The tumor characteristics, treatment strategy, and prognosis in colorectal cancer patients with synchronous liver metastasis in China and the USA.

PURPOSE: This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA. METHODS: The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period. RESULTS: Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment (P = 0.237). CONCLUSIONS: Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade.

Prognostic Significance of D3 Lymph Node for Survival in Patients With Colorectal Cancer.

BACKGROUND: The aim of this study was to investigate the prognostic value of D3 lymph node (TSLN) for the survival of patients with colorectal cancer. METHODS: A total of 156 patients with R0 resected colorectal cancer were selected from 2011 to 2015 to carry out a retrospective study. The survival rate according to the groups of positive lymph node number (N: 1-3, N2: 4-6, N3: ≥7) and TSLN (TSLN [-], TSLN [+]) was analyzed. The influences of covariates on the 5-year overall survival (OS) and 5-year disease-free survival (DFS) were determined by the Cox proportional risk model of backward stepwise analysis. Kaplan-Meier survival analysis was used to draw survival curves between and within groups. RESULTS: During the median follow-up period (44.0 months), the 5-year DFS rate and OS rate were 45.0% and 46.0%, respectively. Survival analysis of the TSLN group showed that the 5-year OS rate and 5-year DFS rate in the TSLN (+) group (20.0 and 16.2%, respectively) were significantly lower than those in the TSLN (-) group (68.3 and 51.6%, respectively) (P < 0.001). The 5-year OS rate and DFS rate of the TSLN (+) and TSLN (-) subgroups in the N1 group were 16.7%, 33.3%, 56.7%, and 55.7%, respectively (P < 0.001). Multivariate analysis showed that positive lymph node, TSLN, and Pathological T stage were independent prognostic factors of DFS and OS for 5 years. Patients in the TSLN (+) group had a poorer prognosis. CONCLUSIONS: TSLN metastasis is an independent factor influencing the prognosis of patients, and patients with TSLN (+) have a poor prognosis. As an independent prognostic factor, this factor should be considered when evaluating the prognosis of patients.

Injectable hydrogels doped with PDA nanoparticles for photothermal bacterial inhibition and rapid wound healing in vitro.

The difficulty of wound healing due to skin defects has been a great challenge due to the complex inflammatory microenvironment. Delayed wound healing severely affects the quality of life of patients and represents a significant economic burden for public health systems worldwide. Therefore, there is an urgent need for the development of novel wound dressings that can efficiently resist drug-resistant bacteria and have superior wound repair capabilities in clinical applications. In this study, we designed an adhesive antimicrobial hydrogel dressing (GMH) based on methacrylic-anhydride-modified gelatin and oxidized hyaluronic acid formed by Schiff base and UV-induced double cross-linking for infected wound repair. By inserting PDA nanoparticles into the hydrogel (GMH/PDA), the hydrogel has the capability of photothermal conversion and exhibits good photothermal antimicrobial properties under near-infrared (NIR) light irradiation, which helps to reduce the inflammatory response and avoid bacterial infections during the wound healing process. In addition, GMH/PDA hydrogel exhibits excellent injectability, allowing the hydrogel dressings to be adapted to complex wound surfaces, making them promising candidates for wound therapy. In conclusion, the multifunctional injectable GMH/PDA hydrogel possesses high antimicrobial efficiency, antioxidant properties and good biocompatibility, making them promising candidates for the treatment of infected skin wounds.

Development of artificial blood loss and duration of excision score to evaluate surgical difficulty of total laparoscopic anterior resection in rectal cancer.

Purpose: Total laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR. Methods: RC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score. Results: A total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set. Conclusion: This preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

Development of a machine learning algorithm to predict complications of total laparoscopic anterior resection and natural orifice specimen extraction surgery in rectal cancer.

