Prognostic significance of preoperative serum tumor markers in hepatoid adenocarcinoma of stomach (HAS).

BACKGROUND: The role of preoperative serum tumor markers in HAS patients was vague, we designed the study to explore the effect of preoperative serum tumor markers on predicting the prognosis of HAS patients. METHODS: A total of 139 patients were included according to the different tumor makers. X-tile tool was employed to identify the optimal cut-off values of respective tumor makers. Multivariate analyses were conducted to determine independent risk factors. RESULTS: The optimal cut-off value of alpha-fetoprotein (AFP) for 3-years overall survival (OS) and recurrence-free survival (RFS) was 516 ng/mL. Patients with high-level AFP values assumed significantly worse OS and RFS than those with low-level AFP values (P = 0.028 and P = 0.011, respectively). The optimal cut-off value of Carbohydrate antigen (CA)19-9 for OS and RFS was 51.3 U/mL. And the survival results were similar with AFP in the aspects of OS and RFS (P = 0.009 and P < 0.001, respectively). Multivariate analyses showed that high serum AFP was an independent risk factor for OS and RFS of HAS patients (HR7.264; 95% CI 1.328-39.738; P = 0.022 and HR 2.688; 95% CI 0.922-7.836; P = 0.070, respectively). CA19-9 could perform as a fair substitute to predict the HAS patients' OS and RFS when the preoperative serum AFP was unavailable (HR 7.816; 95% CI 2.084-29.308; P = 0.002 and HR 4.386; 95% CI 1.824-10.547; P = 0.001, respectively). Other tumor markers didn't present significant influences. CONCLUSIONS: Applying preoperative serum AFP level to predict the HAS patients' prognosis is feasible and preoperative serum high-AFP is an independent risk factor for OS and RFS of HAS patients. Preoperative serum CA19-9 could be an alternative choice when AFP was absent.

Double-tract reconstruction is superior to esophagogastrostomy in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy: Results from a prospective randomized controlled clinical trial in China.

Objective: The aim of this study was to prospectively compare double-tract reconstruction (DTR) and esophagogastrostomy (EG) after proximal gastrectomy (PG) regarding the incidence of reflux esophagitis, quality of life (QOL), nutritional status and surgical safety. Methods: This study was a randomized controlled trial. Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group. The characteristics of patients, parameters for surgical safety, incidence of reflux esophagitis, nutrition status and QOL were collected and compared between the two groups. Univariate analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after PG. Results: Thirty-seven patients of the EG group and 36 patients of the DTR group were enrolled. The incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group (8.3% vs. 32.4%, P=0.019). The DTR group demonstrated a more favorable QOL than the EG group after PG. The nutritional status was balanced within the EG group and the DTR group. The operation time was longer in the DTR group than in the EG group (191 min vs. 221 min, P=0.001), while surgical safety was similar in the two groups. Conclusions: Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.

Molecular mechanism of high-production tannase of Aspergillus carbonarius NCUF M8 after ARTP mutagenesis: revealed by RNA-seq and molecular docking.

BACKGROUND: Tannase is an enzyme produced by microbial fermentation and is widely used in the food industry; however, the molecular mechanism of tannase production by Aspergillus has not yet been studied. This study was conducted to reveal the differences in Aspergillus carbonarius tannase enzymatic characterization, secondary structures and molecular mechanisms after treatment of the strain with atmospheric and room temperature plasma (ARTP). RESULTS: The results showed that the specific activity of tannase was improved by ARTP treatment, and it showed higher thermostability and tolerance to metal ions and additives. The enzymatic characterization and molecular docking results indicated that tannase had a higher affinity and catalytic rate with tannic acid as a substrate after ARTP treatment. In addition, the docking results indicated that Aspergillus tannases may catalyze tannic acid by forming two hydrogen-bonding networks with neighboring residues. RNA-seq analysis indicated that changes in steroid biosynthesis, glutathione metabolism, glycerolipid metabolism, oxidative phosphorylation pathway and mitogen-activated protein kinase signaling pathways might be crucial reasons for the high production of tannase. CONCLUSION: ARTP enhanced the yield and properties of A. carbonarius tannase by changing the enzyme structure and cell metabolism. This study provides a theoretical basis for elucidating the molecular mechanism underlying high production of Aspergillus tannases. © 2022 Society of Chemical Industry.

Characteristics of lymph node stations/basins metastasis and construction and validation of a preoperative combination prediction model that accurately excludes lymph node metastasis in early gastric cancer.

