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Abstract Purpose This study aimed to determine the optimal natural orifice specimen extraction (NOSE) method for robotic-assisted mid-rectal cancer resection in women. Methods This retrospective propensity score-matched (PSM) study was to analyze the clinical data prospectively collected from female rectal cancer patients who underwent either robotic-assisted transvaginal specimen extraction (RATV) or robotic-assisted transanal specimen extraction (RATA) at our center between June 2016 and December 2022. The main outcome measures were urinary, anal, and sexual function. Disease-free survival (DFS), and overall survival (OS) were also included . Results Anal function, assessed by the Wexner score, was better in the RATV group than in the RATA group (P = 0.034). Additionally, pre-menopausal women in RATV group exhibited superior anal function over those in RATA group (P = 0.031). There was no statistically significant difference in urinary function between the groups for both pre-menopausal and peri-menopausal patients (P = 0.711, P = 0.106). No difference was observed in sexual function between the two groups (P = 0.351); however, pre-menopausal patients in RATA group had better sexual function than those in RATV group (P = 0.045). Univariate logistic regression analysis showed surgical procedure was not a significant factor for the occurrence of sexual dysfunction. There were no significant difference in DFS (P = 0.845)and OS (P = 0.642) between the two groups. Conclusion Though the postoperative efficacy of the RATA and RATV was equivalent on urinary and sexual function, RATV is an optimal natural orifice specimen extraction for robotic middle rectal cancer resection in women based on anal function.

Abstract Background The tumor microenvironment (TME) is a dynamic system orchestrated by intricate cell-to-cell crosstalk. Specifically, macrophages within the TME play a crucial role in driving tumor progression. Exosomes are key mediators of communication between tumor cells and the TME. However, the mechanisms underlying exosome-driven crosstalk between tumor cells and macrophages during colorectal cancer (CRC) progression remain incompletely elucidated. Methods Single-cell RNA sequencing were analyzed using the Seurat package. Exosomes were isolated using ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blot. miRNAs differentially expressed in exosomes were analyzed using the limma package. CD206 expression in CRC tissues, exosomes tracing, and exosomal miR-106a-5p transport were observed through immunofluorescence. Macrophage polarization was assessed via qRT-PCR, ELISA, and flow cytometry. The interactions between miR-106a-5p, hnRNPA1, and SOCS6 were evaluated using miRNA pull-down, RIP, and dual-luciferase reporter assays. Transwell assays and liver metastasis model explored the role of exosomal miR-106a-5p-induced M2 macrophages in promoting CRC liver metastasis. Result The proportion of M2 macrophages is increased in CRC with liver metastasis compared to those without. Highly metastatic CRC cells release exosomes enriched with miR-106a-5p, which promote macrophages M2 polarization by suppressing SOCS6 and activating JAK2/STAT3 pathway. These M2 macrophages reciprocally enhance CRC liver metastasis. hnRNPA1 regulate the transport of miR-106a-5p into exosomes. Clinically, elevated miR-106a-5p in plasma exosomes correlated with liver metastasis and poor prognosis. Conclusion CRC-derived exosomal miR-106a-5p plays a critical role in promoting liver metastasis and is a potential biomarker for the prevention and treatment of CRC liver metastasis.

BackgroundThe treatment strategy for stage II rectal mucinous adenocarcinoma (RMA) recommends neoadjuvant chemoradiotherapy (NCR) followed by total mesorectal excision (TME). However, the necessity of adjuvant chemotherapy (AC) remains controversial.Materials and methodsChi-square test was used to assess the relationship between pathological classification, AC and clinicopathological characteristics. Kaplan-Meier (KM) curves and the log-rank test were utilized to analyze differences in overall survival (OS) and cancer-specific survival (CSS) among different groups. Cox regression identified prognostic factors. Nomogram was established utilizing the independent prognostic factors. X-tile divided patients into three risk subgroups.ResultsCompared to RMA, rectal adenocarcinoma (RA) demonstrates longer OS and CSS in all and non-AC stage II patients, with no difference in OS and CSS for AC stage II patients. Propensity score matching analyses yielded similar results. Stratified analysis found that AC both improve OS of RA and RMA patients. Age, gender, pathologic T stage, regional nodes examined, and tumor size were identified as independent prognostic factors for RMA patients without AC. A nomogram was constructed to generate risk scores and categorize RMA patients into three subgroups based on these scores. KM curves revealed AC benefits for moderate and high-risk groups but not for the low-risk group. The external validation cohort yielded similar results.ConclusionsIn summary, our study suggests that, compared to stage II RA patients, stage II RMA patients benefit more from AC after NCR. AC is recommended for moderate and high-risk stage II RMA patients after NCR, whereas low-risk patients do not require AC.

