Excessive bowel volume loss during anus-preserving surgery for rectal cancer affects the bowel function after operation: A prospective observational cohort study (Bas-1611).

Background: Bowel volume loss during anus-preserving surgery (APS) may result in low anterior resection syndrome (LARS). We conducted this prospective observational cohort study to measure the incidence of LARS after surgery and evaluate the relationship between bowel volume loss and bowel function. Methods: Patients with R0 resectable rectal cancer who consented to several bowel function surveys through telephone interviews after the operation were included. Enrolled patients underwent standard APS for rectal cancer, and three length indexes, viz. length of excised bowel, length of the distal margin and length of the proximal margin (LPM) of fresh bowel specimens, were measured in vitro. Results: The three measured variables of the specimens showed a positively skewed distribution. Patient interviews revealed a trend of gradual improvement in bowel function. Univariate analyses revealed that longer LPM was associated with a significantly negative impact on bowel function at all time points. In multivariate analysis, LPM was found to be a significant risk factorstatistically significant, but its impact was not as strong as that of radiotherapy and low-middle tumour. Furthermore, there was no significant difference in the lymph node detection rate between <10-cm and ≥10-cm LPM groups. Conclusion: In APS for rectal cancer, bowel volume loss is an important factor causing postoperative bowel dysfunction. Controlling LPM to <10 cm may help improve postoperative bowel function.

IGF2BP2 Promotes Epithelial to Mesenchymal Transition and Metastasis through Stabilizing HMGA1 mRNA in Gastric Cancer.

As an RNA-binding protein, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in enhancing the progression of a few malignant tumors by recognizing N6-methyladenosine on targeted RNA. However, the specific effects of IGF2BP2 on gastric cancer (GC) and the underlying mechanisms remain unclear. In this study, the expression level of IGF2BP2 was evaluated by analyzing data from a public database and performing immunohistochemical staining with GC specimens. The effect of IGF2BP2 on GC cell metastasis was investigated by Transwell assays and animal studies. RNA immunoprecipitation (RIP) was performed to identify potential mRNA bound to IGF2BP2. The levels of these identified RNAs were measured by RT-PCR, while corresponding proteins were quantified via Western blot. It was revealed that IGF2BP2 expression in GC tissues was significantly upregulated, and its overexpression was significantly associated with worse survival in GC patients. The aberrant expression of IGF2BP2 was demonstrated to promote the invasion and metastasis of GC cells by both in vivo and in vitro experiments. In subsequent experiments, it was then verified that by directly interacting with HMGA1 mRNA, IGF2BP2 augmented its stability and thus increased its expression. The knocking down of IGF2BP2 could significantly decrease the migration and invasion of GC cells, which could be reversed by increasing HMGA1 expression. Additionally, both in vitro and in vivo epithelial-mesenchymal transition (EMT) of GC cells were enhanced by IGF2BP2/HMGA1 axis. In conclusion, it was proven in our study that the IGF2BP2/HMGA1/EMT axis contributed to GC metastasis, suggesting its potential as a novel predictive and therapeutic biomarker for GC.

Risk Factors and Prognostic Impact of Postoperative Complications in Patients with Advanced Gastric Cancer Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy is important to improve the prognosis of patients with advanced gastric cancer. However, it may result in postoperative complications (POCs). The aim of this study is to evaluate risk factors and prognostic impact of POCs in patients receiving neoadjuvant chemotherapy. METHODS: We retrospectively collected clinical information of patients who underwent curative gastrectomy after receiving neoadjuvant chemotherapy between 2011 and 2018. Overall survival (OS) was analyzed using the Kaplan-Meier method. Logistic regression and Fisher's exact test were used to evaluate risk factors for complications. RESULTS: A total of 176 patients were included in our study. The 3-year OS rates for the complication group (n = 30) and non-complication group (n = 146) were 36.7% and 52.7%, respectively (p = 0.0294). Age, BMI, multivisceral resection and operation time were independent risk factors for POCs in patients. Patients with multivisceral resection were more likely to suffer from grade III-IV complications (p = 0.026). Inflammation complications might occur in patients with high BMI (p = 0.017). Low preoperative albumin seemed to be a risk factor for leakage complications (p = 0.033). CONCLUSIONS: Our study revealed that patients with POCs had a poor prognosis and we identified the risk factors for complications so that POCs can be avoided in time.

