Minimizing normal tissue low dose bath for left breast Volumetric Modulated Arc Therapy (VMAT) using jaw offset.

PURPOSE: With proper beam setup and optimization constraints in the treatment planning system, volumetric modulated arc therapy (VMAT) can improve target dose coverage and conformity while reducing doses to adjacent structures for whole breast radiation therapy. However, the low-dose bath effect on critical structures, especially the heart and the ipsilateral lung, remains a concern. In this study, we present a VMAT technique with the jaw offset VMAT (JO-VMAT) to reduce the leakage and scatter doses to critical structures for whole breast radiation therapy. MATERIALS AND METHODS: The data of 10 left breast cancer patients were retrospectively used for this study. CT images were acquired on a CT scanner (GE, Discovery) with the deep-inspiration breath hold (DIBH) technique. The planning target volumes (PTVs) and the normal structures (the lungs, the heart, and the contralateral breast) were contoured on the DIBH scan. A 3D field-in-field plan (3D-FiF), a tangential VMAT (tVMAT) plan, and a JO-VMAT plan were created with the Eclipse treatment planning system. An arc treatment field with the x-jaw closed across the central axis creates a donut-shaped high-dose distribution and a cylinder-shaped low-dose volume along the central axis of gantry rotation. Applying this setup with proper multi-leaf collimator (MLC) modulation, the optimized plan potentially can provide sufficient target coverage and reduce unnecessary irradiation to critical structures. The JO-VMAT plans involve 5-6 tangential arcs (3 clockwise arcs and 2-3 counterclockwise arcs) with jaw offsets. The plans were optimized with objective functions specified to achieve PTV dose coverage and homogeneity; For organs at risk (OARs), objective functions were specified individually for each patient to accomplish the best achievable treatment plan. For tVMAT plans, optimization constraints were kept the same except that the jaw offset was removed from the initial beam setup. The dose volume histogram (DVH) parameters were generated for dosimetric evaluation of PTV and OARs. RESULTS: The D95% to the PTV was greater than the prescription dose of 42.56 Gy for all the plans. With both VMAT techniques, the PTV conformity index (CI) was statistically improved from 0.62 (3D-FiF) to 0.83 for tVMAT and 0.84 for JO-VMAT plans. The difference in the homogeneity index (HI) was not significant. The Dmax to the heart was reduced from 12.15 Gy for 3D-FiF to 8.26 Gy for tVMAT and 7.20 Gy for JO-VMAT plans. However, a low-dose bath effect was observed with tVMAT plans to all the critical structures including the lungs, the heart, and the contralateral breast. With JO-VMAT, the V5Gy and V2Gy of the heart were reduced by 32.7% and 15.4% compared to 3D-FiF plans. Significantly, the ipsilateral lung showed a reduction in mean dose (4.65-3.44 Gy) and low dose parameters (23.4% reduction for V5Gy and 10.7% reduction for V2Gy) for JO-VMAT plans compared to the 3D-FiF plans. The V2Gy dose to the contralateral lung and breast was minimal with JO-VMAT techniques. CONCLUSION: A JO-VMAT technique was evaluated in this study and compared with 3D-FiF and tVMAT techniques. Our results showed that the JO-VMAT technique can achieve clinically comparable coverage and homogeneity and significantly improve dose conformity within PTV. Additionally, JO-VMAT eliminated the low-dose bath effect at all OARs evaluation metrics including the ipsilateral/contralateral lung, the heart, and the contralateral breast compared to 3D-FiF and tVMAT. This technique is feasible for the whole breast radiation therapy of left breast cancers.

Evaluating intra-fractional tumor motion in lung stereotactic radiotherapy with deep inspiration breath-hold.

PURPOSE: To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. METHODS: Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5 mm margin in anterior-posterior (AP) and right-left (RL) directions and 8 mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. RESULTS: A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0 ± 1.9 mm, 0.1±1.5 mm, and -0.5 ± 3.7 mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4 mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4 ± 0.4 min and 3.6 ± 1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3 ± 7.9 min. CONCLUSION: Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant.

Different Methods of Minimally Invasive Esophagojejunostomy After Total Gastrectomy for Gastric Cancer: Outcomes from Two Experienced Centers.