Abstract Background Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. Methods Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. Results CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. Conclusion Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.

Abstract Background Robotic surgery has been widely used in the radical treatment of colonic cancer. However, it is unclear what advantages the robotic approach offers over other approaches in left colectomy. This study aims to explore the advantage of robotic surgery in left colectomy by comparing open, laparoscopic, and robotic surgery. Methods A retrospective analysis was performed on the clinical data of patients with radical left colectomy for colon cancer who were admitted to the Department of General Surgery, The First Affiliated Hospital of Nanchang University, from November 2012 to November 2017. Two hundred eleven patients included were divided into the open surgery group (OS, n=49), laparoscopic surgery group (LS, n=92), and robotic surgery group (RS, n=70) according to surgical techniques. The clinicopathologic data were collected for clinical outcome assessment. Finally, the clinical value of RS in radical left colectomy was further evaluated by propensity score matching (PSM) analysis. Results Three groups were similar in demographics and clinical characteristics. Compared with OS, LS and RS groups had better intraoperative and perioperative clinical outcomes. Moreover, the RS group exhibited the minimum operative times, length of stay (LOS), and evaluated blood loss. LS and RS also exhibited less perioperative and postoperative long-term complications. Three groups showed similar postoperative pathological outcomes. The overall survival and disease-free survival were also similar among the three groups (all P > 0.05). Cox regression analysis showed surgical approach was not a prognostic factor for overall survival (P = 0.671) and disease-free survival (P = 0.776). PSM analysis of RS and LS by clinical characteristics showed RS showed shorter operation time (P < 0.001) and LOS for patients without complications (P = 0.005). However, no significant differences were found in perioperative and long-term postoperative complications, pathological outcomes, overall survival, and disease-free survival. Conclusions Among three techniques for radical left colectomy, LS and RS had significant advantages over OS in short-term clinical outcomes, and no significant differences were found in overall, disease-free survival, local recurrence, and distant metastasis incidence. Moreover, RS shows better perioperative clinical outcomes but without compromising survival compared with LS.

Abstract Background Studies on surgical outcomes after robotic surgery are increasing; however, long-term oncological results of studies comparing robotic-assisted distal gastrectomy (RADG) versus laparoscopic-assisted distal gastrectomy (LADG) for advanced gastric cancer (AGC) are still limited. This study aimed to assess the surgical and oncological outcomes of RADG and LADG for the treatment of AGC. Methods A total of 1164 consecutive AGC patients undergoing RADG or LADG were enrolled between January 2015 and October 2021. Propensity score-matched (PSM) analysis was performed to minimize selection bias. The perioperative and oncological outcomes between the two groups were compared. Results Patient’s characteristics were comparable between the two groups after PSM. RADG group represented a longer operative time (205.2 ± 43.1 vs 185.3 ± 42.8 min, P

Abstract Background Urogenital dysfunction is recognized as a serious complication affecting patient quality of life after rectal cancer surgery to treat rectal cancer; however, the studies focus on the urogenital function after robot-assisted rectal cancer surgery compared to laparoscopic surgery are limited. Methods Male patients undergoing robotic total mesorectal excision (R-TME) or laparoscopic total mesorectal excision (L-TME) were prospectively enrolled. The International Prostate Symptom Score (IPSS) and the five-item version of the International Index of Erectile Function (IIEF-5) scale were used to compare the urogenital function of the two groups preoperatively and 3, 6, and 12 months postoperatively. Results Eighty-nine patients who planned to undergo R-TME and L-TME were prospectively enrolled; 77 patients of these patients (86.5%) completed all questionnaires at all time points and were thus included in the final analysis. Of the included patients, 38 underwent R-TME and 39 underwent L-TME. There was no significant difference in age, BMI, American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy between the two groups. Preoperative urogenital function was similar in both groups; however, the IPSS was significantly lower in R-TME patients than that in T-TME patients at 6 months and 12 months [(7.82 ± 2.25 vs. 9.95 ± 3.01, P = 0.006; 7.62 ± 2.5 vs. 9.12 ± 2.64, P = 0.012)]. IIEF-5 scores decreased 3 months after R-TME and L-TME surgery (14.87 ± 3.27 vs. 13.92 ± 3.62, p = 0.231) and then gradually increased; at 12 months, IIEF-5 scores were comparable to those at baseline in both groups. IIEF-5 scores were higher in R-TME patients than those in L-TME patients at 6 months (18.55 ± 3.45 vs. 16.75 ± 3.26, P = 0.021), but there was no significant difference between the two groups at 12 months (21.22 ± 3.06 vs. 19.95 ± 3.03, P = 0.071). Conclusions The robotic approach for TME was associated with more rapid restoration of male urogenital function than the laparoscopic approach.

