Robot-assisted radical resection of colorectal cancer using the KangDuo surgical robot versus the da Vinci Xi robotic system: short-term outcomes of a multicentre randomised controlled noninferiority trial.

BACKGROUND: The KangDuo surgical robot (KD-SR-01) was recently developed in China. This study aims to evaluate the short-term outcomes of KD-SR-01 for colorectal cancer surgery. METHODS: This is a multicentre randomised controlled noninferiority trial conducted in three centers in China. Enrolled patients were randomly assigned at a 1:1 ratio to receive surgery using the KD-SR-01 system (KD group) or the da Vinci Xi (DV) robotic system (DV group). The primary endpoint was the success rate of operation. The second endpoints were surgical outcomes, pathological outcomes, and postoperative outcomes. RESULTS: Between July 2022 and May 2023. A total of 100 patients were included in the trial and randomly assigned to the KD group (50 patients) and the DV group (50 patients). All cases were completed successfully without conversion to laparoscopic surgery. The time to flatus and the incidence of postoperative complications of Clavien-Dindo grade II or higher grade were comparable between the two groups. Surgeons reported a high level of comfort with the KD-SR-01 system. In the subgroup analysis of different operative procedures, there were no significant differences in docking time, console time, blood loss, and the length of the incision for extraction between the two groups. There were no differences in pathological outcomes including maximum tumor diameter, circumferential resection margin, distal resection margin, and number of harvested lymph nodes. CONCLUSIONS: The KD-SR-01 system was a viable option for colorectal cancer robotic surgery, with acceptable short-term outcomes comparable to the da Vinci Xi robotic system.

Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

Label-Free DNA Hybridization Detection Using a Highly Sensitive Fiber Microcavity Biosensor.

A novel label-free optical fiber biosensor, based on a microcavity fiber Mach-Zehnder interferometer, was developed and practically demonstrated for DNA detection. The biosensor was fabricated using offset splicing standard communication single-mode fibers (SMFs). The light path of the sensor was influenced by the liquid sample in the offset open cavity. In the experiment, a high sensitivity of -17,905 nm/RIU was achieved in the refractive index (RI) measurement. On this basis, the probe DNA (pDNA) was immobilized onto the sensor's surface using APTES, enabling real-time monitoring of captured complementary DNA (cDNA) samples. The experimental results demonstrate that the biosensor exhibited a high sensitivity of 0.32 nm/fM and a limit of detection of 48.9 aM. Meanwhile, the sensor has highly repeatable and specific performance. This work reports an easy-to-manufacture, ultrasensitive, and label-free DNA biosensor, which has significant potential applications in medical diagnostics, bioengineering, gene identification, environmental science, and other biological fields.

The optimal minimum lymph node count for carcinoembryonic antigen elevated colon cancer: a population-based study in the SEER set and External set.

PURPOSE: The aim of this paper was to clarify the optimal minimum number of lymph node for CEA-elevated (≥ 5 ng/ml) colon cancer patients. METHODS: Thirteen thousand two hundred thirty-nine patients from the SEER database and 238 patients from the Second Affiliated Hospital of Harbin Medical University (External set) were identified. For cancer-specific survival (CSS), Kaplan-Meier curves were drawn and data were analyzed using log-rank test. Using X-tile software, the optimal cut-off lymph node count was calculated by the maximal Chi-square value method. Cox regression model was applied to perform survival analysis. RESULTS: In CEA-elevated colon cancer, 18 nodes were defined as the optimal minimum node. The number of lymph node examined (< 12, 12-17 and ≥ 18) was an independent prognosticator in both SEER set (HR12-17 nodes = 1.329, P < 0.001; HR< 12 nodes = 1.985, P < 0.001) and External set (HR12-17 nodes = 1.774, P < 0.032; HR< 12 nodes = 2.741, P < 0.006). Moreover, the revised 18-node standard could identify more positive lymph nodes compared with the 12-node standard in this population. CONCLUSIONS: With the purpose of favorable long-term survival and accurate nodal stage for CEA-elevated colon cancer patients, the 18-node standard could be regarded as an alternative to the 12-node standard advocated by the ASCO and NCCN guidelines.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Revealing the functions of clonal driver gene mutations in patients based on evolutionary dependencies.