Down-Regulated CLDN10 Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer.

Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated. Methods: Differential expression of CLDN10 at the mRNA and protein levels was evaluated using Oncomine, ULCAN, HPA and TIMER2.0 databases. Real-time polymerase chain reaction (RT-PCR) was utilized to further verify the expression of CLDN10 in vitro. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) were performed via LinkedOmics and GeneMANIA. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number alternations (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0. Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. PPI and GSEA analysis showed that CLDN10 might be involved in signal transmission, transmembrane transport and metabolism. In some major immune cells, low expression of CLDN10 was associated with increased levels of immune cell infiltration. In addition, it was found that different SCNA status in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers. Conclusion: Down-regulated CLDN10 was associated with better overall survival (OS) in gastric cancer. And CLDN10 may serve as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.

Combination of the ratio between metastatic and harvested lymph nodes and negative lymph node count as a prognostic indicator in advanced gastric cancer: a retrospective cohort study.

BACKGROUND: The aim of our study was to examine the impact of the combination of the ratio between metastatic and harvested lymph nodes (RML) and negative lymph node (NLN) count on overall survival (OS) in patients with advanced gastric cancer (GC). METHODS: The clinicopathological data of 2,952 advanced GC patients who received curative resection between 1994 and 2015 were collected. They were divided into four groups according to the RML: 0, 0-0.1, 0.1-0.4, and >0.4. We distinguished survival differences through Kaplan-Meier analysis among the subgroups to investigate the impacts of the RML on OS in advanced GC patients. OS was examined according to clinicopathological variables. Spearman's correlation coefficient was used to assess the relationships between the RML and metastatic lymph node (MLN) count and NLN count. RESULTS: A total of 1,182 patients were enrolled into the study. The median follow-up time was 39 months (interquartile range 20 to 68 months). The 5-year OS rate of all 1,182 GC patients was 54.4%. Kaplan-Meier survival analysis showed that the median OS declined significantly with increasing RML (5-year survival rate 81.2% vs. 69.1% vs. 42.8% vs. 13.1%, P<0.001). As the NLN count increased, the survival rate of GC patients increased (5-year survival rate 12.8% vs. 25.2% vs. 60.2%, P<0.05). The RML, not NLN count, was identified as an independent factor for OS (P<0.001) through multivariate analysis. Spearman correlation analysis suggested that the RML was positively correlated with the number of MLNs (ρ=0.973, P<0.001) and inversely associated with the NLN count (ρ=-0.513, P<0.001). CONCLUSIONS: The RML is an independent prognostic predictor of OS in advanced GC patients, and the NLN count may serve as a supplementary strategy for the present tumor-node-metastasis (TNM) classification to further improve the prognostic prediction efficiency. The combination of the RML and NLN count should be an important predictor for current clinical applications.

Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer.

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer in vitro and in vivo. Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.

Texture Analysis in the Assessment of Rectal Cancer: Comparison of T2WI and Diffusion-Weighted Imaging.

Texture analysis (TA) techniques derived from T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps of rectal cancer can both achieve good diagnosis performance. This study was to compare TA from T2WI and ADC maps between different pathological T and N stages to confirm which TA analysis is better in diagnosis performance. 146 patients were enrolled in this study. Tumor TA was performed on every patient's T2WI and ADC maps, respectively; then, skewness, kurtosis, uniformity, entropy, energy, inertia, and correlation were calculated. Our results demonstrated that those significant different parameters derived from T2WI had better diagnostic performance than those from ADC maps in differentiating pT3b-4 and pN1-2 stage tumors. In particular, the energy derived from T2WI was an optimal parameter for diagnostic efficiency. High-resolution T2WI plays a key point in the local stage of rectal cancer; thus, TA derived from T2WI may be a more useful tool to aid radiologists and surgeons in selecting treatment.