BackgroundThe transvaginal route for specimen extraction is considered ideal for colorectal surgery, but its safety is still questioned. There has been little research on transvaginal natural orifice specimen extraction surgery (NOSES) in the right hemicolectomy. As a result, we conducted a study comparing transvaginal NOSES to traditional transabdominal specimen extraction surgery.Patients and methodsData on female patients who underwent radical right hemicolectomy at the First Affiliated Hospital of Nanchang University between January 2015 and December 2020 were collected retrospectively. A total of 847 patients were compliant, with 51 undergoing the transvaginal specimen extraction surgery (NOSES) group and 796 undergoing the transabdominal specimen extraction surgery (TISES) group. A propensity score matching method (1:2) was used to balance the clinicopathological characteristics of the two groups.ResultsFinally, 138 patients were enrolled in our study, with 46 in the NOSES group and 92 in the TISES group. Compared to the TISES group, the NOSES group had less intraoperative blood loss (p = 0.036), shorter time to first flatus (p < 0.001), shorter time to first liquid diet (p < 0.001), lower postoperative white blood cell counts (p = 0.026), lower C-reactive protein levels (p = 0.027), and lower visual analog scale (VAS) scores (p < 0.001). Regarding the quality of life after surgery, the NOSES group had better role function (p < 0.01), emotional function (p < 0.001), and improved symptoms of postoperative pain (p < 0.001) and diarrhea (p = 0.024). The scar satisfaction was significantly higher in the NOSES group than in the TISES group. Overall survival and disease-free survival in two groups were similar.ConclusionThe short-term results of transvaginal NOSES were superior to conventional transabdominal specimen extraction surgery. At the same time, transvaginal NOSES could improve the abdominal wall appearance and quality of life. The long-term survival was similar in the two surgical approaches. Therefore, transvaginal NOSES is worthy of our implementation and promotion.

BackgroundThe morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM.MethodsThe YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly (1488 and 639 patients, respectively). Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model’s predictive accuracy. The calibration plots were used to determine the Nomogram’s discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram’s net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software.ResultsThe Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score318) patients (P < 0.001).ConclusionA nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment.

BackgroundThe aim of the study was to develop and validate a nomogram for predicting cancer-specific survival (CSS) in lymph- node- positive rectal cancer patients after radical proctectomy.MethodsIn this study, we analyzed data collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. In addition, in a 7:3 randomized design, all patients were split into two groups (development and validation cohorts). CSS predictors were selected via univariate and multivariate Cox regressions. The nomogram was constructed by analyzing univariate and multivariate predictors. The effectiveness of this nomogram was evaluated by concordance index (C-index), calibration plots, and receiver operating characteristic (ROC) curve. Based on the total score of each patient in the development cohort in the nomogram, a risk stratification system was developed. In order to analyze the survival outcomes among different risk groups, Kaplan–Meier method was used.ResultsWe selected 4,310 lymph- node- positive rectal cancer patients after radical proctectomy, including a development cohort (70%, 3,017) and a validation cohort (30%, 1,293). The nomogram correlation C-index for the development cohort and the validation cohort was 0.702 (95% CI, 0.687–0.717) and 0.690 (95% CI, 0.665–0.715), respectively. The calibration curves for 3- and 5-year CSS showed great concordance. The 3- and 5-year areas under the curve (AUC) of ROC curves in the development cohort were 0.758 and 0.740, respectively, and 0.735 and 0.730 in the validation cohort, respectively. Following the establishment of the nomogram, we also established a risk stratification system. According to their nomogram total points, patients were divided into three risk groups. There were significant differences between the low-, intermediate-, and high-risk groups (p< 0.05).ConclusionsAs a result of our research, we developed a highly discriminatory and accurate nomogram and associated risk classification system to predict CSS in lymph-node- positive rectal cancer patients after radical proctectomy. This model can help predict the prognosis of patients with lymph- node- positive rectal cancer.