BACKGROUND: Esophagojejunostomy after minimally invasive total gastrectomy (MITG) for gastric cancer (GC) is technically challenging. Failure of the esophagojejunal anastomosis can lead to significant morbidity, leading to short- and long-term quality of life (QoL) impairment or mortality. The optimal reconstruction method following MITG remains controversial. We evaluated outcomes of minimally invasive esophagojejunostomy after laparoscopic or robotic total gastrectomies. METHODS: We retrospectively reviewed MITG patients between 2015 and 2020 at two high-volume centers in China and the United States. Eligible patients were divided into groups by different reconstruction methods. We compared clinicopathologic characteristics, postoperative outcomes, including complication rates, overall survival rate (OS), disease-free survival rate (DFS), and patient-reported QoL. RESULTS: GC patients (n = 105) were divided into intracorporeal esophagojejunostomy (IEJ, n = 60) and extracorporeal esophagojejunostomy (EEJ, n = 45) groups. EEJ had higher incidence of wound infection (8.3% vs 13.3%, P = 0.044) and pneumonia (21.7% vs 40.0%, P = 0.042) than IEJ. The linear stapler (LS) group was inferior to the circular stapler (CS) group in reflux [50.0 (11.1-77.8) vs 44.4 (0.0-66.7), P = 0.041] and diarrhea [33.3 (0.0-66.7) vs 0.0 (0.0-66.7), P = 0.045] while LS was better than CS for dysphagia [22.2 (0.0-33.3) vs 11.1 (0.0-33.3), P = 0.049] and eating restrictions [33.3 (16.7-58.3) vs 41.7 (16.7-66.7), P = 0.029] at 1 year. OS and DFS did not differ significantly between LS and CS. CONCLUSIONS: IEJ anastomosis generated better results than EEJ. LS was associated with a better patient eating experience, but more diarrhea and reflux compared with CS. Clinical and patient-reported outcomes show the superiority of IEJ with the LS reconstruction method in MITG for GC.

FBXW2 inhibits prostate cancer proliferation and metastasis via promoting EGFR ubiquitylation and degradation.

FBXW2 is a poorly characterized F-box protein, as a tumor suppressor that inhibits growth and metastasis of lung cancer by promoting ubiquitylation and degradation of oncogenic proteins, including SKP2 and ß-catenin. However, what the biological functions of FBXW2 in prostate cancer cells and whether FBXW2 targets other substrates to involve in progression of prostate cancer is still unclear. Here, we reported that overexpression of FBXW2 attenuated proliferation and metastasis of PCa models both in vitro and in vivo, while FBXW2 depletion exhibited the opposite effects. Intriguingly, FBXW2 was an E3 ligase for EGFR in prostate cancer. EGFR protein level and its half-life were extended by FBXW2 depletion, while EGFR protein level was decreased, and its half-life was shortened upon overexpression of FBXW2, but not its dominant-negative mutant. Importantly, FBXW2 bond to EGFR via its consensus degron motif (TSNNST), and ubiquitylated and degraded EGFR, resulting in repression of EGF function. Thus, our data uncover a novel that FBXW2 as a tumor suppressor of prostate cancer, inhibits EGFR downstream by promoting EGFR ubiquitination and degradation, resulting in repression of cell proliferation and metastasis.

Evaluation of different scoring systems in the prediction of complications, morbidity, and mortality after laparoscopic radical gastrectomy.

BACKGROUND: This retrospective study aimed to assess the suitability of POSSUM and its modified versions, E-PASS and its modified score, SRS, and SORT scores for predicting postoperative complications and mortality in patients undergoing laparoscopic radical gastrectomy for gastric cancer. MATERIALS AND METHODS: Data analysis was performed on 349 patients who underwent laparoscopic radical gastrectomy at Tianjin Medical University General Hospital between January 2016 and December 2021. The discriminative ability of the scoring systems was evaluated using the area under the receiver operating characteristic curve (AUC). The primary endpoint focused on the prediction of postoperative complications, while the secondary endpoint assessed the prediction of postoperative mortality. RESULTS: Among the scoring systems evaluated, the modified E-PASS (mE-PASS) score exhibited the highest AUC (0.846) and demonstrated the highest sensitivity (81%) and specificity (79%) for predicting postoperative complications. All other scores, except for POSSUM, showed moderate discriminative ability in predicting complications. In terms of predicting postoperative mortality, the E-PASS score had the highest AUC (0.978), while the mE-PASS score displayed the highest sensitivity (76%) and specificity (90%). Notably, both E-PASS and mE-PASS scores exhibited excellent discriminative ability. CONCLUSIONS: The P-POSSUM, O-POSSUM, E-PASS, mE-PASS, SRS, and SORT scoring systems are useful tools for predicting postoperative outcomes in laparoscopic radical gastrectomy. Among them, the mE-PASS score demonstrated the best predictive power. However, the POSSUM system could only be applicable to predict postoperative mortality.