Textural differences based on apparent diffusion coefficient maps for discriminating pT3 subclasses of rectal adenocarcinoma.

BACKGROUND: The accuracy of discriminating pT3a from pT3b-c rectal cancer using high-resolution magnetic resonance imaging (MRI) remains unsatisfactory, although texture analysis (TA) could improve such discrimination. AIM: To investigate the value of TA on apparent diffusion coefficient (ADC) maps in differentiating pT3a rectal adenocarcinomas from pT3b-c tumors. METHODS: This was a case-control study of 59 patients with pT3 rectal adenocarcinoma, who underwent diffusion-weighted imaging (DWI) between October 2016 and December 2018. The inclusion criteria were: (1) Proven pT3 rectal adenocarcinoma; (2) Primary MRI including high-resolution T2-weighted image (T2WI) and DWI; and (3) Availability of pathological reports for surgical specimens. The exclusion criteria were: (1) Poor image quality; (2) Preoperative chemoradiation therapy; and (3) A different pathological type. First-order (ADC values, skewness, kurtosis, and uniformity) and second-order (energy, entropy, inertia, and correlation) texture features were derived from whole-lesion ADC maps. Receiver operating characteristic curves were used to determine the diagnostic value for pT3b-c tumors. RESULTS: The final study population consisted of 59 patients (34 men and 25 women), with a median age of 66 years (range, 41-85 years). Thirty patients had pT3a, 24 had pT3b, and five had pT3c. Among the ADC first-order textural differences between pT3a and pT3b-c rectal adenocarcinomas, only skewness was significantly lower in the pT3a tumors than in pT3b-c tumors. Among the ADC second-order textural differences, energy and entropy were significantly different between pT3a and pT3b-c rectal adenocarcinomas. For differentiating pT3a rectal adenocarcinomas from pT3b-c tumors, the areas under the curves (AUCs) of skewness, energy, and entropy were 0.686, 0.657, and 0.747, respectively. Logistic regression analysis of all three features yielded a greater AUC (0.775) in differentiating pT3a rectal adenocarcinomas from pT3b-c tumors (69.0% sensitivity and 83.3% specificity). CONCLUSION: TA features derived from ADC maps might potentially differentiate pT3a rectal adenocarcinomas from pT3b-c tumors.

The prognostic impact of pretreatment anemia in patients with gastric cancer and nonhypoalbuminemia undergoing curative resection: a retrospective study.

BACKGROUND: The influence of pretreatment anemia on the prognosis of patients with advanced gastric cancer (GC) remains controversial. We retrospectively examined the impact of pretreatment anemia on the overall survival (OS) of patients with GC with nonhypoalbuminemia undergoing curative resection. METHODS: The clinicopathological data of 2,916 patients with advanced GC who received a radical gastrectomy from 1994 to 2015 were analyzed. The patients were divided into two subgroups by hemoglobin level, <120 and ≥120 g/L. OS was analyzed using the Kaplan-Meier method, and a multivariate Cox proportional hazards model was used to identify the independent prognostic factor. RESULTS: A total of 1,099 patients were included in our study. The median follow-up duration was 43 (IQR, 24-66) months. The prevalence of anemia was 40.9%. Among these 1,099 patients, 505 (46.0%) had nonhypoalbuminemia. Kaplan-Meier survival analysis showed that patients with GC who were anemic had a poorer OS than patients who were not (5-year OS rate: 58.4% vs. 66.8%, P<0.0001). Multivariate analysis revealed that pretreatment anemia was an independent prognostic factor [hazard ratio (HR) =1.455, 95% CI, 1.013-2.09; P=0.043]. CONCLUSIONS: Our findings indicate that pretreatment anemia may serve as an independent prognostic factor for patients with advanced GC with nonhypoalbuminemia after radical gastrectomy, especially those with larger tumor size and pT3 disease.

Comparison of Diagnostic Performance between Perfusion-Related Intravoxel Incoherent Motion DWI and Dynamic Contrast-Enhanced MRI in Rectal Cancer.