Objectives: To establish a novel risk score model that could predict the survival and immune response of patients with colon cancer.Methods: We used The Cancer Genome Atlas (TCGA) database to get mRNA expression profile data, corresponding clinical information and somatic mutation data of patients with colon cancer. Limma R software package and univariate Cox regression were performed to screen out immune-related prognostic genes. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used for gene function enrichment analysis. The risk scoring model was established by Lasso regression and multivariate Cox regression. CIBERSORT was conducted to estimate 22 types of tumor-infiltrating immune cells and immune cell functions in tumors. Correlation analysis was used to demonstrate the relationship between the risk score and immune escape potential.Results: 679 immune-related genes were selected from 7846 differentially expressed genes (DEGs). GO and KEGG analysis found that immune-related DEGs were mainly enriched in immune response, complement activation, cytokine-cytokine receptor interaction and so on. Finally, we established a 3 immune-related genes risk scoring model, which was the accurate independent predictor of overall survival (OS) in colon cancer. Correlation analysis indicated that there were significant differences in T cell exclusion potential in low-risk and high-risk groups.Conclusion: The immune-related gene risk scoring model could contribute to predicting the clinical outcome of patients with colon cancer.

Abstract Background Robotic surgery has been taken as a new modality to surpass the technical limitations of conventional surgery. Here we aim to compare the oncologic outcomes of patients with rectal cancer receiving robotic vs. laparoscopic surgery. Methods Data from patients diagnosed with rectal cancer between March 2011 and December 2018 were obtained for outcome assessment at the First Affiliated Hospital of Nanchang University. All patients were separated into two groups: a robot group (patients receiving robotic surgery, n = 314) and a laparoscopy group (patients receiving laparoscopic surgery, n = 220). The primary endpoint was survival outcomes. The secondary endpoints were the general conditions of the operation, postoperative complications and pathological characteristics. Results The 5-year overall survival (OS) and disease-free survival (DFS) at years 1, 3 and 5 were 96.6%, 88.7%, and 87.7% vs. 96.7%, 88.1%, and 78.4%, and 98.6%, 80.2-, and 73.5% vs. 96.2-, 87.2-, and 81.1% in the robot and laparoscopy groups, respectively (P > 0.05). In the multivariable-adjusted analysis, robotic surgery was not an independent prognostic factor for OS and DFS (P = 0.925 and 0.451, respectively). With respect to the general conditions of the operation, patients in the robot group had significantly shorter operation times (163.5 ± 40.9 vs. 190.5 ± 51.9 min), shorter times to 1st gas passing [2(1) vs. 3(1)d] and shorter hospital stay days [7(2) vs. 8(3)d] compared to those in the laparoscopy group (P 0.05, respectively). Conclusions This monocentre retrospective comparative cohort study revealed short-term advantages of robot-assisted rectal cancer resection but similar survival compared to conventional laparoscopy.

Abstract Objective Robotic and laparoscopic surgery for rectal cancer has been applied in the clinic for decades; nevertheless, which surgical approach has a lower rate of postoperative complications is still inconclusive. Therefore, the aim of this meta-analysis was to compare the postoperative complications within 30 days between robotic and laparoscopic rectal cancer surgery based on randomized controlled trials. Methods Randomized controlled trials (until May 2020) that compared robotic and laparoscopic rectal cancer surgery were searched through PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and China Biology Medicine disc (CBMdisc). Data regarding sample size, clinical and demographic characteristics, and postoperative complications within 30 days, including overall postoperative complications, severe postoperative complications (Clavien-Dindo score ≥ III), anastomotic leakage, surgical site infection, bleeding, ileus, urinary complications, respiratory complications, conversion to open surgery, unscheduled reoperation, perioperative mortality, and pathological outcomes, were extracted. The results were analyzed using RevMan v5.3. Results Seven randomized controlled trials that included 507 robotic and 516 laparoscopic rectal cancer surgery cases were included. Meta-analysis showed that the overall postoperative complications within 30 days [Z = 1.1, OR = 1.18, 95% CI (0.88–1.57), P = 0.27], severe postoperative complications [Z = 0.22, OR = 1.12, 95% CI (0.41–3.07), P = 0.83], anastomotic leakage [Z = 0.96, OR = 1.27, 95% CI (0.78–2.08), P = 0.34], surgical site infection [Z = 0.18, OR = 1.05, 95% CI (0.61–1.79), P = 0.86], bleeding [Z = 0.19, OR = 0.89, 95% CI (0.27–2.97), P = 0.85], ileus [Z = 1.47, OR = 0.66, 95% CI (0.38–1.15), P = 0.14], urinary complications [Z = 0.66, OR = 1.22, 95% CI (0.67–2.22), P = 0.51], respiratory complications [Z = 0.84, OR = 0.64, 95% CI (0.22–1.82), P = 0.40], conversion to open surgery [Z = 1.73, OR = 0.61, 95% CI (0.35–1.07), P = 0.08], unscheduled reoperation [Z = 0.14, OR = 0.91, 95% CI (0.26–3.20), P = 0.89], perioperative mortality [Z = 0.28, OR = 0.79, 95% CI (0.15–4.12), P = 0.78], and pathological outcomes were similar between robotic and laparoscopic rectal surgery. Conclusion Robotic surgery for rectal cancer was comparable to laparoscopic surgery with respect to postoperative complications within 30 days.