BACKGROUND: Total laparoscopic anterior resection (tLAR) and natural orifice specimen extraction surgery (NOSES) has been widely adopted in the treatment of rectal cancer (RC). However, no study has been performed to predict the short-term outcomes of tLAR using machine learning algorithms to analyze a national cohort. METHODS: Data from consecutive RC patients who underwent tLAR were collected from the China NOSES Database (CNDB). The random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), deep neural network (DNN), logistic regression (LR) and K-nearest neighbor (KNN) algorithms were used to develop risk models to predict short-term complications of tLAR. The area under the receiver operating characteristic curve (AUROC), Gini coefficient, specificity and sensitivity were calculated to assess the performance of each risk model. The selected factors from the models were evaluated by relative importance. RESULTS: A total of 4313 RC patients were identified, and 667 patients (15.5%) developed postoperative complications. The machine learning model of XGBoost showed more promising results in the prediction of complication than other models (AUROC 0.90, P < 0.001). The performance was similar when internal and external validation was used. In the XGBoost model, the top four influential factors were the distance from the lower edge of the tumor to the anus, age at diagnosis, surgical time and comorbidities. In risk stratification analysis, the rate of postoperative complications in the high-risk group was significantly higher than in the medium- and low-risk groups (P < 0.001). CONCLUSION: The machine learning model shows potential benefits in predicting the risk of complications in RC patients after tLAR. This novel approach can provide reliable individual information for surgical treatment recommendations.

An easy-to-use artificial intelligence preoperative lymph node metastasis predictor (LN-MASTER) in rectal cancer based on a privacy-preserving computing platform: multicenter retrospective cohort study.

BACKGROUND: Although the surgical treatment strategy for rectal cancer (RC) is usually based on the preoperative diagnosis of lymph node metastasis (LNM), the accurate diagnosis of LNM has been a clinical challenge. In this study, we developed machine learning (ML) models to predict the LNM status before surgery based on a privacy-preserving computing platform (PPCP) and created a web tool to help clinicians with treatment-based decision-making in RC patients. PATIENTS AND METHODS: A total of 6578 RC patients were enrolled in this study. ML models, including logistic regression, support vector machine, extreme gradient boosting (XGB), and random forest, were used to establish the prediction models. The areas under the receiver operating characteristic curves (AUCs) were calculated to compare the accuracy of the ML models with the US guidelines and clinical diagnosis of LNM. Last, model establishment and validation were performed in the PPCP without the exchange of raw data among different institutions. RESULTS: LNM was detected in 1006 (35.3%), 252 (35.3%), 581 (32.9%), and 342 (27.4%) RC patients in the training, test, and external validation sets 1 and 2, respectively. The XGB model identified the optimal model with an AUC of 0.84 [95% confidence interval (CI), 0.83-0.86] compared with the logistic regression model (AUC, 0.76; 95% CI, 0.74-0.78), random forest model (AUC, 0.82; 95% CI, 0.81-0.84), and support vector machine model (AUC, 0.79; 95% CI, 0.78-0.81). Furthermore, the XGB model showed higher accuracy than the predictive factors of the US guidelines and clinical diagnosis. The predictive XGB model was embedded in a web tool (named LN-MASTER) to predict the LNM status for RC. CONCLUSION: The proposed easy-to-use model showed good performance for LNM prediction, and the web tool can help clinicians make treatment-based decisions for patients with RC. Furthermore, PPCP enables state-of-the-art model development despite the limited local data availability.

Association Between Radiotherapy and Death From Cardiovascular Disease Among Patients With Cancer: A Large Population-Based Cohort Study.

Background This study aimed to investigate the association between radiotherapy for cancer and cardiovascular disease (CVD) deaths and evaluate the relative risk for CVD deaths in the general population and among patients with cancer treated with radiotherapy. Methods and Results The statistics of cancers from 16 sites were extracted from the Surveillance, Epidemiology, and End Results database and evaluated. Multivariable Cox proportional hazards regression analysis was used to analyze the association between radiotherapy and cardiovascular-specific survival. The standardized mortality ratio for CVD deaths was estimated by comparing the observed deaths of patients with cancer treated with radiotherapy to the expected deaths of the general population. Of the 2 214 944 patients identified from the database, 292 102 (13.19%) died from CVD. Multivariable Cox proportional hazards regression analyses demonstrated that radiotherapy was an independent risk factor for cardiovascular-specific survival among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. The long-term cardiovascular-specific survival of patients with cancer who underwent radiotherapy was significantly lower than that of patients who did not undergo radiotherapy. The incidence of CVD deaths among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers who underwent radiotherapy was higher than that among the general population. Standardized mortality ratio significantly decreased with increasing age at cancer diagnosis, gradually decreased within 10 years of diagnosis and increased after 10 years of diagnosis. Conclusions Radiotherapy is associated with worse cardiovascular-specific survival in patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. Long-term surveillance of cardiovascular conditions should be performed after radiotherapy.

