Impact of lymph node retrieval on prognosis in elderly and non-elderly patients with T3-4/N+ rectal cancer following neoadjuvant therapy: a retrospective cohort study.

PURPOSE: The optimal number of lymph nodes to be resected in patients with rectal cancer who undergo radical surgery after neoadjuvant therapy remains controversial. This study evaluated the prognostic variances between elderly and non-elderly patients and determined the ideal number of lymph nodes to be removed in these patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) datasets were used to gather information on 7894 patients diagnosed with stage T3-4/N+ rectal cancer who underwent neoadjuvant therapy from 2010 to 2019. Of these patients, 2787 were elderly and 5107 were non-elderly. A total of 152 patients from the Longyan First Affiliated Hospital of Fujian Medical University were used for external validation. Overall survival (OS) and cancer-specific survival (CSS) were evaluated to determine the optimal quantity of lymph nodes for surgical resection. RESULTS: The study found significant differences in OS and CSS between elderly and non-elderly patients, both before and after adjustment for confounders (P < 0.001). The removal of 14 lymph nodes may be considered a benchmark for patients with stage T3-4/N+ rectal cancer who undergo radical surgery following neoadjuvant therapy, as this number provides a more accurate foundation for the personalized treatment of rectal cancer. External data validated the differences in OS and CSS and supported the 14 lymph nodes as a new benchmark in these patients. CONCLUSION: For patients with T3-4/N+ stage rectal cancer who undergo radical surgery following neoadjuvant therapy, the removal of 14 lymph nodes serves as a cutoff point that distinctly separates patients with a favorable prognosis from those with an unfavorable one.

Predicting treatment failure in stage III colon cancer patients after radical surgery.

Purpose: The aim to assess treatment failure in patients with stage III colon cancer who underwent radical surgery and was analyzed using the nomogram. Methods: Clinical factors and survival outcomes for stage III colon cancer patients registered in the SEER database from 2018 to 2019 were analyzed, with patients split into training and testing cohorts (7:3 ratio). A total of 360 patients from the First Affiliated Hospital of Longyan served as an external validation cohort. Independent predictors of treatment failure were identified using logistic regression analyses. The nomograms was evaluated by concordance index (C-index), calibration curves, and the area under the curve (AUC), decision curve analysis (DCA) and clinical impact curves (CIC) assessed the clinical utility of nomograms versus TNM staging. Results: The study included 4,115 patients with stage III colon cancer. Multivariate logistic analysis age, tumor site, pT stage, pN stage, chemotherapy, pretreatment CEA levels, number of harvested lymph nodes, perineural invasion and marital status were identified as independent risk factors for treatment failure. The C-indices for the training and testing sets were 0.853 and 0.841. Validation by ROC and calibration curves confirmed the stability and reliability of the model. DCA showed that the net clinical effect of the histogram was superior to that of the TNM staging system, while CIC highlighted the potentially large clinical impact of the model. Conclusions: The developed Nomogram provides a powerful and accurate tool for clinicians to assess the risk of treatment failure after radical surgery in patients with stage III colon cancer.

Conditional survival analysis and real-time prognosis prediction in stage III T3-T4 colon cancer patients after surgical resection: a SEER database analysis.