BackgroundAlthough some studies have assessed the learning curve of robotic-assisted total mesorectal excision for rectal cancer, most studies included limited sample sizes, no study used postoperative complications as an independent variable to analyze the learning curve of robotic rectal surgery, and no study evaluated the influence of the learning curve on long-term oncologic outcomes.MethodsClinical data on consecutive patients who underwent robotic-assisted total mesorectal excision for rectal cancer by a single surgeon between January 2015 and December 2018 at the First Affiliated Hospital of Nanchang University were retrospectively collected. The cumulative sum (CUSUM) and risk-adjusted cumulative sum (RA-CUSUM) were used to visualize the learning curve of operation time and postoperative complications (CD ≥ grade II). Comparisons of clinical outcomes at different learning phases analyzed by RA-CUSUM were performed after propensity score matching.ResultsA total of 389 consecutive patients were included in the analysis. The numbers of patients needed to overcome the learning curves of operation time and postoperative complications of robotic-assisted laparoscopic surgery for rectal cancer were 34 and 36, respectively. The learning process was divided into two phases based on RA-CUSUM: the learning phase (1st-36th cases) and the mastery phase (37th-389th cases). Before matching, the mastery phase had more patients with older age, lower tumor location, and neoadjuvant therapy. After matching, the two phases exhibited similar characteristics. The operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications in the mastery phase were reduced compared with the learning phase, with a median follow-up of 35 months, and the long-term oncologic outcomes were not significantly different between the two phases.ConclusionsAn experienced laparoscopic surgeon initially implements robotic-assisted total mesorectal excision for rectal cancer, surgical outcomes improved after 36 cases, and the learning curve seemingly did not have an obvious impact on long-term oncologic outcomes.

Abstract Background Colon cancer is a disease with high malignancy and incidence in the world. Tumor immune microenvironment (TIM) and tumor mutational burden (TMB) have been proved to play crucial roles in predicting clinical outcomes and therapeutic efficacy, but the correlation between them and the underlying mechanism were not completely understood in colon cancer. Methods In this study, we used Single-Sample Gene Set Enrichment Analysis (ssGSEA) and unsupervised consensus clustering analysis to divide patients from the TCGA cohort into three immune subgroups. Then we validated their differences in immune cell infiltration, overall survival outcomes, clinical phenotypes and expression levels of HLA and checkpoint genes by Mann–Whitney tests. We performed weighted correlation network analysis (WGCNA) to obtain immunity-related module and hub genes. Then we explored the underlying mechanism of hub genes by gene set enrichment analysis (GSEA) and gene set evaluation analysis (GSVA). Finally, we gave an overall view of gene variants and verified the correlation between TIM and TMB by comparing microsatellite instability (MSI) and gene mutations among three immune subgroups. Results The colon cancer patients were clustered into low immunity, median immunity and high immunity groups. The median immunity group had a favorable survival probability compared with that of the low and high immunity groups. Three groups had significant differences in immune cell infiltration, tumor stage, living state and T classification. We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration. With higher immunity, the TMB was higher. The most frequent mutations in low and median immunity groups were APC, TP53 and KRAS, while TTN and MUC16 showed higher mutational frequency in high immunity group. Conclusions We performed a comprehensive evaluation of the immune microenvironment landscape of colon cancer and demonstrated the positive correlation between immunity and TMB. The hub genes and frequently mutated genes were strongly related to immunity and may give suggestion for immunotherapy in the future.