This study was aimed to determine the diagnostic performance of perfusion-related parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) by comparing them with quantitative parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on differentiation grades of rectal cancer. We retrospectively analyzed 98 patients with rectal cancer. Perfusion-related IVIM parameters (D ∗, f, and f·D ∗) and quantitative DCE parameters (K trans, K ep, V e , and V p ) were obtained by plotting the volume-of-interest on in-house software. Furthermore, we compared the difference and diagnostic performance of all well-moderately and poorly differentiated rectal cancer parameters. Finally, we analyzed the correlation between those DCE and IVIM parameters and pathological differentiation grade. The values of f, K trans, and K ep significantly differentiated poor and well-moderate rectal cancers. K trans achieved the highest area under the curve (AUC) value compared to perfusion-related IVIM and DCE parameters. Furthermore, K trans showed a better correlation with pathological differentiation grade than f. The diagnostic efficiency of DCE-MRI was greater than perfusion-related IVIM parameters. The f value derived from perfusion-related IVIM offered a diagnostic performance similar to DCE-MRI for patients with renal insufficiency.

Overexpression of ZNF460 predicts worse survival and promotes metastasis through JAK2/STAT3 signaling pathway in patient with colon cancer.

Zinc finger proteins (ZNFs) are a class of protein containing zinc finger domains, and they play an important role in tumor progression. However, as a member of the ZNFs family, the effect of ZNF460 in colon cancer remains unclear. In this study, we found that the expression of ZNF460 protein were markedly increased in clinical colon cancer tissues compared with para-cancer non-cancerous tissues by tissue immunohistochemistry (IHC) and western blot (WB). We also confirmed this result at the mRNA and protein levels of ZNF460 through bioinformatics analysis. In addition, high expression of ZNF460 was correlated with increased depth of invasion (P<0.05), increased lymph node metastasis (P<0.05), distant metastasis (P<0.05) and high blood serum CA19-9 level (P<0.05). High expression of ZNF460 predicted poor overall survival (OS) and recurrence free survival (RFS) in patients with colon cancer. Moreover, multivariate analyses revealed that ZNF460 was an independent prognostic factor in both OS (hazard ratio [HR]: 1.636; 95% confidence interval [CI], 1.028-2.603; P = 0.038) and RFS (HR: 2.215; 95% CI: 1.227-3.997; P = 0.008). The knockdown of ZNF460 suppressed the invasion and metastasis of colon cancer cells in vitro. Mechanistically, we revealed that ZNF460 promotes the activation of the JAK2/STAT3 signaling pathway in colon cancer cells. Taken together, overexpression of ZNF460 predicted worse survival and promoted metastasis through JAK2/STAT3 signaling pathway in patient with colon cancer, and could be a novel therapeutic target in colon cancer.

Correction: A Novel Remote Follow-Up Tool Based on an Instant Messaging/Social Media App for the Management of Patients With Low Anterior Resection Syndrome: Pilot Prospective Self-Control Study.

[This corrects the article DOI: 10.2196/22647.].

A Novel Remote Follow-Up Tool Based on an Instant Messaging/Social Media App for the Management of Patients With Low Anterior Resection Syndrome: Pilot Prospective Self-Control Study.