The clonal mutations in driver genes enable cells to gradually acquire growth advantage in tumor development. Therefore, revealing the functions of clonal driver gene mutations is important. Here, we proposed the method FCMP that considered evolutionary dependencies to analyze the functions of clonal driver gene mutations in a single patient. Applying our method to five cancer types from The Cancer Genome Atlas, we identified specific functions and common functions of clonal driver gene mutations. We found that the clonal driver gene mutations in the same patient played multiple functions. We also found that clonal mutations in the same driver gene performed different functions in different patients. These findings suggested that the clonal driver gene mutations showed strong tumor heterogeneity. In the pan-cancer analysis, the immune-related functions for clonal driver gene mutations were shared by multiple cancer types. In addition, clonal mutations in some driver genes predicted the survival of patients in cancers.

Nomogram for predicting occurrence of synchronous liver metastasis in colorectal cancer: a single-center retrospective study based on pathological factors.

PURPOSE: The purpose of this study was to explore the risk factors for synchronous liver metastasis (LM) of colorectal cancer (CRC) and to construct a nomogram for predicting the occurrence of synchronous LM based on baseline and pathological information. METHODS: The baseline and pathological information of 3190 CRC patients were enrolled in the study from the Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University between 2012 and 2020. All patients were divided into development and validation cohorts with the 1:1 ratio. The characters of LM and none-LM patients in newly diagnosed colorectal cancer were utilized to explore the risk factors for synchronous LM with the univariate and multivariate logistic regression analyses. A predictive nomogram was constructed by using an R tool. In addition, receiver operating characteristic (ROC) curves was calculated to describe the discriminability of the nomogram. A calibration curve was plotted to compare the predicted and observed results of the nomogram. Decision-making curve analysis (DCA) was used to evaluate the clinical effect of nomogram. RESULTS: The nomogram consisted of six features including tumor site, vascular invasion (VI), T stage, N stage, preoperative CEA, and CA-199 level. ROC curves for the LM nomogram indicated good discrimination in the development (AUC = 0.885, 95% CI 0.854-0.916) and validation cohort (AUC = 0.857, 95% CI 0.821-0.893). The calibration curve showed that the prediction results of the nomogram were in good agreement with the actual observation results. Moreover, the DCA curves determined the clinical application value of predictive nomogram. CONCLUSIONS: The pathologic-based nomogram could help clinicians to predict the occurrence of synchronous LM in postoperative CRC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

Long-term oncologic outcomes of natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection in the treatment of rectal cancer: a propensity-score matching study.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has been increasingly applied in radical surgery of abdominal and pelvic organs, but it is still in the exploratory stage. There is insufficient evidence to prove its efficacy. METHODS: From January 2013 to June 2017, a total of 351 patients diagnosed with rectal cancer were eventually included in this study. Patients who underwent NOSES were assigned to the NOSES group, while patients undergoing conventional laparoscopic assisted resection were assigned as to the LAP group. Propensity score matching was used to align clinicopathological features between the two groups. RESULTS: From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (47.0 ± 60.4 ml vs 87.1 ± 101.2 ml, P = 0.011), shorter postoperative gastrointestinal recovery (50.7 ± 27.3 h vs 58.6 ± 28.5 h, P = 0.040), less postoperative analgesic use (36.8% vs 52.8%, P = 0.019), lower postoperative pain scores (P < 0.001), lower rate of postoperative complications (5.7% vs 15.5%, P = 0.020), more satisfaction with body image (P = 0.001) and cosmesis (P < 0.001) postoperatively. The NOSES group had a higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between the two groups. CONCLUSION: NOSES could be a safe and reliable technique for radical resection of rectal cancer, with better short-term outcomes than conventional laparoscopy, while long-term survival is not significantly different from that of conventional laparoscopic surgery.

[Application and research of smart wearable devices for heart and brain diseases related to high altitude].

Smart wearable devices play an increasingly important role in physiological monitoring and disease prevention because they are portable, real-time, dynamic and continuous.The popularization of smart wearable devices among people under high-altitude environment would be beneficial for the prevention for heart and brain diseases related to high altitude. The current review comprehensively elucidates the effects of high-altitude environment on the heart and brain of different population and experimental subjects, the characteristics and applications of different types of wearable devices, and the limitations and challenges for their application. By emphasizing their application values, this review provides practical reference information for the prevention of high-altitude disease and the protection of life and health.

Inhibitory immune checkpoints PDCD-1 and LAG-3 hypermethylation may reduce the risk of colorectal cancer.