Abstract Background Colorectal cancer resection surgery with transvaginal specimen extraction is becoming increasingly accepted and used by surgeons. However, few publications on robotic anterior sigmoid colon and rectal cancer resection with transvaginal specimen extraction (TVSE) have been reported, and a clinical outcome comparison between conventional robotic minilaparotomy (LAP) and transvaginal specimen extraction in anterior sigmoid colon and rectal cancer resection has not been performed. The current study compared the short- and long-term outcomes of TVSE and LAP for sigmoid colon cancer and rectal cancer in a mono-institution. Methods From December 2014 to October 2018, 45 patients who underwent TVSE and 45 patients who underwent LAP matched by tumor location, tumor stage, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, gender, and age at the same period were included in the current study. The short- and long-term outcomes of TVSE and LAP were discussed. Results No significant differences were found in patient characteristics. For the short-term outcomes, the operative time in the TVSE group was longer than that in the LAP group, and the postoperative pain and additional analgesia were lower in the TVSE group. Patients in the TVSE group required slightly less time to pass first flatus. There were no significant differences in overall complications, time to regular diet, length of hospital stay after surgery, estimated blood loss, or pathological outcomes. For long-term outcomes, the 3-year overall survival (94.9% vs. 91.7%, p = 0.702) and 3-year disease-free survival (88.4% vs. 86.2%, p = 0.758) were comparable between the two groups. Conclusion The robotic TVSE is safe and feasible in selected sigmoid/upper rectal cancer patients with tumor diameter < 5 cm. This approach has slightly better short-term outcomes in terms of less postoperative pain and less analgesic requirements without any significant difference in long-term outcomes.

Duodenal cavernous haemangiomas are rare, benign disorders, and massive gastrointestinal (GI) bleeding is a rare clinical condition. The present case report describes a 50-year-old male patient who presented with severe, ongoing haematochezia. A peripheral blood smear at the time of admission showed significant anaemia, and haemoglobin level was 52 g/l (normal range, 120–175 g/l). Albumin level was also low at 28 g/l (normal range, 40–55 g/l). Standard computed tomography (CT) showed mural thickening and relative lumen stenosis in the ascending (fourth) portion of the duodenum. Contrast-enhanced CT using hypotonic solution revealed the lesions to be hypervascular haemangiomas. Laparotomy and segmental duodenum resection were performed, and the first jejunal limb was anastomosed using a side-to-end technique. Histopathological examination confirmed the diagnosis of cavernous haemangioma. The patient showed marked improvement during follow-up. The present case findings emphasize that duodenal haemangioma is possible without a history of chronic anaemia, and should remain a consideration in differential diagnosis for patients presenting with massive GI bleeding. CT is useful for preoperative diagnosis of massive bleeding, and surgery with segmental resection is usually curative.

Abstract Purpose By comparing short- and long-term outcomes following totally robotic radical distal gastrectomy (TRDG) and robotic-assisted radical distal gastrectomy (RADG), we aimed to assess in which modus operandi patients will benefit more. Methods From January 2015 to May 2019, we included 332 patients undergone RADG (237) and TRDG (95). Based on the propensity score matching (PSM), inclusion and exclusion criteria, 246 patients were finally included in the propensity score-matched cohort including RADG group (164) and TRDG group (82). We then compared the short- and long-term outcomes following both groups. Results Propensity score-matched cohort revealed no significant differences in both groups. Intra-abdominal bleeding, time to pass flatus, postoperative activity time, length of incision hospital stays, and stress response were significantly less in TRDG group than in RADG group. We observed 30 complications in RADG group while 13 complications in TRDG group. There were no significant differences in TRDG group and RADG group in terms of operation time, time for anastomosis, proximal resection, distal resection margin, number of lymph node resection, and total hospitalization cost. Both 3-year overall survival and 3-year disease-free survival were comparable in both groups. Conclusions TRDG is a safe and feasible modus operandi profiting from short- and long-term outcomes compared with RADG. As surgeons improving their professional skills, TRDG could serve as the standard procedure for distal locally advanced gastric cancer with D2 lymphadenectomy.

Background Colon cancer is the third most common malignant tumor in the world. Although immunotherapy has been used in cancer treatment, there is still no first-line immunotherapy method for colon cancer. Therefore, it is essential to search for potential immunotherapy targets and molecular biomarkers for early diagnosis and prognosis. Methods In this study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) and immune-related genes from the ImmPort database. Then we filtered genes with prognostic value and constructed an immune-related signature. Patients were classified into low- and high-risk groups, and we exerted a series of analysis between the signature and clinical phenotypes. Additionally, we used protein-protein interaction networks, gene set enrichment analysis (GSEA) and single-sample gene-set enrichment analysis (ssGSEA) to explore the underlying mechanism of this signature. Furthermore, the accuracy of this signature was verified, using two data sets from Gene Expression Omnibus (GEO). Results We selected 12 immune-related genes to construct the immune-related signature. Low-risk group had a higher level of immunity compared to high-risk group. The expression level of HLA genes and checkpoint-related genes were statistically different in low- and high-risk groups. This signature showed its prognostic value in TCGA cohort and 2 GEO data sets. The signature also had strong correlation with TNM classification, stage, survival state and lymphatic invasion. The mechanism of the signature may be related to several transcription factors and CD8+ T cell in the tumor microenvironment. Conclusion In conclusion, this immune-related signature is of great prognosis value for colon cancer and its biofunction might be correlated with HLA genes, checkpoint-related genes and high-infiltrating T cells in tumor tissues.