Objective: To explore the candidate indications for function-preserving curative gastrectomy and sentinel lymph node navigation surgery in early gastric cancer (EGC). Methods: The clinicopathological data of 561 patients with EGC who underwent radical gastrectomy for gastric cancer at Peking University Cancer Hospital from November 2010 to November 2020 with postoperative pathological stage pT1 and complete examination data, were collected. Pearson's Chi-square test was used and binary logistic regression was employed for univariate and multivariate analyses. Combined analysis of multiple risk and protective factors for lymph node metastasis (LNM) of EGC was performed. A negative predictive value (NPV) combination model was built and validated. Results: LNM occurred in 85 of 561 patients with EGC, and the LNM rate was 15.15%. NPV for LNM reached 100% based on three characteristics, including ulcer-free, moderately well differentiation and patient <65 years old or tumor located at the proximal 1/3 of the stomach. Regarding lymphatic basin metastasis, multivariate analysis showed that the metastatic proportion of the left gastric artery lymphatic basin was significantly higher in male patients compared with female patients (65.96% vs. 38.89%, P<0.05). The proportion of right gastroepiploic artery lymphatic basin metastasis in patients with a maximum tumor diameter >2 cm was significantly greater than that noted in patients with a maximum tumor diameter ≤2 cm (60.78% vs. 28.13%, P<0.05). Conclusions: Characteristics of lymph node stations/basins metastasis will facilitate precise lymph node resection. The NPV for LNM reaches 100% based on the following two conditions: young and middle-aged EGC patients, well-differentiated tumors, and without ulcers; or well-differentiated tumors, without ulcers, and tumors located in the proximal stomach. These findings can be used as the recommended indications for function-preserving curative gastrectomy and sentinel lymph node navigation surgery.

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effect of Additional Trastuzumab in Neoadjuvant and Adjuvant Treatment for Patients with Resectable HER2-Positive Gastric Cancer.

BACKGROUND: Recent studies have reported a beneficial role of trastuzumab in neoadjuvant treatment (NAT) among resectable gastric cancer (GC) patients; however, the effect of adjuvant treatment (AT) combined with trastuzumab is understudied. We performed a retrospective cohort study to compare chemotherapies with or without trastuzumab among human epidermal growth factor receptor 2-positive (HER2 +) locally advanced GC patients in the AT and NAT settings, respectively. METHODS: We enrolled 208 HER2 + resected GC patients who underwent perioperative/postoperative treatment in 2010-2019 in a single-centered hospital, including 135 AT patients and 73 NAT patients. We used inverse probability of treatment weighting (IPTW) to balance potential confounding factors between the treatment groups, and estimated the treatment effect of trastuzumab. Pathological and survival outcomes were evaluated. RESULTS: The number of trastuzumab-exposed patients in the AT and NAT cohorts was 31 (23.0%) and 34 (46.6%), respectively. After IPTW adjustment, AT combined with trastuzumab showed a better overall survival (OS) over chemotherapy alone (p = 0.023). In IPTW-adjusted NAT analysis, trastuzumab-exposed patients had an improvement in tumor pathological regression and downstaging, with lower tumor regression grade scores (p = 0.002), ypTNM stages (p < 0.001), ypN stages (p = 0.035), and ypT stages (p < 0.001). Loss of HER2 positivity following trastuzumab treatment was observed in NAT patients; however, we did not observe any significant effect of trastuzumab on OS (p = 0.126). CONCLUSIONS: Given the improvement in tumor regression and downstaging among NAT patients, and the OS benefit in AT patients, trastuzumab could be considered a promising treatment for locally advanced HER2 + GC patients. In particular, re-evaluation of HER2 status should be considered following NAT combined with trastuzumab.

Construction and Validation of a Risk-Scoring Model that Preoperatively Predicts Lymph Node Metastasis in Early Gastric Cancer Patients.