BACKGROUND: Changes in DNA methylation of immunosuppressive checkpoints may impact express and consequently affect antigen processing and presentation by tumor cells and facilitates evasion of immunosurveillance and lead to colorectal cancer (CRC). This study is to investigate the effect of PDCD-1, LAG-3 methylation statuses in peripheral blood leukocytes on CRC risk. METHODS: GSE51032 dataset from Gene Expression Omnibus comprised of 166 CRC patients and 424 normal samples was used to identify significantly differentially methylated CpG sites of the two genes. A case-control study with 390 CRC patients and 397 cancer-free controls was carried out to validate the relationship between the methylation levels of the two genes and CRC susceptibility and then estimated their interactions with environmental factors on CRC risk. RESULTS: In the GSE51032 dataset, cg06291111 (PDCD-1) and cg10191002 (LAG-3) were screened as the candidate CpG sites for the following study. There were significant associations between hypermethylation of PDCD-1 and LAG-3 and lower risk of CRC (ORadj = 0.322, 95% CI 0.197-0.528; ORadj = 0.666, 95% CI 0.446-0.5996, respectively). Moreover, the results in case-control study showed similar trend, that hypermethylation of PDCD-1 and LAG-3 were associated with lower CRC risk (ORadj = 0.448, 95% CI 0.322-0.622; ORadj = 0.417, 95% CI 0.301-0.578, respectively). A synergistic interaction between LAG-3 hypermethylation and intake of eggs on CRC risk was observed. There were combination effects between hypermethylation of PDCD-1 and LAG-3 and environmental factors on CRC risk. CONCLUSIONS: PDCD-1 and LAG-3 may potentially serve as blood-based predictive biomarkers for CRC risk.

A Modified Tumor-Node-Metastasis Staging System for Colon Cancer Patients with Fewer than Twelve Lymph Nodes Examined.

BACKGROUND: To construct a modified tumor-node-metastasis (TNM) staging system for stage I-III colon cancer patients with lymph nodes examined (LNE) < 12. METHODS: The clinicopathological and survival data of 3870 stage I-III colon cancer patients with LNE < 12 from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 (development cohort) and 126 stage I-III patients with LNE < 12 from the Second Affiliated Hospital of Harbin Medical University between 2011 and 2015 (validation cohort) were identified. The optimal stratification of LNR for cancer-specific survival (CSS) was achieved using X-tile software. The predictive accuracy of the modified stage (mStage) was determined by the concordance index (C-index). RESULTS: The modified N stage (mN stage) was built based on the LNR (mN0: LNR = 0, mN1: 0 < LNR < 0.4 or cancer nodule formation and mN2: 0.4 ≤ LNR ≤ 1). Preferable C-indices could be found for mStage compared with TNM stage in both development (0.750 vs 0.727) and validation cohorts (0.682 vs 0.646). Besides, patients with mStage A and B diseases could not benefit from adjuvant chemotherapy, while in patients with mStage C-F diseases, those receiving radical surgery plus adjuvant chemotherapy presented better CSS than those with radical surgery alone. CONCLUSIONS: The mStage system could predict the prognosis of colon cancer patients with LNE < 12 accurately and showed superior predictive power compared with conventional TNM staging system. Moreover, adjuvant chemotherapy might play inequable roles in patients with different mStage diseases.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Long-Term Outcome Comparison Between Two Specimen Extraction Approaches for Middle Rectum Cancer: A Retrospective Study.

Objective. There are few studies comparing the long-term results of natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic-assisted resection (LA) in the treatment of middle rectal cancer. This retrospective analysis aimed to evaluate the reliability of NOSES. Method. From January 2013 to December 2017, all patients diagnosed with median rectal cancer in our hospital who underwent NOSES and LA were enrolled. We used propensity-score matching (PSM) to balance baseline data between the NOSES group and the laparoscopic group. The primary endpoint was overall survival (OS) and disease-free survival (DFS). We used the Kaplan-Meier method to estimate OS and DFS. Student's t-test was used to analyze the difference of continuous data. Categorical data were compared using the Kruskal-Wallis test or Fisher's exact test. Results. After PSM, 38 patients were included in each group. We found that surgical bleeding volume in the NOSES group was considerably lower than that in the LA group (49.5 ± 47.5 mL vs. 86.3 ± 83.5 mL, P = .01). From the short-term results, the first flatus and regular diet time in the NOSES group were shorter than those in the LA group (41.3 ± 25.2 vs. 54.0 ± 19.2 hours, P < .01 and 63.9 ± 42.6 hours vs. 105.1 ± 66.8 hours, P < .01, respectively). Long-term OS and DFS were not different between the groups. Conclusion. Therefore, NOSES is a reliable technique for middle rectal cancer treatment. Short-term outcomes are pointedly better than LA, while the two surgical approaches did not differ in the long-term outcomes or complication rate.

Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer.

BACKGROUND: The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). METHODS: CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. RESULTS: The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). CONCLUSIONS: CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

REBACIN® as a noninvasive clinical intervention for high-risk human papillomavirus persistent infection.

The development of highly sensitive HPV-genotyping tests has opened the possibility of treating HPV-infected women before high-grade lesions appear. The lack of efficient intervention for persistent high-risk HPV infection necessitates the need for development of novel therapeutic strategy. Here we demonstrate that REBACIN®, a proprietary antiviral biologics, has shown potent efficacy in the clearance of persistent HPV infections. Two independent parallel clinical studies were investigated, which a total of 199 patients were enrolled and randomly divided into a REBACIN®-test group and a control group without treatment. The viral clearance rates for the REBACIN® groups were 61.5% (24/39) and 62.5% (35/56), respectively, for the two independent parallel studies. In contrast, the nontreatment groups showed self-clearance rates at 20.0% (8/40) and 12.5% (8/64). We further found that REBACIN® was able to significantly repress the expression of HPV E6 and E7 oncogenes in TC-1 and Hela cells. The two viral genes are well known for the development of high-grade premalignancy lesion and cervical cancer. In a mouse model, REBACIN® was indicated to notably suppress E6/E7-induced tumor growth, suggesting E6 and E7 oncogenes as a potential target of REBACIN®. Taken together, our studies shed light into the development of a novel noninvasive therapeutic intervention for clearance of persistent HPV infection with significant efficacy.

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.

A Multicenter Study Evaluating Natural Orifice Specimen Extraction Surgery for Rectal Cancer.

BACKGROUND: Low anterior resections are increasingly performed laparoscopically for rectal cancer. Recently, natural orifice specimen extraction surgery (NOSES) has been reported as an alternative approach without additional incisions or extensions. In this study, we aimed to evaluate the safety and feasibility of NOSES by comparing the short-term outcomes with those of conventional laparoscopic resection (CLR) in a multicenter retrospective study from China and Russia. METHODS: The retrospective multicenter study was conducted at three centers between January 2015 and December 2017. Relevant collected data included patient demographics, operative parameters, and postoperative complications. All procedures were performed using either a NOSES or a CLR approach. RESULTS: The data of a total of 768 consecutive patients with rectal cancer were retrospectively analyzed, including 412 CLR and 356 NOSES cases. The two groups were comparable for all demographics and characteristics except for the median tumor size (P = 0.038). No difference was found in the operative time and number of retrieved lymph nodes. Intraoperative complications and positive resection margins were nil in both groups. No difference was found in the time to first flatus (P = 0.150), time to first defecation (P = 0.084), length of postoperative hospital stay (P = 0.152), anastomotic leakage (P = 0.377), and intra-abdominal abscess (P = NA). The CLR group but not the NOSES group had incisional hernia or wound infection events, although the difference between groups was not significant (P = 0.253). CONCLUSIONS: The NOSES procedure is a well-established strategy and may be considered as an alternative procedure to CLR for rectal cancer. However, the long-term benefits of this approach require further evaluation.

NIS and epithelial-mesenchymal transition marker expression of circulating tumor cells for predicting and monitoring the radioactive iodine-131 therapy effect in differentiated thyroid cancers.