Association of Radiotherapy for Rectal Cancer and Second Gynecological Malignant Neoplasms.

Importance: Radiotherapy is a common treatment for rectal cancer, yet the risk of second gynecological malignant neoplasms (SGMNs) in patients with rectal cancer undergoing radiotherapy have not been adequately studied. Objective: To investigate the association between radiotherapy and the risk of individual types of SGMN in patients with rectal cancer and assess survival outcomes. Design, Setting, and Participants: A large population-based cohort study was designed to identify the risk of SGMNs in patients with rectal cancer diagnosed from January 1973 to December 2015. The statistical analysis was conducted from September 2019 to April 2020. The study was based on the 9 cancer registries of Surveillance, Epidemiology, and End Results database. A total of 20 142 female patients with rectal cancer in localized and regional stage were included. Exposure: Receipt of neoadjuvant radiotherapy for rectal cancer. Main Outcomes and Measures: The development of an SGMN defined as any type of GMN occurring more than 5 years after the diagnosis of rectal cancer. The cumulative incidence of SGMNs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the radiotherapy-associated risk for SGMNs in patients undergoing radiotherapy vs patients not undergoing radiotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SGMNs. Results: Of 20 142 patients, 16 802 patients (83.4%) were White and the median age was 65 years (interquartile range, 54-74 years). A total of 5310 (34.3%) patients were treated with surgery and radiotherapy, and 14 832 (65.7%) patients were treated with surgery alone. The cumulative incidence of SGMNs during 30 years of follow-up was 4.53% among patients who received radiotherapy and 1.53% among patients who did not. In competing risk regression analysis, undergoing radiotherapy was associated with a higher risk of developing cancer of the uterine corpus (adjusted hazard ratio, 3.06; 95% CI, 2.14-4.37; P < .001) and ovarian cancer (adjusted hazard ratio, 2.08; 95% CI, 1.22-3.56; P = .007) compared with those who did not receive radiotherapy. The dynamic radiotherapy-associated risks (RR) for cancer of the uterine corpus significantly increased with increasing age at rectal cancer diagnosis (aged 20-49 years: adjusted RR, 0.79; 95% CI, 0.35-1.79; P = .57; aged 50-69 years: adjusted RR, 3.74; 95% CI, 2.63-5.32; P < .001; aged ≥70 years: adjusted RR, 5.13; 95% CI, 2.64-9.97; P < .001) and decreased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 3.22; 95% CI, 2.12-4.87; P < .001; 120-239 months: adjusted RR, 2.72; 95% CI, 1.75-4.24; P < .001; 240-360 months: adjusted RR, 1.95; 95% CI, 0.67-5.66; P = .22), but the dynamic RR for ovarian cancer increased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 0.70; 95% CI, 0.26-1.89; P = .48; 120-239 months: adjusted RR, 2.26; 95% CI, 1.09-4.70; P = .03; 240-360 months: adjusted RR, 11.84; 95% CI, 2.18-64.33; P = .004). The 10-year overall survival among patients with radiotherapy-associated cancer of the uterine corpus was significantly lower than that among matched patients with primary cancer of the uterine corpus (21.5% vs 33.6%; P = .01). Conclusions and Relevance: Radiotherapy for rectal cancer was associated with an increased risk of cancer of the uterine corpus and ovarian cancer. Special attention should be paid to reduce radiotherapy-associated SGMNs and improve their prognosis.

Upregulated insulin receptor tyrosine kinase substrate promotes the proliferation of colorectal cancer cells via the bFGF/AKT signaling pathway.