Background Colon cancer is one of the most common tumors in the digestive tract. Studies of left-side colon cancer (LCC) and right-side colon cancer (RCC) show that these two subtypes have different prognoses, outcomes, and clinical responses to chemotherapy. Therefore, a better understanding of the importance of the clinical classifications of the anatomic subtypes of colon cancer is needed. Methods We collected colon cancer patients’ transcriptome data, clinical information, and somatic mutation data from the Cancer Genome Atlas (TCGA) database portal. The transcriptome data were taken from 390 colon cancer patients (172 LCC samples and 218 RCC samples); the somatic mutation data included 142 LCC samples and 187 RCC samples. We compared the expression and prognostic differences of LCC and RCC by conducting a multi-omics analysis of each using the clinical characteristics, immune microenvironment, transcriptomic differences, and mutation differences. The prognostic signatures was validated using the internal testing set, complete set, and external testing set (GSE39582). We also verified the independent prognostic value of the signature. Results The results of our clinical characteristic analysis showed that RCC had a significantly worse prognosis than LCC. The analysis of the immune microenvironment showed that immune infiltration was more common in RCC than LCC. The results of differential gene analysis showed that there were 360 differentially expressed genes, with 142 upregulated genes in LCC and 218 upregulated genes in RCC. The mutation frequency of RCC was generally higher than that of LCC. BRAF and KRAS gene mutations were the dominant genes mutations in RCC, and they had a strong mutual exclusion with APC, while APC gene mutation was the dominant gene mutation in LCC. This suggests that the molecular mechanisms of RCC and LCC differed. The 4-mRNA and 6-mRNA in the prognostic signatures of LCC and RCC, respectively, were highly predictive and may be used as independent prognostic factors. Conclusion The clinical classification of the anatomic subtypes of colon cancer is of great significance for early diagnosis and prognostic risk assessment. Our study provides directions for individualized treatment of left and right colon cancer.

Background Colon adenocarcinoma (COAD) is the most common colon cancer exhibiting high mortality. Due to their association with cancer progression, long noncoding RNAs (lncRNAs) are now being used as prognostic biomarkers. In the present study, we used relevant clinical information and expression profiles of lncRNAs originating from The Cancer Genome Atlas database, aiming to construct a prognostic lncRNA signature to estimate the prognosis of patients. Methods The samples were randomly spilt into training and validation cohorts. In the training cohort, prognosis-related lncRNAs were selected from differentially expressed lncRNAs using the univariate Cox analysis. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were employed for identifying prognostic lncRNAs. The prognostic signature was constructed by these lncRNAs. Results The prognostic model was able to calculate each COAD patient’s risk score and split the patients into groups of low and high risks. Compared to the low-risk group, the high-risk group had significant poor prognosis. Next, the prognostic signature was validated in the validation, as well as all cohorts. The receiver operating characteristic (ROC) curve and c-index were determined in all cohorts. Moreover, these prognostic lncRNA signatures were combined with clinicopathological risk factors to construct a nomogram for predicting the prognosis of COAD in the clinic. Finally, seven lncRNAs (CTC-273B12.10, AC009404.2, AC073283.7, RP11-167H9.4, AC007879.7, RP4-816N1.7, and RP11-400N13.2) were identified and validated by different cohorts. The Kyoto Encyclopedia of Genes and Genomes analysis of the mRNAs co-expressed with the seven prognostic lncRNAs suggested four significantly upregulated pathways, which were AGE-RAGE, focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways. Conclusion Thus, our study verified that the seven lncRNAs mentioned can be used as biomarkers to predict the prognosis of COAD patients and design personalized treatments.

