR) 2002 score summary table. Postoperative bowel function recovery and associated nutritional indices were compared between patients who received preoperative nutrition support according to the risk screening results and those who did not. RESULTS: Among 110 patients at nutritional risk, 65 received perioperative nutrition support and had faster recovery of intestinal function [time to first flatus (2.3±0.5) d vs. (3.3±0.5) d, time to first defecation (3.5±0.5) d vs. (4.6±0.6) d, semi-fluid intake (10.1±1.2) d vs. (12.4±2.2) d], shorter postoperative stay [(15.7±1.1) d vs. (18.8±1.4) d], and higher albumin, prealbumin and transferrin [(33.2±4.5) g/L vs. (26.0±4.0) g/L, (0.28±0.05) g/L vs. (0.16±0.04) g/L, (1.92±0.33) g/L vs. (1.75±0.45) g/L] at 7-day postoperatively (all P<0.05) as compared to those without perioperative nutrition support(n=45). While among 180 cases without nutritional risk, there were no significant differences in the above indices between patients who received preoperative nutrition support and those who did not (all P>0.05). CONCLUSION: It is important to evaluate the nutritional risk in hospitalized patients with colorectal cancer, and to carry out nutrition support actively for those at nutritional risk.