Resection of sigmoid cancer with bladder invasion using laparoscopic combined with a cystoscopic holmium laser: an innovative surgical procedure.

The aim of this study was to introduce a new surgical procedure for the resection of sigmoid colon tumours invading the bladder by combining laparoscopy and cystoscopy, and the feasibility and safety of the method were verified. The data of 6 patients with sigmoid colon cancer invading the bladder in a tertiary hospital in Chongqing from January 2020 to October 2022 were collected, sigmoid colon tumour resection was performed by this procedure, and the data related to the surgery were recorded. All six patients successfully underwent sigmoid colon tumour resection, and all sigmoid colon and bladder resections had negative margins. The mean total operative time was 211.66 ± 27.33 min, and the mean resection time of the bladder tumour was 22.16 ± 4.63 min. The median blood loss was 100 ml, and the mean number of retrieved lymph nodes was nineteen. There were no serious intraoperative complications in any of the cases. After operation, the first flatus and defecation were 4 and 4.5 days, respectively. The mean time of drainage tube retention and the time of bladder flushing were 3 and 1.5 days, respectively. The mean time of urinary tube retention was 7.5 days. There were no intestinal obstructions, dysuria, or other complications. For patients with sigmoid colon tumours invading the bladder, this method can effectively resect sigmoid colon tumours and minimize the loss of bladder tissue at the same time, which helps to prolong the survival of these patients. The surgical method is safe, reliable, and feasible.

Optimal Reconstruction After Laparoscopic Distal Gastrectomy: A Single-Center Retrospective Study.

OBJECTIVES: Although laparoscopic distal gastrectomy has been widely used for distal gastric cancer, the best functional reconstruction type has not yet been established. Based on previous experience, we propose a modified uncut Roux-en-Y anastomosis. This study aimed to compare the outcomes of different intracorporeal anastomoses after laparoscopic distal gastrectomy. METHODS: From April 2015 to August 2020, the data of 215 patients who underwent laparoscopic distal gastrectomy was collected. The patients were divided into 4 groups according to the digestive tract reconstruction method, Billroth-I, Billroth-II, Roux-en-Y, and the modified uncut Roux-en-Y. Clinicopathologic characteristics, surgery details, short-term outcomes, and postoperative nutritional status were analyzed. RESULTS: The operation time of Billroth-I anastomosis was significantly shorter (216.2 ± 25.8 min, P < .001) than that of other methods. There was no difference in postoperative complications and OS among the 4 reconstruction methods. The incidences of esophagitis, gastritis, and bile reflux were significantly lower in the Roux-en-Y and uncut Roux-en-Y group (P < .001) 1 year after surgery. And the postoperative albumin and PNI levels in uncut Roux-en-Y group were higher than those in other groups(P < .05). On multivariate analysis, age and reconstruction type were independently related to esophagitis, gastritis, and bile reflux. Serum albumin and the prognostic nutritional index were significantly higher in the uncut Roux-en-Y group than other groups (P < .05). CONCLUSIONS: All 4 reconstruction techniques are feasible and safe. The Roux-en-Y and uncut Roux-en-Y are superior to Billroth-Ⅰ and Billroth-Ⅱ+Braun in terms of reflux esophagitis, gastritis, and bile reflux. Uncut Roux-en-Y may result in better PNI than the others.

Efficacy of the Oral Administration of Maltodextrin Fructose Before Major Abdominal Surgery: A Prospective, Multicenter Clinical Study.

BACKGROUND: To study the efficacy of the oral administration of maltodextrin and fructose before major abdominal surgery (MAS). METHODS: This prospective, multicenter, parallel-controlled, double-blind study included patients aged 45-70 years who underwent elective gastrectomy, colorectal resection, or duodenopancreatectomy. The intervention group (IG) was given 800 mL and 400 mL of a maltodextrin and fructose beverage at 10 h and 2 h before MAS, respectively, and the control group (CG) received water under the same experimental conditions. The primary endpoint was insulin resistance index (IRI), and the secondary endpoints were fasting blood glucose, fasting insulin, insulin secretion index, insulin sensitivity index, intraoperative blood glucose, subjective comfort score, and clinical outcome indicators. RESULTS: A total of 240 cases were screened, of which 231 cases were randomly divided into two groups: 114 in the IG and 117 in the CG. No time-treatment effect was detected for any endpoint. The IRI and fasting insulin were significantly lower in the IG than CG after MAS (p = 0.02 & P = 0.03). The scores for anxiety, appetite, and nausea were significantly lower in the IG than CG at 1 h before MAS. Compared with baseline, the scores for appetite and nausea decreased in the IG but increased in the CG. CONCLUSION: The oral administration of maltodextrin and fructose before MAS can improve preoperative subjective well-being and reduce postoperative insulin resistance without increasing the risk of gastrointestinal discomfort.

Impact of Neoadjuvant Therapy on Minimally Invasive Surgical Outcomes in Advanced Gastric Cancer: An International Propensity Score-Matched Study.

BACKGROUND: No international consensus on the treatment of advanced gastric cancer (AGC) exists. In the absence of well-designed, comparative studies between neoadjuvant versus adjuvant strategies, concerns about increased risk of postoperative complications remain barriers to neoadjuvant chemotherapy (NAC) for AGC. We evaluated surgical outcomes of AGC patients who received minimally invasive radical gastrectomy with D2 lymphadenectomy after NAC. METHODS: We collected data from two high-volume gastric cancer programs in the United States and China between January 2015 and December 2019 with the last follow-up in February 2020. AGC patients undergoing minimally invasive radical surgery were included. After propensity score-matching, surgical outcomes were analyzed. Risk-factor of complications was analyzed in the whole cohort. RESULTS: After 1:1 propensity score-matching, 97 patients were included in each cohort. NAC + surgery cohort was younger (58.2 ± 10.3 vs. 61.3 ± 9.6, P = 0.036) with lower preoperative WBC count (5.7 ± 2.8 vs. 6.9 ± 2.1 × 109/ml) than the surgery upfront cohort. NAC was not a risk-factor for postoperative complications (odds ratio [OR], 0.859; 95% confidence interval [CI], 0.46-1.60; P = 0.633). Overall risk-factors of postoperative complications included age ≥ 60 years (OR, 21.338; 95% CI, 5.00-91.05; P < 0.001), tumor size ≥ 5 cm (OR, 1.24; 95% CI, 1.08-1.83; P < 0.001), operation time ≥ 240 min (OR, 5.53; 95% CI, 1.26-24.26; P = 0.012), and ASA classification ≥ II (OR, 13.14; 95% CI, 4.12-24.73; P < 0.001). CONCLUSIONS: NAC before minimally invasive radical gastrectomy with D2 lymphadenectomy does not increase postoperative complications, and these findings support broader application of NAC and MIS for AGC. Additional studies are required to determine the effect of NAC on long-term survival.

High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. METHODS: The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. RESULTS: CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). CONCLUSION: CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.

LINC_00355 promotes gastric cancer progression by upregulating PHF19 expression through sponging miR-15a-5p.

BACKGROUND: Long non-coding RNAs exert vital roles in several types of cancer. The objective of this study was to explore the role of LINC_00355 in gastric cancer (GC) progression and its potential mechanism. METHODS: The expression levels of LINC_00355 in GC tissues and cells were detected by quantitative real-time PCR, followed by assessing the effects of LINC_00355 knockdown or overexpression on cell properties. Dual-luciferase reporter assay was utilized to identify the relationship between LINC_00355 and microRNA (miR)-15a-5p and miR-15a-5p and PHD finger protein 19 (PHF19), followed by the rescue experiments. RESULTS: The results showed that LINC_00355 was highly expressed in GC tissues and cells compared with the corresponding control. LINC_00355 knockdown decreased the viability, migration, and invasion and increased the accumulation of GC cells in G1 phase and apoptosis. Meanwhile, LINC_00355 downregulation markedly increased cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase protein levels, whereas decreased cyclin D1, cyclin E, matrix metalloproteinase (MMP) 9, MMP2, and N-cadherin protein levels in GC cells. However, LINC_00355 overexpression had the opposite effects. It was verified that LINC_00355 upregulated the expression of PHF19 through sponging miR-15a-5p. Furthermore, PHF19 overexpression reversed the effect of LINC_00355 knockdown on GC cell properties, including cell viability, migration, invasion, and apoptosis. CONCLUSIONS: Collectively, these results suggest that LINC_00355 promotes GC progression by up-regulating PHF19 through sponging miR-15a-5p. Our findings may provide an important clinical basis for reversing the malignant phenotype of GC.