BACKGROUND:The aim was to identify a novel prognostic miRNA signature for colon cancer (CC) in silico. METHODS:Data on the expression of miRNAs and relevant clinical information for 407 patients were obtained from The Cancer Genome Atlas (TCGA), and the samples were randomly split into a validation set (n = 203) and training set (n = 204). The differential expression of miRNAs between normal tissues and patients with CC was analyzed. We detected a miRNA expression signature in the training dataset by using a Cox proportional hazard regression model. Then, we verified the signature in the validation set. Association of the miRNA signature with overall survival was assessed in the validation cohort and combined cohort by log-rank test and based on Kaplan-Meier curves. The receiver operating characteristic and disease-free survival analyses were performed to evaluate the miRNA signature of CC in the combined cohort. Multivariate and univariate Cox analyses related to survival for the miRNA signature were performed, and a nomogram was built as a prognostic model for CC. To explore the function of target genes of the miRNA signature, Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used. RESULTS:Between the matched normal tissues and colon cancer tissues, 267 differentially expressed miRNAs were detected, and a single-factor CoxPH model showed that 13 miRNAs were related to overall survival in the training cohort. Then, a five-miRNA signature was identified using a CoxPH regression model with multiple factors. The five-miRNA signature had significant prognostic value in the training cohort and was validated in the validation cohort and combined cohort. A total of 193 target genes of the miRNA signature were identified. According to the results of functional analysis of the target genes, the signaling pathways MAPK, AMPK and PI3K-Akt, focal adhesion, and microRNAs in cancer were remarkably enriched. CONCLUSION:A five-miRNA signature had increased prognostic value for CC, which may provide important biological insights for the discovery and development of molecular predictors to improve the prognosis of patients with CC.

Partitioning defective 3–like protein is a novel cell polarity protein. Recently, partitioning defective 3–like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3–like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3–like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3–like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3–like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3–like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3–like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3–like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3–like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3–like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3–like protein in colorectal cancer and the feasibility of its application in clinic.

The objective of this study is to elucidate the role of Partitioning-defective 3 (Par3) in the development of gastric cancer and its correlation with different gastric cancer tissue types, particularly considering the health implications for athletes and fitness enthusiasts. From January 2019 to January 2022, 180 gastric cancer specimens, post-surgical resection, were analyzed (group B), with gastric mucosa tissue serving as a control (group A). Immunohistochemical methods assessed Par3 expression across various parameters, including tissue layer, invasion depth, tissue type, and lymph node metastasis. Key findings include a significant decrease in Par3 expression in cancer tissues compared to controls (P<0.05), no significant difference in Par3 expression between early (T1+T2) and advanced (T3+T4) stage patients (P>0.05), and similar findings regarding lymph node metastasis. Notably, Par3 expression was markedly lower in gastric type cancer than in intestinal or mixed types (P<0.05). Kappa consistency analysis indicated a significant correlation between Par3 down-regulation and gastric-type cancer (kappa=0.416), but not with other types (kappa=-0.270, -0.087). The study concludes that Par3 down-regulation is vital in gastric cancer development, particularly in gastric-type cancer, suggesting its potential as an auxiliary diagnostic marker. For athletes and fitness enthusiasts, these findings underscore the importance of monitoring gastric health, as disruptions in gastric function can significantly impact physical performance and overall well-being. [ABSTRACT FROM AUTHOR]

Abstract Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor‐specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4‐arm polyethylene glycol hydroxylamine (4‐arm PEG‐ONH2) through oxime bonds, which can be injected through a clinic‐used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.

ObjectivesTo evaluate the diagnostic accuracy of monoexponential, biexponential and stretched-exponential diffusion-weighted imaging (DWI) models in the grading of clear cell renal cell carcinoma (ccRCC).Materials and MethodsFifty-one patients with pathologically proven ccRCC underwent DWI with fifteen b factors (0, 10, 30, 50, 70, 100, 150, 200, 300, 400, 600, 800, 1000, 1500, 2000 sec/mm²) on a 3.0T MR scanner. The isotropic apparent diffusion coefficient (ADC), true diffusion coefficient (ADCslow), pseudodiffusion coefficient (ADCfast), and fraction of perfusion (f) were derived from DWI using a biexponential model. The water diffusion heterogeneity index (α) and distributed diffusion coefficient (DDC) were derived from DWI using a stretched-exponential model. All values were calculated for the solid area of tumors and compared between high-grade and low-grade ccRCC. The Mann−Whitney U test and receiver operating characteristic (ROC) analysis were used for statistical analysis. The DeLong test was performed to compare the ROC curves.ResultsThe mean ADC, DDC, ADCslow and α values were significantly lower in high-grade ccRCC than in low-grade ccRCC (P< 0.01). However, the ADCfast and f were not significantly different between the two groups (P > 0.05). According to the ROC analyses, the AUC for α was 0.941, which was significantly greater than those of the other parameters, with a sensitivity of 100% and a specificity of 84.2%. The DeLong test showed that there were significant differences in the ROCs among ADCfast/ADC, ADCfast/α, f/ADCslow, ADCfast/ADCslow, f/α, DDC/α, and f/ADC.ConclusionsDiffusion-related parameters (ADC, DDC, ADCslow and α) could be used to distinguish between low- and high-grade ccRCC. The α derived from the stretched-exponential model may be the most promising parameter for grading ccRCC.