OBJECTIVE: The aim of this study was to create a risk-scoring model to preoperatively predict the incidence of lymph node metastasis (LNM) in early gastric cancer (EGC) patients to guide treatment. METHODS: To construct the risk-scoring model, we retrospectively analyzed a primary cohort of 548 EGC patients. Univariate analysis and logistic regression were performed. A risk-scoring model for predicting LNM in EGC patients was developed based on preoperative factors, and another cohort of 73 patients was then analyzed to validate the model. RESULTS: In the primary cohort, LNM was pathologically confirmed in 72 (13.1%) patients. In the multivariate analysis, the presence of ulceration and tumor size on gastroscopy, undifferentiated histological type, and presence of enlarged lymph nodes on computed tomography or endoscopic ultrasonography were independent risk factors for LNM. A 17-point risk-scoring model was developed to predict LNM risk. The cut-off score of the model was 8, and the area under the receiver operating characteristic curve (AUC) of the model was 0.835 [95% confidence interval (CI) 0.784-0.886]. In the validation cohort, the AUC of the model was 0.829 (95% CI 0.699-0.959). CONCLUSIONS: We developed and validated an effective 17-point risk-scoring model that could preoperatively predict LNM for EGC patients.

Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery.

BACKGROUND: HIPEC is an emerging procedure to treat peritoneal metastasis of gastric cancer. Data about HIPEC in locally advanced gastric cancer is scarce. The purpose of this trial is to evaluate the safety and toxicity of prophylactic HIPEC with cisplatin for patients with locally advanced gastric cancer. METHODS: From March 2015 to November 2016, a prospective, randomized phase II trial was conducted. After radical gastrectomy, patients in the experimental group underwent HIPEC with cisplatin followed by adjuvant chemotherapy with SOX regime. Patients in the other group were treated with SOX regime alone. Postoperative complications and patient survival were compared. RESULTS: In total, 50 patients were eligible for analyses. No significant difference was found in the incidence of postoperative complications including anastomotic/intestinal leakage, liver dysfunction, bone marrow suppression, wound infection and ileus (P > 0.05). Mean duration of hospitalization after radical gastrectomy was 11.7 days. 12.2 days in experimental group and 10.8 days in control group respectively (P = 0.255). The percentage of patients with elevated tumor markers was 12.1% in experimental group, which was significantly lower than 41.2% in control group (P = 0.02). 3-year RFS of patients who treated with or without prophylactic HIPEC were 84.8 and 88.2% respectively (P = 0.986). In the multivariate analysis, pathological T stage was the only independent risk factor for the RFS of patients (P = 0.012, HR =15.071). CONCLUSION: Additional intraoperative HIPEC with cisplatin did not increase postoperative complications for locally advanced gastric cancer after curative surgery. Prophylactic HIPEC with cisplatin was safe and tolerable, while it did not reduce the risk of peritoneal recurrence in this trial, supporting further studies to validate the efficacy of it. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038331. Registered 18 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=59692 .

ASB16-AS1 up-regulated and phosphorylated TRIM37 to activate NF-κB pathway and promote proliferation, stemness, and cisplatin resistance of gastric cancer.

BACKGROUND: Long non-coding RNA (lncRNA) ASB16 antisense RNA 1 (ASB16-AS1) is recognized as an oncogene in several cancer types, but its relation to GC is unknown. Tripartite motif containing 37 (TRIM37) has been proven to accelerate the development of gastric cancer (GC), whereas the molecular mechanism assisted ASB16-AS1 and TRIM37 in regulating GC progression remains unclear. METHODS: Differentially expressed lncRNAs in GC samples were analyzed based on Gene Expression Omnibus (GEO) data. CCK-8 and colony formation assays were applied to determine the proliferative ability of GC cells. Stem cell-like phenotype of GC cells was assessed by sphere formation assay and flow cytometry analysis. Luciferase reporter assay, RNA immunoprecipitation (RIP), pulldown, and co-immunoprecipitation (Co-IP) were performed to verify the interplay of RNA molecules. RESULTS: ASB16-AS1 was upregulated in GC samples according to GEO data and qRT-PCR analysis. ASB16-AS1 strengthened the proliferative ability and stem cell-like characteristics in GC cells. More importantly, ASB16-AS1 encouraged GC cell growth in vivo. Mechanistically, ASB16-AS1 strengthened TRIM37 expression by sequestering miR-3918 and miR-4676-3p. ASB16-AS1 activated NF-kappa B (NF-κB) pathway by cooperating with ATM serine/threonine kinase (ATM) to induce TRIM37 phosphorylation. CONCLUSION: In summary, ASB16-AS1 exerted oncogenic functions in GC through modulating TRIM37 expression at both mRNA and protein levels.

Identification of lymph node metastasis by computed tomography in early gastric cancer.