BACKGROUND: Some recent studies on insulin receptor tyrosine kinase substrate (IRTKS) have focused more on its functions in diseases. However, there is a lack of research on the role of IRTKS in carcinomas and its mechanism remains ambiguous. In this study, we aimed to clarify the role and mechanism of IRTKS in the carcinogenesis of colorectal cancer (CRC). METHODS: We analysed the expression of IRTKS in CRC tissues and normal tissues by researching public databases. Cancer tissues and adjacent tissues of 67 CRC patients who had undergone radical resection were collected from our center. Quantitative real-time polymerase chain reaction and immunohistochemistry were performed in 52 and 15 pairs of samples, respectively. In vitro and in vivo experiments were conducted to observe the effect of IRTKS on CRC cells. Gene Set Enrichment Analysis and Metascape platforms were used for functional annotation and enrichment analysis. We detected the protein kinase B (AKT) phosphorylation and cell viability of SW480 transfected with small interfering RNAs (siRNAs) with or without basic fibroblast growth factor (bFGF) through immunoblotting and proliferation assays. RESULTS: The expression of IRTKS in CRC tissues was higher than that in adjacent tissues and normal tissues (all P < 0.05). Disease-free survival of patients with high expression was shorter. Overexpression of IRTKS significantly increased the proliferation rate of CRC cells in vitro and the number of tumor xenografts in vivo. The phosphorylation level of AKT in CRC cells transfected with pLVX-IRTKS was higher than that in the control group. Furthermore, siRNA-IRTKS significantly decreased the proliferation rate of tumor cells and the phosphorylation level of AKT induced by bFGF. CONCLUSION: IRTKS mediated the bFGF-induced cell proliferation through the phosphorylation of AKT in CRC cells, which may contribute to tumorigenicity in vivo.

Risk and Prognosis of Secondary Rectal Cancer After Radiation Therapy for Pelvic Cancer.

BACKGROUND: The relationship between pelvic radiation therapy (RT) and second primary rectal cancer (SPRC) is unclear. The aim of this study was to assess the risk and prognosis of SPRC after pelvic RT. MATERIALS AND METHODS: Data for patients who had primary pelvic cancer (PPC) between 1973 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SPRC. Five-year overall survival (OS) and rectal cancer-specific survival (RCSS) were calculated using Kaplan-Meier curves. RESULTS: A total of 573,306 PPC patients were included, 141,225 of whom had been treated with RT. Primary cancers were located in the prostate (50.83%), bladder (24.18%), corpus uterus (16.26%), cervix (5.83%), and ovary (2.91%). A total of 1,491 patients developed SPRC. Overall, the patients who received RT were at increased risk of developing SPRC (SIR = 1.39, 95% confidence interval [CI]: 1.27-1.52). The risk of SPRC decreased in patients who did not undergo RT (SIR = 0.85, 95% CI: 0.80-0.91). The SIR for SPRC in patients who underwent external beam radiation therapy (EBRT) was 1.22 (95% CI: 1.09-1.36). The SIR for SPRC in patients who underwent a combination of EBRT and brachytherapy (EBRT-BRT) was 1.85 (95% CI: 1.60-2.14). For patients who received RT, the SIR for SPRC increased with time after a 5-year latency period from PPC diagnosis. The survival of RT-treated SPRC patients was significantly worse than that of patients with primary rectal cancer only (PRCO). CONCLUSIONS: Patients receiving pelvic RT were at an increased risk of developing SPRC. Different pelvic RT treatment modalities had different effects on the risk of SPRC. We suggest that long-term surveillance of SPRC risk is required for patients who have undergone pelvic RT, especially young patients.

Comparative short- and long-term outcomes of three techniques of natural orifice specimen extraction surgery for rectal cancer.