BACKGROUND: Low anterior resection syndrome (LARS) is a common functional disorder that develops after patients with rectal cancer undergo anal preservation surgery. Common approaches to assess the symptoms of patients with LARS are often complex and time-consuming. Instant messaging/social media has great application potential in LARS follow-up, but has been underdeveloped. OBJECTIVE: The aim of this study was to compare data between a novel instant messaging/social media follow-up system and a telephone interview in patients with LARS and to analyze the consistency of the instant messaging/social media platform. METHODS: Patients with R0 resectable rectal cancer who accepted several defecation function visits via the instant messaging/social media platform and agreed to a telephone interview after the operation using the same questionnaire including subjective questions and LARS scores were included. Differences between the 2 methods were analyzed in pairs and the diagnostic consistency of instant messaging/social media was calculated based on telephone interview results. RESULTS: In total, 21 questionnaires from 15 patients were included. The positive rates of defecation dissatisfaction, life restriction, and medication use were 10/21 (48%), 11/21 (52%), and 8/21 (38%) for telephone interview and 10/21 (48%), 13/21 (62%), and 5/21 (24%) for instant messaging/social media, respectively. No statistically significant difference was observed between instant messaging/social media and telephone interview in terms of total LARS score (mean 22.4 [SD 11.9] vs mean 24.7 [SD 10.7], P<.21) and LARS categories (Z=-0.264, P=.79); however, instant messaging/social media showed a more negative tendency. The kappa values of 3 subjective questions were 0.618, 0.430, and 0.674, respectively. The total LARS scores were consistent between both groups (Pearson coefficient 0.760, P<.001; category correlation coefficient 0.570, P=.005). Patients with major LARS had highly consistent results, with sensitivity, specificity, kappa value, and P value of 77.8%, 91.7%, 0.704, and .001, respectively. CONCLUSIONS: Instant messaging/social media can be a major LARS screening method. However, further research on information accuracy and user acceptance is needed before implementing a mature system. TRIAL REGISTRATION: ClinicalTrials.gov NCT03009747; https://clinicaltrials.gov/ct2/show/NCT03009747.

Prediction of Clinical Pathologic Prognostic Factors for Rectal Adenocarcinoma: Volumetric Texture Analysis Based on Apparent Diffusion Coefficient Maps.

Texture analysis has been used to characterize and measure tissue heterogeneity in medical images. The purpose of this study was to investigate the potential of texture features derived from apparent diffusion coefficient (ADC) maps, to serve as imaging markers for predicting important histopathologic prognostic factors in rectal cancer. One hundred patients of rectal cancer received 3 T preoperative magnetic resonance imaging including diffusion-weighted imaging (DWI). Skewness, kurtosis, uniformity from the histogram and entropy, energy, inertia, correlation from gray-level co-occurrence matrix (GLCM) derived from whole-lesion volumes were measured. Independent sample t-test or Mann-Whitney U-test and receiver operating characteristic (ROC) curves were used for statistical analysis. Uniformity, energy and entropy were significantly different (p = 0.026, 0.001, and 0.006, respectively) between stage pT1-2 and pT3-4 tumors. Skewness, kurtosis and correlation were significantly different (p = 0.000, 0.006, and 0.041, respectively) between grade 1-2 and grade 3 tumors. Energy and entropy (p = 0.008 and 0.033, respectively) could significantly differentiate negative circumferential resection margin (CRM) from positive CRM. Furthermore, predicted probabilities derived by logistic regression analysis yielded greater area under the curve (AUC) in differentiating pT3-4 stage and grade 3 grade tumors. Texture features derived from ADC maps may useful to predict important histopathologic prognostic factors of rectal cancer.

Therapeutic potential of ADAM17 modulation in gastric cancer through regulation of the EGFR and TNF-α signalling pathways.

A disintegrin and metalloproteinase 17 (ADAM17) is highly expressed in various tumours and affects tumour progression. In this study, ADAM17 expression in 60 gastric cancer and 20 normal gastric mucosal tissues was assessed using immunohistochemistry. ADAM17 expression was higher in gastric cancer tissues than in normal gastric mucosal tissues (P < 0.0005). A significant relationship was identified between ADAM17 expression and the depth of tumour invasion, metastasis, and carcinoma stage. Furthermore, the effects of ADAM17 knockdown on the proliferation, cell invasion, and apoptosis of human gastric carcinoma cells (SGC-7901) were determined. SGC-7901 cells were transfected with ADAM17-shRNA, and cell proliferation and migration were assessed using CCK-8 and transwell assays, respectively, to evaluate the role of ADAM17 in tumour proliferation and invasion. Furthermore, the EGFR signalling pathway, the cell membrane receptor-bound TNF-α level, and apoptosis were evaluated by western blotting and flow cytometry. The inhibition of cell proliferation and invasion was observed in the ADAM17 knockdown cells, which was associated with modulation of the EGFR signalling pathway. Apoptosis was increased, and TNF-α signalling was attenuated in the ADAM17 knockdown cells. Our study demonstrated that ADAM17 over-expression in gastric cancer tissues was closely associated with tumour proliferation, invasion, and apoptosis.