Current methods, such as serum thyroglobulin measurement and medical imaging, have limitations in the routine monitoring of the disease status and treatment response of patients with differentiated thyroid cancers (DTCs), and additional methods remain to be explored. The aim of this study was to investigate the clinical value of the sodium/iodide symporter (NIS) expression and epithelial-mesenchymal transition (EMT) phenotypes of circulating tumor cells (CTCs) in monitoring the disease status and treatment response of DTC. Blood samples were obtained from DTC patients before (1 to 3 months after total thyroidectomy) and 4 to 6 months after radioactive iodine-131 (RAI) therapy for the CTC assessments. The number, NIS expression, and EMT phenotypes of CTCs were enumerated and characterized with CanPatrol™ CTC enrichment and mRNA in situ hybridization. Postoperative NIS high expression was independently correlated with a better response to first RAI therapy and good treatment efficacy. Postoperative NIS-/epithelial-/mesenchymal+ CTCs presence was independently correlated with a worse response to first RAI therapy. The numbers of total NIS+ CTCs and NIS+/epithelial+/mesenchymal+ CTCs after first RAI therapy were negatively correlated with a better response to RAI therapy only in univariate analyses. Univariate and multivariate analyses showed that a decreased or unchanged number of total NIS+ CTCs after RAI therapy may denote good efficacy and effective RAI therapy. These preliminary data suggest that assessment of the NIS expression and EMT phenotypes of CTCs may serve as potential adjuncts for predicting and monitoring the curative effect of RAI therapy in DTC patients and avoid ineffective treatment. Further validation is warranted.

MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFß/SMAD Signaling Pathway in Colorectal Cancer Metastasis.

BACKGROUND/AIMS: Colorectal cancer (CRC) is a malignancy that has high morbidity and mortality and is initiated from accumulative genetic events. Although much effort has been made to elucidate the genetic mechanism underlying this disease, it still remains unknown. Here, we discovered a novel role for multiple epidermal growth factor-like domains protein 6 (MEGF6) in CRC, namely, that it induces the epithelial-to-mesenchymal transition (EMT) to promote CRC metastasis via the transforming growth factor beta (TGFß)/SMAD signaling pathway. METHODS: RNA sequencing data from the Gene Expression Omnibus database were analyzed using R software. Based on The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort, the clinical significance of MEGF6 was investigated. HCT8R, HCT116, and LoVo CRC cells were transfected with small interfering RNA against MEGF6, and their proliferation and sensitivity to fluorouracil were evaluated with the MTT cell proliferation and colony formation assays. Proteins associated with cell growth were detected by western blot analysis. The apoptosis of cells was evaluated by Annexin V/propidium iodide staining, and transwell assays were performed to assess the involvement of MEGF6 in cell migration. Markers of EMT and TGFß/SMAD signaling were evaluated by quantitative PCR and western blotting, and the correlation between MEGF6 and these markers was assessed in the TCGA colon and renal adenocarcinoma cohort. RESULTS: The results showed that MEGF6 was upregulated in HCT8R cells. In addition, MEGF6 was significantly overexpressed in tumor tissue and predicted a poor survival in the TCGA-COAD cohort. Moreover, MEGF6 accelerated CRC cell growth and inhibited apoptosis, and promoted CRC metastasis by inducing the EMT. Finally, we found that TGFß/SMAD signaling triggered the expression of Slug, which regulates the MEGF6-mediated EMT. CONCLUSIONS: MEGF6 may serve as an oncogene to promote cell proliferation and inhibit apoptosis. MEGF6 can also accelerate cell migration via TGFß/SMAD signaling-mediated EMT.

Reconsideration of the optimal minimum lymph node count for young colon cancer patients: a population-based study.

BACKGROUND: Currently, young colon cancer (CC) patients continue to increase and represent a heterogeneous patient group. The aim of this study was to explore the optimal minimum lymph node count after CC resection for young patients. METHODS: We performed a comprehensive search of the Surveillance, Epidemiology, and End Results (SEER) database, 2360 CC patients aged from 20 to 40 were analyzed. X-tile was used to determine the optimal cut-off point of lymph node based on survival outcomes of young patients. The cancer specific survival (CSS) was estimated with Kaplan-Meier method, the Cox proportional hazards regression model was used to analyse independent prognostic factors and exact 95% confidence intervals (CIs). RESULTS: Using X-tile analysis, 22-node measure was identified as the optimal choice for CC patients aged < 40. The 5-year CSS were 85.8% and 80.9% for patients examining ≥22 nodes and < 22 nodes. Furthermore, we identified that examining < 22 nodes was an independent adverse prognostic factor in patients aged < 40. In addition, the revised 22-node measure could examine more positive nodes than the standard 12-node measure in young patients. CONCLUSIONS: For young colon cancer patients, the lymph node examination should be differently evaluated. We suggest that 22-node measure may be more suitable for CC patients aged < 40. TRIAL REGISTRATION: Retrospectively registered.