The protocol of a prospective, multicenter, randomized, controlled phase III study evaluating different cycles of oxaliplatin combined with S-1 (SOX) as neoadjuvant chemotherapy for patients with locally advanced gastric cancer: RESONANCE-II trial.

BACKGROUND: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. DISCUSSION: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. TRIAL REGISTRATION: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

Which Staging System Is More Suitable for Gastric Neuroendocrine Cancer and Mixed Adenoneuroendocrine Carcinomas? A Multicenter Cohort Study.

PURPOSE: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). METHODS: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. RESULTS: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. CONCLUSIONS: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

Construction and Validation of a Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer.

BACKGROUND: Increasing evidence indicated that the tumor microenvironment (TME) plays a critical role in tumor progression. This study aimed to identify and evaluate mRNA signature involved in lymph node metastasis (LNM) in TME for gastric cancer (GC). METHODS: Gene expression and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to evaluate the TME of GC. The heatmap and Venn plots were applied for visualizing and screening out intersect differentially expressed genes (DEGs) involved in LNM in TME. Functional enrichment analysis, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were also conducted. Furthermore, binary logistic regression analysis were employed to develop a 4-mRNAs signature for the LNM prediction. ROC curves were applied to validate the LNM predictive ability of the riskscore. Nomogram was constructed and calibration curve was plotted to verify the predictive power of nomogram. RESULTS: A total of 88 LNM related DEGs were identified. Functional enrichment analysis and GSEA implied that those genes were associated with some biological processes, such as ion transportation, lipid metabolism and thiolester hydrolase activity. After univariate and multivariate logistic regression analysis, 4 mRNAs (RASSF2, MS4A2, ANKRD33B and ADH1B) were eventually screened out to develop a predictive model. ROC curves manifested the good performance of the 4-mRNAs signature. The proportion of patients with LNM in high-risk group was significantly higher than that in low-risk group. The C-index of nomogram from training and test cohorts were 0.865 and 0.765, and the nomogram was well calibrated. CONCLUSIONS: In general, we identified a 4-mRNAs signature that effectively predicted LNM in GC patients. Moreover, the 4-mRNAs signature and nomogram provide a guidance for the preoperative evaluation and postoperative treatment of GC patients.

Multi-institutional development and validation of a nomogram to predict recurrence after curative resection of gastric neuroendocrine/mixed adenoneuroendocrine carcinoma.

OBJECTIVE: To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. BACKGROUND: Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. METHODS: A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). RESULTS: The median follow-up time was 40 months (1-169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). CONCLUSIONS: Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.

Primary extraskeletal osteosarcoma of sigmoid mesocolon: a case report and a review of the literature.

BACKGROUND: Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal malignancy, which produces osteoid, bone, or chondroid material and is located in the soft tissue without attachment to skeletal bones and periosteum. One of the things that ESOS originated from mesentery is much rarer. CASE PRESENTATION: A 75-year female had a history of pain in the left lower abdomen for more than 4 months. Abdominal computerized tomography (CT) and magnetic resonance imaging revealed a large, irregular, and solid-cystic mass (largest diameter was 11.5 cm). The tumor was radically removed during an open operation. It was composed of abundant osteoid and polyhedral-shaped tumor cells with high atypia and high mitotic activity microscopically. The final pathological diagnosis was osteoblastic osteosarcoma, arising from the sigmoid mesocolon with negative margins. A 9-month follow-up by CT exhibited signs of peritoneal metastasis. CONCLUSIONS: Given the rarity of cases of mesenteric ESOS, diagnosis mainly depended on pathology findings or should be taken into consideration when the mesenteric mass was found. Its most effective treatment had not been determined, with surgical excision being generally accepted. Ensuring negative surgical margins may be an important factor affecting prognosis.