BACKGROUND: Conditional survival (CS) takes into consideration the duration of survival post-surgery and can provide valuable additional insights. The aim of this study was to investigate the risk factors associated with reduced one-year postoperative conditional survival in patients diagnosed with stage III T3-T4 colon cancer and real-time prognosis prediction. Furthermore, we aim to develop pertinent nomograms and predictive models. METHODS: Clinical data and survival outcomes of patients diagnosed with stage III T3-T4 colon cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2010 to 2019. Patients were divided into training and validation cohorts at a ratio of 7:3. The training set consisted of a total of 11,386 patients for conditional overall survival (cOS) and 11,800 patients for conditional cancer-specific survival (cCSS), while the validation set comprised 4876 patients for cOS and 5055 patients for cCSS. Univariate and multivariate Cox regression analyses were employed to identify independent risk factors influencing one-year postoperative cOS and cCSS. Subsequently, predictive nomograms for cOS and cCSS at 2-year, 3-year, 4-year, and 5-year intervals were constructed based on the identified prognostic factors. The performance of these nomograms was rigorously assessed through metrics including the concordance index (C-index), calibration curves, and the area under curve (AUC) derived from the receiver operating characteristic (ROC) analysis. Clinical utility was further evaluated using decision curve analysis (DCA). RESULTS: A total of 18,190 patients diagnosed with stage III T3-T4 colon cancer were included in this study. Independent risk factors for one-year postoperative cOS and cCSS included age, pT stage, pN stage, pretreatment carcinoembryonic antigen (CEA) levels, receipt of chemotherapy, perineural invasion (PNI), presence of tumor deposits, the number of harvested lymph nodes, and marital status. Sex and tumor site were significantly associated with one-year postoperative cOS, while radiation therapy was notably associated with one-year postoperative cCSS. In the training cohort, the developed nomogram demonstrated a C-index of 0.701 (95% CI, 0.711-0.691) for predicting one-year postoperative cOS and 0.701 (95% CI, 0.713-0.689) for one-year postoperative cCSS. Following validation, the C-index remained robust at 0.707 (95% CI, 0.721-0.693) for one-year postoperative cOS and 0.700 (95% CI, 0.716-0.684) for one-year postoperative cCSS. ROC and calibration curves provided evidence of the model's stability and reliability. Furthermore, DCA underscored the nomogram's superior clinical utility. CONCLUSIONS: Our study developed nomograms and predictive models for postoperative stage III survival in T3-T4 colon cancer with the aim of accurately estimating conditional survival. Survival bias in our analyses may lead to overestimation of survival outcomes, which may limit the applicability of our findings.

Comparing the short-term clinical outcomes and therapeutic effects of different colectomies in patients with refractory slow-transit constipation in eastern countries: a network meta-analysis.

Surgical treatment has been widely used in patients with refractory slow transit constipation (RSTC). The aim of this network meta-analysis (NMA) was to compare the effects of different colectomies on short-term postoperative complications and quality of life in patients with RSTC. Electronic literature searches were performed in the PubMed, Web of Science, EMBASE, WANFANG DATA, and Cochrane Central Register of controlled trials databases and were searched up to December 2022. Selected to compare the short-term clinical outcomes and quality of life of the treatment of RSTC. A random-effects Bayesian NMA was conducted to assess and rank the effectiveness of different surgical modalities. This study included a total of six non-randomized controlled trials involving 336 subjects. It was found that subtotal colectomy with cecorectal anastomosis (CRA) demonstrated superior effectiveness in several aspects, including reduced hospital stay (MD 0.06; 95% CI [0.02, 1.96]), shorter operative time (MD 4.75; 95% CI [0.28, 14.07]), lower constipation index (MD 0.61; 95% CI [0.04, 1.71]), improved quality of life (MD 4.42; 95% CI [0.48, 4.42]). Additionally, in terms of short-term clinical outcomes, subtotal colectomy with ileosigmoidal anastomosis (SC-ISA) procedure ranked the highest in reducing small bowel obstruction (OR 0.24; 95% CI [0.02, 0.49]), alleviating abdominal pain (OR 0.53; 95% CI [0.05, 1.14]), minimizing abdominal distension (OR 0.33; 95% CI [0.02, 0.65]), and reducing incision infection rates (OR 0.17; 95% CI [0.01, 0.33]). Furthermore, SC-ISA ranked as the best approach in terms of patient satisfaction (OR 0.66; 95% CI [0.02, 1.46]). Based on our research findings, we recommend that CRA be considered as the preferred treatment approach for patients diagnosed with RSTC.

Association of hemicolectomy with survival in stage II colorectal cancer: a retrospective cohort study.