OBJECTIVE: Lymph node status is critical when selecting treatment methods for patients with early gastric cancer (EGC). The aim of this study was to assess the diagnostic value of computed tomography (CT) for detection of lymph node metastasis (LNM) in patients with EGC. METHODS: We retrospectively analyzed patients who had pathologically confirmed EGC between November 2010 and January 2019. After 1:1 propensity score matching, 65 patients with LNM and 65 patients without LNM were retained for comparison. The long diameter (LD) and short diameter (SD) of all visualized lymph nodes in all stations were recorded. The diagnostic value of LNM was assessed with receiver operating characteristic analysis. RESULTS: Among 130 patients, we found a total of 558 lymph nodes on the CT images. Among the diagnostic indicators, the number, sum of LD and sum of SD of lymph nodes greater than 3 mm had better discrimination. The areas under the curve were all greater than 0.75. As for different regions, the optimal cutoff values of number, the sum of LD and sum of SD were determined as follows: overall, ≥4, 19.9 mm and 13.5 mm; left gastric artery basin, ≥3, 15.7 mm and 8.6 mm; right gastroepiploic artery basin, ≥2, 8.6 mm and 7.0 mm. CONCLUSIONS: CT is valuable for diagnosing LNM in EGC patients. The number, sum of LD and sum of SD of lymph nodes greater than 3 mm are preferable indicators. Different regional lymph nodes have different optimal criteria for predicting LNM in ECG patients.

The prognosis of hepatoid adenocarcinoma of the stomach: a propensity score-based analysis.

BACKGROUND: To investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach (HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery. METHODS: We retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. The relationships between gastric cancer type and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression. RESULTS: Our data demonstrate that there was no statistically significant difference in the OS between HAS and non-HAS {K-M, P = log rank (Mantel-Cox), (before PSM P = 0.397); (1:1 PSM P = 0.345); (1:2 PSM P = 0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching). CONCLUSION: HAS was generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.

Screening of tea saponin-degrading strain to degrade the residual tea saponin in tea seed cake.

Although tea seed cake (TSC) possesses high nutritional value, its high content of tea saponin (TS) limits its potential as feed. This study aimed to degrade TS in TSC by saponin-degrading strain and used a multistrains fermentation method to improve its nutritional value and palatability. Three saponin-degrading strains were isolated from Oleum Camelliae mill soil and identified as Citrobacter sp. FCTS301, Pantoea sp. FCTS302, and Enterobacter sp. FCTS303. Single-factor experiment showed that Citrobacter sp. FCTS301 had the highest degradation rate of TS. Response surface analysis for Citrobacter sp. FCTS301 indicated that the optimum culture conditions were as follows: initial pH of 7.2, culture temperature of 34.2 °C, inoculation amount of 7.3%, the agitation rate of 150 rpm, and the TS concentration of 10.0 g/L. Under these conditions, the maximum degradation rate was 82.6%. The fermentation process of TSC was obtained by a multistrains fermentation experiment. Considering the protein content, crude fiber degradation rate, and TS degradation rate of each group, the optimum inoculum amount of strains included Citrobacter sp. FCTS301, Aspergillus oryzae NCUF414, Saccharomyces cersvisiae NCUF306.5, and Lactobacillus plantarum NCUF201.1(5%, 0.5%, 1.0%, and 1.5%). After TS was degraded efficiently, fermented TSC can be presumed a potential feed raw material.

Impact of postoperative major complications on long-term survival after radical resection of gastric cancer.

BACKGROUND: This study was designed to evaluate the impact of postoperative major complications on long-term survival following curative gastrectomy. METHODS: This retrospective study included 239 patients with gastric cancer undergoing gastrectomy at the Beijing Cancer Hospital from February 2012 to January 2013. Survival curves were compared between patients with major complications (mC group) and those without major complications (NmC group). Multivariate analysis was conducted to identify independent prognostic factors. RESULTS: Postoperative complication and mortality rates were 24.7 and 0.8%, respectively. The severity of complications was graded in accordance with the Clavien-Dindo classification. The incidence of minor complications (grades I-II) and major complications (grades III-V) was 9.2 and 15.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were better in the NmC group than in the mC group (p = 0.014, p = 0.013). Multivariate analysis identified major complications as an independent prognostic factor for OS and DFS. After stratification by pathological stage, this trend was also observed in stage II patients. CONCLUSIONS: Postoperative major complications adversely affect OS and DFS. The prevention and early diagnosis of complications are essential to minimize the negative effects of complications on surgical safety and long-term patient survival.

Diagnostic value of negative enrichment and immune fluorescence in situ hybridization for intraperitoneal free cancer cells of gastric cancer.