Calcium-activated nucleotidase 1 silencing inhibits proliferation, migration, and invasion in human clear cell renal cell carcinoma.

Calcium-activated nucleotidase 1 (CANT1, belongs to the apyrase family, is widely expressed in various organs. However, the biological function of CANT1 remains poorly explored. In this study, we aimed to investigate the expression profile and functions of CANT1 in clear cell renal cell carcinoma (ccRCC). Our data show that the protein level of CANT1 was significantly higher in tumor tissues than in adjacent normal tissues. CANT1 silencing suppressed cell proliferation, migration, and invasion obviously in 769-P and 786-O cells, arrested cell cycle in S phase and promoted apoptosis in 769-P cells. In conclusion, the present study shows the different expression mode of CANT1 in human ccRCC tumor tissue and adjacent normal tissue, denotes the function of CANT1 in ccRCC cells and provides potential molecular mechanisms and pathways of CANT1 antitumor function in ccRCC.

Perioperative and long-term results of retroperitoneal laparoscopic pyelolithotomy versus percutaneous nephrolithotomy for staghorn calculi: a single-center randomized controlled trial.

PURPOSE: To compare the perioperative and long-term outcomes of retroperitoneal laparoscopic pyelolithotomy (RLP) and percutaneous nephrolithotomy (PCNL) for the treatment of staghorn calculi. METHODS: From May 2011 to March 2017, eligible patients with staghorn calculi were randomly assigned to two groups: RLP and PCNL. Patients underwent the operations prospectively. Subsequently, a follow-up protocol was performed. Perioperative data related to the efficacy, safety and long-term outcomes (stone recurrence and functional changes in the affected kidney) were comparatively analyzed between the two groups. RESULTS: Overall, 105 patients underwent surgical treatment, including 51 in the RLP group and 54 in the PCNL group. There was no difference in demographics or stone characteristics between the two groups. The single-session stone-free rate (SFR) was higher (88.2% vs. 64.8%), the mean hemoglobin drop was lower (0.4 ± 0.3 vs. 1.7 ± 0.9 g/dL), the rate of postoperative fever was lower (5.9% vs. 20.4%), but operative time was longer (135.7 ± 35.5 vs. 101.9 ± 41.2 min) and the total cost was more expensive (5546 ± 772 vs. 3861 ± 402 USD)in the RLP group than in the PCNL group (all p < 0.05). The mean increase in the split function (8.3 ± 3.1 vs. 4.2 ± 2.4 mL/min) and the rate of improvement of the affected kidney (56.3% vs. 35.3%) were significantly higher in the RLP group than in the PCNL group at 1 year after surgery (both p < 0.05). However, the rate of stone recurrence was similar between the groups at a mean follow-up of 47.3 ± 18.6 months. CONCLUSIONS: PCNL remains the first-line treatment for most cases of staghorn calculi. Nevertheless, in some selected cases with the extrarenal and dilated pelvis, RLP can be considered as an alternative management of staghorn calculi, which was associated with a high single-session SFR, low rates of complications, and better functional preservation of the affected kidney.

Anatomical variation of infra-pyloric artery origination: A prospective multicenter observational study (IPA-Origin).

OBJECTIVE: Infra-pyloric artery (IPA) is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA. METHODS: We did this prospective, multicenter, open-label, observational study at gastric surgery departments of 34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ2 tests and Fisher's tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov (No. NCT03071237). RESULTS: Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419 (97.7%) patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398 (95.0%) patients, including gastroduodenal artery (GDA) in 154 (36.8%) patients, anterior superior pancreaticoduodenal artery (ASPDA) in 130 (31.0%) patients, and right gastroepiploic artery (RGEA) in 114 (27.2%) patients. Fifteen (3.6%) patients were identified with multiple IPA and 6 (1.4%) patients were identified as IPA absence. The differences in the distribution of surgical approach (P=0.003) and geographic area (P=0.030) were statistically significant. No difference was shown in sex, age, gastrectomy type, tumor location, and clinical T, N and M stage. CONCLUSIONS: Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions. Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.