To compare the oncological survival outcomes of partial colectomy (PC) and hemicolectomy (HC) in patients with stage II colon cancer. A total of 18,795 patients with stage II colon cancer who underwent hemicolectomy (n = 12,022) or partial colectomy (n = 6773) from 2010 to 2019 were included in the the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were compared between the two groups, and the threshold of harvested lymph nodes was determined. The results showed that age, gender, race, tumor site, scope of regional lymph nodes, postoperative chemotherapy, postoperative radiotherapy, harvested lymph nodes, and tumor size were significantly different between the PC and HC groups (all P < 0.05). The OS rate was slightly lower in hemicolectomy patients than in partial colectomy patients (69.9% vs. 74.5%, respectively, P < 0.001), but CSS was similar between the two groups (87.9% vs. 88.1%, respectively, P = 0.32). After propensity score matching (PSM) was performed, the OS and CSS rates in the two groups were significantly different (CSS 84.3% vs. 88.0%, P < 0.001; OS 62.2% vs. 72.5%, P < 0.001). The survminer R package determined that the optimum threshold for the harvested lymph node count in stage II colon cancer patients was 16. CSS was significantly different between patients with ≥ 12 lymph nodes harvested and patients with ≥ 16 lymph nodes harvested (P = 0.043). Univariate and multivariate Cox regression and survival analyses of stage II colon cancer patients showed that the survival benefit of stage II colon cancer patients receiving partial colectomy was superior to that of patients receiving hemicolectomy. Partial colectomy has significant oncological benefits over hemicolectomy in the treatment of stage II colon cancer patients, even in the case of pT4b or tumor deposits. Removal of 16 lymph nodes during colectomy for stage II colon cancer correlated with improved survival, and this threshold was more effective than the standard threshold of 12 lymph nodes in distinguishing between patients with good and poor prognoses.

Comparison of the short-term and long-term outcomes of three different types of inferior mesenteric artery ligation in left colonic and rectal cancers: a network meta-analysis.

To perform a network meta-analysis of the literature to assess the short-term and long-term outcomes of three operations for left colon and rectal cancer. Electronic literature searches were performed in the PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials databases up to August 2022. A Bayesian network meta-analysis using R software, ADDIS, and Review Manager 5.4 was conducted to compare outcomes of high ligation of the inferior mesenteric artery(IMA),low ligation of the IMA with D2 dissection (LLD2), and low ligation of the IMA with D3 dissection (LLD3). Sensitivity analysis was applied to investigate the influence of each primary study on the final result of the meta-analysis. Asymmetry of data was estimated by using Egger's tests. Publication bias corrected by trimming and filling method. A total of 44 studies, 5 randomized clinical trials (RCTs) and 39 non-RCTs, were included in this meta-analysis. HL was associated with a higher risk of anastomotic leakage (HL vs. LLD2, OR = 1.35, 95% CI 1.13-3.25, P = 0.001; HL vs. LLD3, OR = 1.65, 95% CI 1.35-2.01, P < 0.001), and required a longer postoperative hospital stay (HL vs. LLD3, SMD = 0.28, 95%CI 0.09-0.48, P = 0.01).However HL showed an advantage in terms of operation time(HL vs. LLD3, SMD = - 0.13, 95%CI - 0.26 to 0.01, P = 0.04). LLD3 is most likely to rank best in terms of short-term and long-term outcomes after surgery for left colon and rectal cancer. Caution should be taken in the risk of anastomotic leakage when treating colorectal cancer with LLD2. HL, LLD2 and LLD3 provide similar overall survival rates for left colon and rectal cancer.

Long-term prognostic benefit of adjuvant chemotherapy for patients with hepatoid adenocarcinoma of the stomach after radical resection: A national multicenter study.

BACKGROUND: There is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. METHODS: The clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). RESULTS: Kaplan‒Meier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). CONCLUSION: The current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.

Exosome miR-3184-5p inhibits gastric cancer growth by targeting XBP1 to regulate the AKT, STAT3, and IRE1 signalling pathways.

MicroRNAs can regulate the transcription of protein-coding genes associated with the development and progression of cancer. In this study, we explored the potential diagnostic function of exosome miR-3184-5p in gastric cancer. This exosome was isolated from the blood samples of 150 patients with gastric cancer and 60 healthy participants. The mean particle size and concentration of serum exosome in the patients with gastric cancer were 104.6 nm (93.97-115.84) and 6.21e+009 particles/ml (5.15e+009-7.12e+009), respectively. miR-3184-5p expression was substantially downregulated in the patients with gastric cancer compared with that in the healthy participants. The gastric cancer cell line HGC-27 was cultured and transfected with the mimic and an inhibitor to overexpress and inhibit miR-3184-5p expression. miR-3184-5p strongly suppressed cell proliferation, migration, and invasion but induced cell apoptosis. Luciferase reporter assay revealed that XBP1 was the target of miR-3184-5p. miR-3184-5p substantially downregulated the expression of CD44, cyclin D1, MMP2, p65, p-AKT, and p-STAT3 but upregulated that of GRP78, IRE1, p-JNK, and CHOP. Moreover, miR-3184-5p cleaved caspase-12 and inhibited BCL-2 expression. These results suggested that the downregulation of miR-3184-5p in patients with gastric cancer might regulate the AKT, STAT3, and IRE1 pathways to promote the vitality of gastric cancer cells.

Nomogram to Predict Recurrence and Guide a Pragmatic Surveillance Strategy After Resection of Hepatoid Adenocarcinoma of the Stomach: A Retrospective Multicenter Study.

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.

Deciphering complex antibiotic resistance patterns in Helicobacter pylori through whole genome sequencing and machine learning.

Introduction: Helicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments. Investigating the genotype-phenotype connection for Hp using next-generation sequencing could enhance our understanding of this resistance. Methods: In this study, we analyzed 52 Hp strains collected from various hospitals. The susceptibility of these strains to five antibiotics was assessed using the agar dilution assay. Whole-genome sequencing was then performed to screen the antimicrobial resistance (AMR) genotypes of these Hp strains. To model the relationship between drug resistance and genotype, we employed univariate statistical tests, unsupervised machine learning, and supervised machine learning techniques, including the development of support vector machine models. Results: Our models for predicting Amoxicillin resistance demonstrated 66% sensitivity and 100% specificity, while those for Clarithromycin resistance showed 100% sensitivity and 100% specificity. These results outperformed the known resistance sites for Amoxicillin (A1834G) and Clarithromycin (A2147), which had sensitivities of 22.2% and 87%, and specificities of 100% and 96%, respectively. Discussion: Our study demonstrates that predictive modeling using supervised learning algorithms with feature selection can yield diagnostic models with higher predictive power compared to models relying on single single-nucleotide polymorphism (SNP) sites. This approach significantly contributes to enhancing the precision and effectiveness of antibiotic treatment strategies for Hp infections. The application of whole-genome sequencing for Hp presents a promising pathway for advancing personalized medicine in this context.

Risk factor for the development of surgical site infection following ileostomy reversal: a single-center report.

PURPOSE: Postoperative surgical site infection (SSI) is not uncommon in patients with ileostomy reversal. The appropriate index to predict the postoperative SSI in these individuals remains unclear. The aim of this study is to evaluate the risk factor for SSI after ileostomy reversal. METHODS: A consecutive cohort of 201 patients who underwent elective ileostomy reversal between January 2015 and January 2020 were retrospectively analyzed. Patients were divided into two groups: SSI group and non-SSI group. Univariate and multivariate analyses were conducted to identify risk factors for postoperative SSI. RESULTS: Postoperative SSI occurred in 37 (18.4%) patients. Compared with the non-SSI group, patients in SSI group had higher incidence of nutrition risk (56.77% vs 39.02%, P = 0.049), higher C-reactive protein (CRP) level (10.81 ± 16.49 vs 4.86 ± 4.14 mg/L, P < 0.001), and longer postoperative hospital stay (13.08 ± 3.71 vs 7.47 ± 2.38 days, P < 0.001). By analyzing the receiver-operating characteristic (ROC) curve, CRP have the value in predicting the occurrence of SSI. The areas under the ROC curves of CRP for SSI was 0.671 (95% confidence interval 0.568-0.774, P = 0.001) with an optimal diagnostic cut-off value of 8.0 mg/L. By the univariate and multivariate analyses, preoperative C-reactive protein (CRP) ≥ 8 mg/L(P < 0.001) and conventional linear closure method (P = 0.004) were independent risk factors for postoperative SSI. CONCLUSIONS: Preoperative CRP levels can be served as a predictive index for postoperative SSI after stoma reversal. Purse-string closure technique is the treatment of choice to minimize stoma site SSI in patients with stoma reversal.

Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach.

Importance: Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). Objective: To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). Design, Setting, and Participants: This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. Main Outcomes and Measures: OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Results: Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). Conclusions and Relevance: This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.

Impact of Surgical Approach on Surgical Resection Quality in Mid- and Low Rectal Cancer, A Bayesian Network Meta-Analysis.

AIM: To evaluate the evidence concerning the quality of surgical resection in laparoscopic (LapTME), robotic (RobTME) and transanal (TaTME) total mesorectal excision for mid-/low rectal cancer. METHODS: A systematic literature search of the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases was performed. A Bayesian network meta-analysis was utilized to compare surgical resection involved in these 3 surgical techniques by using ADDIS software. Rates of positive circumferential resection margins (CRMs) were the primary endpoint. RESULTS: A total of 34 articles, 2 randomized clinical trials (RCTs) and 32 non-RCTs, were included in this meta-analysis. Pooled data showed CRM positivity in 114 of 1763 LapTME procedures (6.5%), 54 of 1051 RobTME procedures (5.1%) and 60 of 1276 TaTME procedures (4.7%). There was no statistically significant difference among these 3 surgical approaches in terms of CRM involvement rates and all other surgical resection quality outcomes. The incomplete mesorectal excision rates were 9.6% (69/720) in the LapTME group, 1.9% (11/584) in the RobTME group and 5.6% (45/797) in the TaTME group. Pooled network analysis observed a higher but not statistically significant risk of incomplete mesorectum when comparing both LapTME with RobTME (OR = 1.99; 95% CI = 0.48-11.17) and LapTME with TaTME (OR = 1.90; 95% CI = 0.99-5.25). By comparison, RobTME was most likely to be ranked the best or second best in terms of CRM involvement, complete mesorectal excision, rate of distal resection margin (DRM) involvement and length of DRMs. In addition, RobTME achieved a greater mean tumor distance to the CRM than TaTME. It is worth noting that TaTME was most likely to be ranked the worst in terms of CRM involvement for intersphincteric resection of low rectal cancer. CONCLUSION: Overall, RobTME was most likely to be ranked the best in terms of the quality of surgical resection for the treatment of mid-/low rectal cancer. TaTME should be performed with caution in the treatment of low rectal cancer.

A Comprehensive Repertoire of Transfer RNA-Derived Fragments and Their Regulatory Networks in Colorectal Cancer.

To provide systematic insight into the composition and expression of transfer RNA (tRNA) derivatives transcriptome in colorectal cancer (CRC). tRNA derivatives expression profiles in three pairs of CRC and adjacent normal colon tissues were performed by tRNA-derived small RNA fragments (tRFs) and tRNA halves (tiRNA) sequencing, and microarray data of transcriptomes from CRC and paired controls were retrieved from Gene Expression Omnibus database. The differentially expressed tRFs and tiRNAs and differentially expressed genes between CRC and paired normal samples were screened. The functional regulations between tRF and tiRNA and gene were identified. A total of 60 upregulated and 48 downregulated tRNA derivatives and 7373 upregulated and 12,138 downregulated messenger RNA (mRNA) were identified. The tRF and tiRNA-gene regulatory modules were constructed by analyzing computational tRF and tiRNA-target predictions and inverse expression relationships between tRF and tiRNAs and mRNA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation showed that the function of targets of tiRNA-Tyr-GTA was mainly enriched in negative regulation of epithelial cell apoptotic process and peroxisome proliferator activated-receptors (PPAR) signaling pathway. Cellular response to monoamine stimulus and inflammatory bowel disease was enriched in function of tiRNA-Val-CAC. Two functions, including negative regulation of c-Jun N-terminal kinase (JNK) cascade and choline metabolism in cancer, were enriched in tRF-Gln-CTG. The function of mesenchymal to epithelial transition was enriched in tRF-Leu-TAG. For the first time to our knowledge, our study provided a landscape of tRNA derivatives expression profiles in CRC. Further tRF and tiRNA-gene regulatory modules construction explored the potential functions related to these tRNA derivatives in the pathogenesis of CRC.

Conditional survival and recurrence of remnant gastric cancer after surgical resection: A multi-institutional study.

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow-up strategies. A total of 298 patients were analyzed for their 3-year conditional overall survival (COS3), 3-year conditional disease-specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5-year overall survival (OS) and the 5-year disease-specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%-83.0%, Δ36.6% vs ≤T2: 82.4%-85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time-dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time-dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow-up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow-up model for RGC patients of different stages, which may affect the design of future clinical trials.

An Integrated miRNA-lncRNA Signature Predicts the Survival of Stage II Colon Cancer.

OBJECTIVE: By in silico analysis of colon cancer data from the Cancer Genome Atlas (TCGA) database, we develop a prognostic signature to improve the stratification of high-risk stage II colon cancer patients. METHOD: RNA sequencing (RNA-Seq) data from 187 stage II colon cancer patients was obtained from the TCGA data portal. We excluded cases without a sufficient amount of survival data (n=21), leaving 166 stage II colon cancer patients to be selected for further survival analysis. Differentially expressed lncRNAs and miRNAs were unveiled by the edgeR package of R. A comprehensive ceRNAs regulatory network was constructed using the Cytoscape. Cox regression analysis was performed to screen prognostic RNAs and develop a prognostic signature. The Multi Experiment Matrix and Gene Ontology were undertaken to assess the prognostic lncRNA MIR31HG function. RESULTS: The multivariate analysis indicates that 2 lncRNAs (WASIR2 and MIR31HG) and 2 miRNAs (hsa-mir-200a and hsa-mir-155) exhibited an independently significant prognostic value for stage II colon cancer. The 4 lncRNA-miRNA signatures for predicting the overall survival (OS) was constructed with the formula: Risk score=exp WASIR2*(0.213)+exp MIR31HG*(0.152)+exp hsa-mir-200a*(-0.329)+exp hsa-mir-155*(0.300). The area under the curve in the receiver operating characteristic analysis was 0.810. Kaplan-Meier survival curves confirm that the low-risk group had a low death rate, with a 5-year OS rate at 87.7%. However, the high-risk group had a low 5-year OS of 23.1% (P=0.000). The correlative genes of MIR31HG were found to be enriched in the epithelial-to-mesenchymal transition pathway, and the VEGFR3 signaling in lymphatic endothelium pathways. CONCLUSIONS: These findings indicate that the 4 lncRNA-miRNA prognostic signature could be a marker for survival of stage II colon cancer patients.

The Application of Spleen-Preserving Splenic Regional Laparoscopic Lymphadenectomy with Spleen Kept In Situ and Laparotomy with Spleen Lifted Out of the Abdomen for Locally Advanced Proximal Gastric Cancer: A Retrospective Study.

BACKGROUND AND PURPOSE: Findings whether laparoscopic lymphadenectomy with spleen kept in situ or laparotomy with spleen lifted out of the abdomen is more effective remain inconclusive. This study is aimed at comparing outcomes of spleen-preserving splenic regional laparoscopic lymphadenectomy with spleen kept in situ versus laparotomy with spleen lifted out of the abdomen for locally advanced proximal gastric cancer. METHODS: Data from patients with locally advanced proximal gastric cancer were collected from January 2011 to January 2014. A total of 246 patients were identified who received D2 radical total gastrectomy together with spleen-preserving splenic regional lymphadenectomy. Of those patients, 87 patients underwent laparoscopic splenic regional lymphadenectomy with spleen kept in situ (LSKS-SRLA) and 159 patients underwent laparotomy with spleen lifted out of the abdomen (LSLA-SRLA). Surgical outcomes and long-term outcomes were compared between the two groups. RESULTS: The total number of lymph node dissection, intraoperative blood loss volume, intraoperative injury cases, and postoperative complications had no statistically significant difference between the two groups. The number of splenic regional lymph node dissections was 3.90 ± 1.05 per case in the LSLA-SRLA group and 2.89 ± 1.04 in the LSKS-SRLA group. The operation time, length of the incision, and hospital days were shorter in the LSKS-SRLA group. The total recurrence and metastatic rates and 3-year cumulative survival rate had no statistically significant difference between the two groups. CONCLUSIONS: Similar long-term outcomes were achieved in the LSKS-SRLA and LSLA-SRLA groups for locally advanced proximal gastric cancer. However, in the aspects of surgical time, length of incision, and postoperative recovery, the LSKS-SRLA group had obvious advantages.

Development and External Validation of Web-Based Models to Predict the Prognosis of Remnant Gastric Cancer after Surgery: A Multicenter Study.

BACKGROUND: Remnant gastric cancer (RGC) is a rare malignant tumor with poor prognosis. There is no universally accepted prognostic model for RGC. METHODS: We analyzed data for 253 RGC patients who underwent radical gastrectomy from 6 centers. The prognosis prediction performances of the AJCC7th and AJCC8th TNM staging systems and the TRM staging system for RGC patients were evaluated. Web-based prediction models based on independent prognostic factors were developed to predict the survival of the RGC patients. External validation was performed using a cohort of 49 Chinese patients. RESULTS: The predictive abilities of the AJCC8th and TRM staging systems were no better than those of the AJCC7th staging system (c-index: AJCC7th vs. AJCC8th vs. TRM, 0.743 vs. 0.732 vs. 0.744; P>0.05). Within each staging system, the survival of the two adjacent stages was not well discriminated (P>0.05). Multivariate analysis showed that age, tumor size, T stage, and N stage were independent prognostic factors. Based on the above variables, we developed 3 web-based prediction models, which were superior to the AJCC7th staging system in their discriminatory ability (c-index), predictive homogeneity (likelihood ratio chi-square), predictive accuracy (AIC, BIC), and model stability (time-dependent ROC curves). External validation showed predictable accuracies of 0.780, 0.822, and 0.700, respectively, in predicting overall survival, disease-specific survival, and disease-free survival. CONCLUSIONS: The AJCC TNM staging system and the TRM staging system did not enable good distinction among the RGC patients. We have developed and validated visual web-based prediction models that are superior to these staging systems.

IL-8 interacts with metadherin promoting proliferation and migration in gastric cancer.

It has been reported that IL-8 was involved in the promotion of invasion of Gastric Cancer (GC), however the underlying mechanism by which IL-8 was observed to be able to promote invasion remains unknown. Here, in our study, IL-8 was shown to be significantly up-regulated in GC compared with paired normal control tissues whose expression was markedly associated with inferior overall prognosis; and IL-8 was displayed to be capable of directly interacting with metadherin (MTDH), which in turn can up-regulate IL-8 expression. Blockage of IL-8/MTDH using specific mono-antibody can abolish the invasion IL-8 mediated. Taken together, our results may provide a novel explanation of working mechanism of IL-8 in the invasion of GC.

KDM3A interacted with p53K372me1 and regulated p53 binding to PUMA in gastric cancer.

Chemoresistance remains a major problem in the treatment of gastric cancer patients, leading to the serious limitation of efficacy of chemotherapeutic regime. However, the underlying mechanism remains largely unknown. In our present study, we for the first time found that knock down of KDM3A can promote apoptosis induced by chemoreagent Cisplatin and Paclitaxel through p53. Mechanistically, through promoting p53 binding to the promoter of PUMA. However, knock down of KDM3A as such doesn't affect p53 level. In addition, KDM3A can interact with p53K372me1 in protein-protein interaction fashion, leading to the inactivation of p53, may eventually leading to chemoresistance of gastric cancer.