OBJECTIVE: To explore the intraperitoneal free cancer cell (IFCC) detection value of negative enrichment and immune fluorescence in situ hybridization (NEimFISH) on chromosomes (CEN) 8/17. METHODS: To verify the reliability of NEimFISH, 29 gastric cancer tumors, their adjacent tissues and greater omental tissues were tested. Our study then included 105 gastric cancer patients for IFCC. We defined patients as IFCC-positive if a signal was detected, regardless of the detailed cancer cell numbers. A comparison of clinicopathological features was conducted among IFCC groups. We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods. The comparison of IFCC number was also conducted among different groups. RESULTS: A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97% of malignant tissue samples in our study. Compared to intestinal gastric cancer, patients with diffuse gastric cancer tended to have more IFCCs (6 vs. 4, P=0.002). The IFCC counts were often higher in the lymphovascular invasion positive group than negative group (3 vs. 1, P=0.022). All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH. When compared to conventional cytology and paraffin pathology, NEimFISH had a higher IFCC positive rate (68.9%) and higher one-year peritoneal recurrence predictive value with area under the curve (AUC) of 0.922. CONCLUSIONS: Gastric cancer could be effectively diagnosed by NEimFISH. The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer. NEimFISH is a reliable detection modality with a higher positive detection rate, higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.

The effect of preoperative treatments on lymph node counts after total gastrectomy in esophagogastric adenocarcinoma.

OBJECTIVES: This study aims to explore the effects of preoperative treatments on lymph nodes (LNs) counts after total gastrectomy with D2 lymphadenectomy in esophagogastric adenocarcinoma. METHODS: A retrospective analysis was performed for 446 patients with locally advanced esophagogastric adenocarcinoma. The patients were divided into three groups: surgery first (SF), preoperative chemotherapy (PCT), and preoperative chemoradiotherapy (PCRT). Clinical-pathological data were analyzed. RESULTS: The case number in SF, PCT, and PCRT groups was 281, 109, and 56, respectively, and the median total LNs count was 32.0 (10.0-102.0), 31.0 (12.0-62.0), and 25.5 (10.0-50.0), respectively, (P < 0.001). Univariate and multivariate analyses demonstrated the total LNs count was lower in PCRT than SF/PCT (P < 0.001), and had no correlation with tumor regression grades (TRGs). Subgroup comparison showed radiation target LNs count was lower in PCRT than SF/PCT (P < 0.001), and peritarget LNs count was lower in PCRT than SF (P = 0.002). CONCLUSION: For esophagogastric adenocarcinoma, PCRT reduced total LNs count after total gastrectomy with D2 lymphadenectomy, whereas PCT did not. In the PCRT group, LNs count was lower in both radiation target and peritarget areas than in the SF group but only in radiation target area than in the PCT group. The correlation between TRGs and total LNs count remained unclear.

The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results from a Chinese mono-institutional study of 1663 patients.

BACKGROUND: We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer. METHODS: The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed. RESULTS: In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value. CONCLUSIONS: The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.

Construction and external validation of a nomogram that predicts lymph node metastasis in early gastric cancer patients using preoperative parameters.

OBJECTIVE: To create a nomogram to predict the incidence of lymph node metastasis (LNM) in early gastric cancer (EGC) patients and to externally validate the nomogram. METHODS: To construct the nomogram, we retrospectively analyzed a primary cohort of 272 EGC patients. Univariate analysis and a binary logistic regression were performed. A nomogram predicting the incidence of LNM in EGC patients was created. The discrimination ability of the nomogram was measured using the concordance index (c-index), and the nomogram was also calibrated. Then, another prospective cohort of 81 patients was analyzed to validate the nomogram. RESULTS: In the primary cohort, LNM was pathologically confirmed in 37 (13.6%) patients. In multivariate analysis, the presence of an ulcer, the maximum lesion diameter observed via gastroscopy, the thickness of the lesion observed via endoscopic ultrasonography, and the presence of enlarged lymph nodes on computed tomography (CT) were independent risk factors for LNM. A nomogram was then created based on the regression model with the c-index of 0.905, and the calibration curve of the nomogram fell approximately on the ideal 45-degree line. The cut-off score of the nomogram was 110, and the sensitivity, specificity, positive predictive and negative predictive values of the nomogram in the primary cohort were 81.1%, 86.0%, 47.6% and 96.7%, respectively, and in the prospective validation cohort were 75.0%, 91.0%, 60.0% and 95.5%, respectively. The calibration curve of the external validation cohort was almost on the 45-degree line. CONCLUSIONS: We developed an effective nomogram predicting the incidence of LNM for EGC patients.