BACKGROUND: The aim of this study was to evaluate the safety of natural orifice specimen extraction surgery (NOSES) and to compare the short- and long-term outcomes of three techniques of NOSES for rectal cancer (RC). MATERIALS AND METHODS: A consecutive series of RC patients in stage I-III who underwent laparoscopic NOSES were enrolled. Three main techniques of NOSES included specimen eversion and extra-abdominal resection (EVER), specimen extraction and extra-abdominal resection (EXER) and intra-abdominal resection and specimen extraction (IREX). The postoperative complications, 5-year disease free survival (DFS), 5-year local recurrence rate (LRR) and 5-year distant metastasis rate (DMR) were compared in three techniques. RESULTS: 268 RC patients met inclusion criteria, including 83 patients treated with EVER, 75 patients treated with EXER and 110 patients treated with IREX. Tumor location was the most critical factor associated with technique selection, with P < 0.001. Postoperative complication rate was 12.3% for all patients, and it was 18.1% for EVER, 13.3% for EXER and 7.3% for IREX. There were no significant differences for anastomotic leakage, anastomotic bleeding and intraabdominal abscess among three technique groups, with P > 0.05. For long-term outcomes, the 5-year DFS, 5-year LRR and 5-year DMR were 85.03%, 4.22% and 11.00% for all patients. Patients in advanced tumor stage have worse long-term survival compared with patients in early stage, but no significant survival differences were observed among three technique groups. CONCLUSION: Three techniques of NOSES for RC had acceptable short- and long-term outcomes, and tumor location was a determinant of technique selection.

Risk and Prognosis of Secondary Bladder Cancer After Radiation Therapy for Rectal Cancer: A Large Population-Based Cohort Study.

BACKGROUND: Although radiation therapy (RT) improves local control for rectal cancer (RC), the long-term risks from RT, including development of a secondary malignancy, are controversial. The risk and prognosis of secondary bladder cancer (SBC) in RC patients undergoing RT have not been adequately studied. Our goal is to investigate the impact of RT on the risk of developing SBC and assess their survival outcomes. METHODS: This large population-based study included RC patients as their initial primary cancer from nine registries of the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015. The cumulative incidence of SBC was assessed by using Fine and Gray's competing risk regression. The standardized incidence ratio (SIR) was used to compare the incidence of SBC in RC survivors to the US general population. The Kaplan-Meier method was used to evaluate the 10-year overall survival (OS) and 10-year cancer specific survival (CSS) for patients with SBC. RESULTS: Of 74,646 RC patients, 24,522 patients were treated with surgery and RT and 50,124 patients were treated with surgery alone. The incidence of SBC was 1.85% among patients who received RT and 1.24% among patients who did not. The incidence of SBC in RC patients who received RT was higher than the US general population (SIR, 1.35; 95% CI, 1.19-1.53, P<0.05), and decreased with increasing age at diagnosis, and increased with time since diagnosis. In competing risk regression analysis, undergoing RT was associated with a higher risk of SBC (hazard ratio [HR], 1.443, 95% confidence interval [CI], 1.209-1.720; P<0.001). The results of the dynamic SIR for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency, and was significantly related to the variations of age at RC diagnosis and decreased with time progress. The 10-year OS and CSS among SBC patients after RT were comparable to SBC patients after NRT. CONCLUSION: Radiation was associated with an increased risk of developing SBC in RC patients, and special attention should be paid to the surveillance of these patients.

Impact of socioeconomic status on survival of colorectal cancer patients.

Socioeconomic status (SES) has an impact on the survival of various cancers, but it has not been fully understood in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was adopted to detect the role of SES in the survival outcomes of CRC. A total of 184,322 eligible patients were included and SES status was analyzed. The multivariable analysis showed that Non-Hispanic Black (HR, 1.20; 95% CI, 1.15-1.24), being widowed (HR, 1.04; 95% CI, 1.01-1.07), any Medicaid (HR, 1.36; 95% CI, 1.33-1.39) and the lowest education level group patients had relative poorer prognosis. Besides, sex, tumor location, age, differentiation level and American Joint Committee on Cancer stage also had significant effects on overall survival of CRC. The individuals were further divided into five groups according to the number of survival-adverse factors. All of the four groups containing adverse factors showed impaired survival outcomes compared with the group containing no adverse factor.