Prognostic significance of the total number of harvested lymph nodes for lymph node-negative gastric cancer patients.

BACKGROUND: The relationship between the number of harvested lymph nodes (HLNs) and prognosis of gastric cancer patients without an involvement of lymph nodes has not been well-evaluated. The objective of this study is to further explore this issue. METHODS: We collected data from 399 gastric cancer patients between November 2006 and October 2011. All of them were without metastatic lymph nodes. RESULTS: Survival analyses showed that statistically significant differences existed in the survival outcomes between the two groups allocated by the total number of HLNs ranging from 16 to 22. Therefore, we adopted 22 as the cut-off value of the total number of HLNs for grouping (group A: HLNs <22; group B: HLNs≥22). The intraoperative and postoperative characteristics, including operative blood loss (P=0.096), operation time (P=0.430), postoperative hospital stay (P=0.142), complications (P=0.552), rate of reoperation (P=0.966) and postoperative mortality (P=1.000), were comparable between the two groups. T-stage-stratified Kaplan-Meier analyses revealed that the 5-year survival rate of patients at the T4 stage was better in group B than in group A (76.9% vs. 58.5%; P=0.004). An analysis of multiple factors elucidated that the total number of HLNs, T stage, operation time and age were independently correlated factors of prognosis. CONCLUSIONS: Regarding gastric cancer patients without the involvement of lymph nodes, an HLN number ≥22 would be helpful in prolonging their overall survival, especially for those at T4 stage. The total number of HLNs was an independent prognostic factor for this population of patients.

The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival.

BACKGROUND: The optimal extent of gastrectomy for middle-third gastric cancer remains controversial. In our study, the short-term effects and longer-term survival outcomes of distal subtotal gastrectomy and total gastrectomy are analysed to determine the optimal extent of gastrectomy for middle-third gastric cancer. METHODS: We retrospectively collect and analyse clinicopathologic data and follow-up outcomes from a prospectively collected database at the Peking University Cancer Hospital. Patients with middle-third gastric adenocarcinoma who underwent curative resection are enrolled in our study. RESULTS: We collect data of 339 patients between January 2005 and October 2011. A total of 144 patients underwent distal subtotal gastrectomy, and 195 patients underwent total gastrectomy. Patients in the total gastrectomy group have longer operative duration (P < 0.001) and postoperative hospital stay (P = 0.001) than those in the distal subtotal gastrectomy group. In the total gastrectomy group, more lymph nodes are harvested (P < 0.001). Meanwhile, the rate of postoperative complications is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (8% vs 15%, P = 0.047). Further analysis demonstrates that the rate of anastomosis leakage is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (0% vs 4%, P = 0.023). Kaplan-Meier (log rank test) analysis shows a significant difference in overall survival between the two groups. The 5-year overall survival rates in the distal subtotal gastrectomy and total gastrectomy groups are 65% and 47%, respectively (P < 0.001). Further stage-stratified analysis reveals that no statistical significance exists in 5-year survival rate between the distal subtotal gastrectomy and total gastrectomy groups at the same stage. Multivariate analysis shows that age (P = 0.046), operation duration (P < 0.001), complications (P = 0.037), usage of neoadjuvant chemotherapy (P < 0.001), tumor size (P = 0.012), presence of lymphovascular invasion (P = 0.043) and N stage (P < 0.001) are independent prognostic factors for survival. CONCLUSIONS: For patients with middle-third gastric cancer, distal subtotal gastrectomy shortens the operation duration and postoperative hospital stay and reduces postoperative complications. Meanwhile, the long-term survival of patients with distal subtotal gastrectomy is similar to that of those with total gastrectomy at the same stage. The extent of gastrectomy for middle-third gastric cancer is not an independent prognostic factor for survival.

Depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis.

OBJECTIVE: Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. METHODS: Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer (cT≥2M0). We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination (P) and cytology results (CY). Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic (ROC) analysis were performed in training set to find out risk factors of intra-abdominal metastasis, and then validate it in testing set. RESULTS: Out of 249 cM0 patients, 51 (20.5%) patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 (8.0%) P1CY1, 17 (6.8%) P0CY1 and 14 (5.6%) P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography (CT) scan ≥21 mm and tumor-occupied ≥2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. CONCLUSIONS: According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis.