Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND AND AIMS: When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC. METHODS: The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%. RESULTS: We identified 1516 patients with non-ulcerated T1a tumors ≤2 cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0 cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9 cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type. CONCLUSION: In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9 cm or less, regardless of histologic type.

Changes in working status after cancer diagnosis and socio-demographic, clinical, work-related, and psychological factors associated with it.

BACKGROUND: While many studies investigated changes in working status in cancer survivors, most studies have been performed in survivors of breast cancer and few studies evaluated factors associated with changes in the working status of cancer survivors comprehensively. We aimed to evaluate the changes in the working status of cancer survivors after diagnosis and socio-demographic, clinical, work-related and psychological factors associated with it. METHODS: We conducted a cross-sectional survey of adult patients with cancer who were working at the time of diagnosis. A trained interviewer inquired about participants' current working status, including leave of absence, discontinuing, continuing, and changing work. Sociodemographic, clinical, work-related and psychological factors were measured. Multinomial logistic regression was used to identify factors associated with changes in the working status. RESULTS: Among the 730 patients, 29%, 18% and 6% were currently on a discontinued working, leave of absence and had changed jobs, respectively. Patients who discontinued working after cancer diagnosis were more likely to be female, have ≥ $3,000 of monthly family income, not be the principal wage earners for their families and be blue-collar workers. In clinical characteristics, advanced-stage cancer and experienced cancer recurrence was associated with leave of absence and discontinued working. In work-related and psychological factors, stress due to insufficient job control (relative risk ratio [RRR] = 2.26), interpersonal conflict (RRR = 1.86), job insecurity (RRR = 2.63), organizational system (RRR = 3.49), and lack of reward (RRR = 11.76), and less meaning to work were more likely to discontinue working after a cancer diagnosis. CONCLUSION: Occupational health care professionals and other stakeholders need to openly communicate with patients with cancer about potential barriers during the return-to-work trajectory.

A preoperative risk prediction model for high malignancy potential gastrointestinal stromal tumors of the stomach.

BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) exhibit various degrees of aggression and malignant potential. However, no systematic preoperative evaluation strategy to predict the malignancy potential of gastric GISTs has yet been developed. This study aimed to develop a reliable and easy-to-use preoperative risk-scoring model for predicting high malignancy potential (HMP) gastric GISTs. METHODS: The data of 542 patients with pathologically confirmed gastric GISTs who underwent resection were reviewed. Multivariate logistic regression analysis was used to identify significant predictors of HMP. The risk-scoring system (RSS) was based on the predictive factors for HMP, and its performance was validated using a split-sample approach. RESULTS: A total of 239 of 542 (44.1%) surgically resected gastric GISTs had HMP. Multivariate analysis demonstrated that tumor size, location, and surface changes were independent risk factors for HMP. Based on the accordant regression coefficients, the presence of surface ulceration was assigned 1 point. Tumor sizes of 4-6 cm and > 6 cm were assigned 2 and 5 points, respectively. Two points were assigned to cardia or fundus locations. A score of 3 points was the optimal cut-off value for HMP prediction. HMP were found in 19.8% and 82.7% of the low and high-risk groups of the RSS, respectively. The area under the receiver-operating characteristic curve for predicting HMP was 0.81 (95% confidence interval (CI) 0.75-0.86). Discrimination was good after validation (0.75, 95% CI 0.69-0.81). CONCLUSION: This simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment.

Adjuvant Chemotherapy vs. Surgery Alone for pT3N0M0 Gastric Cancer.

BACKGROUND: As both the role and clinical application of adjuvant chemotherapy (CTx) for pT3N0M0 gastric cancer after curative gastrectomy have fluctuated chronologically, the oncological benefit of adjuvant CTx in patients should be elucidated. METHODS: Between 2000 and 2018, 1083 patients underwent radical gastrectomy for pT3N0M0 gastric cancer and were subsequently divided into two groups: the surgery-alone group (n = 471) and the adjuvant CTx group (n = 612). Chronological changes in adjuvant CTx and various chemotherapeutic regimens were evaluated and disease-free survival was compared between the two groups. Risk factors for tumor recurrence were also analyzed. RESULTS: The proportion of patients in the surgery-alone group was more than 60% until 2001, whereas in the CTx group this increased to over 80%, especially after publication of the American Joint Committee on Cancer (AJCC) 7th edition staging manual. The main chemotherapeutic agents were tegafur-uracil (UFT) and 5-fluorouracil with leucovorin until 2008, whereas tegafur/gimeracil/oteracil (TS-1) has been the main agent since 2009. The 5-year disease-free survival was 89.2% in the surgery-alone group and 89.9% in the CTx group, which was not significantly different (p = 0.694). In multivariate analysis, larger tumor size (≥ 4.5 cm) and venous invasion were significant risk factors for tumor recurrence. In addition, adjuvant CTx did not improve the oncological outcome, even in the large tumor size group (p = 0.760) and the venous invasion group (p = 0.753). CONCLUSIONS: As adjuvant CTx did not show any oncological benefit in pT3N0M0 gastric cancer in this large-scale study, it might be unnecessary for these patients after curative gastrectomy.

Microsatellite Instability and Effectiveness of Adjuvant Treatment in pT1N1 Gastric Cancer: A Multicohort Study.

BACKGROUND: Microsatellite status is a prognostic biomarker in advanced gastric cancer. This retrospective study aimed to investigate the usefulness of microsatellite status in predicting prognosis and response to adjuvant treatment in pT1N1 gastric cancer. PATIENTS AND METHODS: Among 875 patients who underwent radical gastrectomy for pT1N1 gastric cancer at two tertiary hospitals, 838 with available microsatellite instability (MSI) data were included and classified into two groups according to microsatellite status: microsatellite stable (MSS) and MSI-high (MSI-H). Recurrence-free survival rate and risk factors for tumor recurrence were analyzed. RESULTS: Of 838 gastric cancer patients, 100 (11.9%) were MSI-H and 307 (36.6%) received adjuvant treatment. During median follow-up of 70 months, 42 (5.0%) patients experienced gastric cancer recurrence; hematogenous recurrences were the most common (45.2%). Recurrence-free survival was similar in the MSS and MSI-H groups (p = 0.27), and adjuvant treatment did not show an oncological benefit over surgery alone for pT1N1 gastric cancer (p = 0.53). On univariate analysis, age, operation period, and Lauren classification were significantly associated with tumor recurrence, while adjuvant treatment and MSI status were not associated with tumor recurrence. On multivariate analysis, MSI status was not associated with tumor recurrence, and adjuvant treatment worsened the tumor recurrence risk [hazard ratio (HR) 2.373, 95% confidence interval (CI) 1.125-5.006, p = 0.023). CONCLUSION: MSI status may not be a prognostic factor for tumor recurrence or a predictor of response to adjuvant treatment in pT1N1 gastric cancer patients. Considering that the effect of adjuvant treatment to decrease the risk of tumor recurrence is not clear, it may not be indicated in pT1N1 patients.

Association between cancer stigma and job loss among cancer survivors.

OBJECTIVE: Previous qualitative studies found cancer stigma was associated with work discrimination and job loss among cancer patients. This study aims to quantify the association between cancer stigma and job loss among cancer survivors. METHODS: For this study, we used the data from a face-to-face cross sectional survey conducted at two cancer hospitals in Seoul and Hwasun in South Korea from October 2017 to March 2018. Cancer stigma was assessed using a validated questionnaire which consists of 12 items in three domains: (a) impossibility of recovery; (b) stereotypes; and (c) discrimination. Multivariable logistic regression was performed to evaluate the association between cancer stigma and job loss adjusting age, sex, marital status, education, job type, residence area, cancer site, stage, comorbidity, time since diagnosis, and self-efficacy. RESULTS: Among 433 cancer survivors, 24.0% lost their jobs after cancer, and 20.7% experienced discrimination at work. Of total, 21.7% of the survivors agreed that it was difficult to treat cancer regardless of highly developed medical science. Survivors with stigma on impossibility of recovery and stereotypes were 3.10 (95% confidence interval [CI]: [1.76, 5.44]) and 2.10 (95% CI: [1.20, 3.67]) times more likely to lose a job than survivors without cancer stigma. Survivors with discrimination experience at work had 1.98 (95% CI: [1.05, 3.74]) times higher risk of losing a job than survivors without it. CONCLUSIONS: Survivors with cancer stigma were more likely to lose their jobs than survivors without cancer stigma. Considering its social and economic impact on job loss, comprehensive interventions for working cancer survivors as well as public campaigns against cancer stigma would be necessary.

Single patient classifier as a prognostic biomarker in pT1N1 gastric cancer: Results from two large Korean cohorts.

OBJECTIVE: Benefits of adjuvant treatment in pT1N1 gastric cancer (GC) remain controversial. Additionally, an effective biomarker for early GC is the need of the hour. The prognostic and predictive roles of single patient classifier (SPC) were validated in stage II/III GC. In this study, we aimed to elucidate the role of SPC as a biomarker for pT1N1 GC. METHODS: The present retrospective biomarker study (NCT03485105) enrolled patients treated for pT1N1 GC between 1996 and 2012 from two large hospitals (the Y cohort and S cohort). For SPC, mRNA expression of four classifier genes (GZMB, WARS, SFRP4 and CDX1) were evaluated by real-time reverse transcription-polymerase chain reaction assay. The SPC was revised targeting pT1 stages and the prognosis was stratified as high- and low-risk group by the expression of SFRP4, a representative epithelial-mesenchymal transition marker. RESULTS: SPC was evaluated in 875 patients (n=391 and 484 in the Y and S cohorts, respectively). Among 864 patients whose SPC result was available, 41 (4.7%) patients experience GC recurrence. According to revised SPC, 254 (29.4%) patients were classified as high risk [123 (31.5%) and 131 (27.1%) in the Y and S cohorts, respectively]. The high risk was related to frequent recurrence in both Y and S cohort (log-rank P=0.023, P<0.001, respectively), while there was no difference byGZMB and WARS expression. Multivariable analyses of the overall-cohort confirmed the high risk of revised SPC as a significant prognostic factor [hazard ratio (HR): 4.402 (2.293-8.449), P<0.001] of GC. A significant difference was not detected by SPC in the prognosis of patients in the presence and absence of adjuvant treatment (log-rank P=0.670). CONCLUSIONS: The present study revealed the revised SPC as a prognostic biomarker of pT1N1 GC and suggested the use of the revised SPC for early-stage GC as like stage II/III.

Nomogram to predict lymph node metastasis in patients with early gastric cancer: a useful clinical tool to reduce gastrectomy after endoscopic resection.

BACKGROUND: The indications for endoscopic dissection have been expanded to improve the quality of life of patients with early gastric cancer (EGC). This study aimed to develop a nomogram to predict the status of lymph node metastasis with the aim of avoiding unnecessary gastrectomies. METHODS: We reviewed the clinicopathological data of 10 579 patients who underwent curative resection for EGC. The nomogram was developed by multivariate analysis and was evaluated by external validation. Overall, disease-free and recurrence-free survival were compared between the gastrectomy group of 6641 patients and the endoscopic dissection group of 999 patients to show the efficacy of the nomogram. RESULTS: Multivariate analyses revealed that age, tumor size, lymphatic invasion, depth of invasion, and histologic differentiation were all significant prognostic factors for lymph node metastasis. The nomogram had good discriminatory performance, with a concordance index of 0.846. This was supported by the external validation point of 0.813. For patients with low risk of lymph node metastasis on the nomogram (≤ 3 % of the provisional value in this study), the endoscopic dissection and gastrectomy groups had comparable rates of overall (P = 0.32), disease-free (P = 0.47), and recurrence-free (P = 0.09) survival. CONCLUSIONS: We developed and validated a nomogram that predicts the risk of lymph node metastasis in EGC based on a large database. This precision nomogram is useful to avoid unnecessary gastrectomy after endoscopic dissection, which may ultimately improve the quality of life of patients with EGC.

Gastric cancer: development and validation of a CT-based model to predict peritoneal metastasis.

BACKGROUND: The sensitivity of computed tomography (CT) for the detection of peritoneal metastasis (PM) of advanced gastric cancer (AGC) is relatively low. PURPOSE: To develop a predictive model to improve the sensitivity of PM detection and to externally validate this model. MATERIAL AND METHODS: We analyzed data from 78 patients with PM, who had undergone preoperative CT and subsequent surgery between January 2012 and December 2014, and 101 controls to form a derivation set, retrospectively. The following CT findings were evaluated: tumor size; Bormann type 4; enlarged lymph node; indirect findings of PM (peritoneal thickening, fat stranding, plaques or nodules on the peritoneum, and ascites); and definitive findings of PM (omental cake and rectal shelf). A predictive model was created using multivariate logistic regression. Receiver operating characteristic (ROC) analyses were performed to assess the diagnostic performance of the model. The accuracy was externally validated at other hospitals on 31 patients with PM and 48 patients without PM. RESULTS: Tumor size >5.2 cm, Bormann type 4, enlarged lymph node, peritoneal plaques or nodules, and ascites were independently associated with PM. It was able to predict PM with a higher area under the ROC curve (AUC) and sensitivity than definitive findings of PM (AUC 0.903 vs. 0.647, sensitivity 92.3% vs. 38.3%). External validation confirmed the predictive power with good inter-observer agreement. CONCLUSION: The CT-driven model shows higher AUC and sensitivity for prediction of PM and may help decision-making with the aim of improving care for patients with AGC.

Bridging genomics and phenomics of gastric carcinoma.

Genetic alterations are the starting point leading to numerous changes in clinical and pathologic features (phenotypes) of individual cancers; however, their inter-relationships in gastric cancers (GC) are unclear. We performed massive parallel sequencing of 381 cancer-related genes and compared the results with clinical and pathologic findings in 330 GC. High tumor mutation burden (TMB) accounted for 11% of GC (n = 37) and all 19 MSI-H GCs were high TMB. High TMB was significantly more frequent in intestinal-type by Lauren, tumor with higher host cellular immune response, earlier AJCC stage and favorable prognosis. The most significantly mutated genes were TP53 (54%), ARID1A (23%), CDH1 (22%), PIK3CA (12%), RNF43 (10%) and KRAS (9%). For receptor tyrosine kinases, amplifications detected by immunohistochemistry were higher than sequencing (HER2, 9.1% vs. 5.8%; EGFR, 11.2% vs. 6.1%; FGFR2, 4.6% vs. 3.9%, c-MET, 3.4% vs. 0.9%). PTEN protein loss (22%) correlated well with underlying PTEN alterations while ATM loss (27%) was not significantly correlated with genetic alterations of ATM. p53 protein expression predicted alterations of TP53 with high sensitivity (97.8%) and low (15.9%) specificity. The poorly cohesive histology/CDH1-mutant GC subgroup showed the worst survival (p < 0.001). PD-L1 expression was significantly associated with MSI-H, MLH1 loss, ATM loss, MET positivity, higher host immune response, and genetic alterations of ARID1A, BRD3, PIK3CA, KRAS, MAP3K13, CDH2, PTEN and ESR1. The merged clinical, pathology and genomics of GC provide a better understanding of GC and new insights into the treatment of GC.

Prognostic Impact of Microsatellite Instability in Asian Gastric Cancer Patients Enrolled in the ARTIST Trial.

BACKGROUND: Caucasian patients with microsatellite instability (MSI)-high gastric cancer (GC) may have better prognosis but worse outcomes. OBJECTIVE: Here we explored the prognostic role of MSI in Asian patients. METHODS: This post hoc analysis comprehended radically resected GC patients randomized to XP (capecitabine/cisplatin) or XPRT. MSI status was assessed by combining immunohistochemistry with multiplex polymerase chain reaction. The MSI prognostic effect on disease-free survival (DFS) and overall survival (OS) was evaluated. RESULTS: 393 tissue samples were analyzed and 35 (9%) were MSI-high. This subgroup was characterized by: older age, Borrmann classification 1-2, antral localization, T3-4 stage, and intestinal type. At univariable analysis, the microsatellite-stable subgroup showed a trend toward a worse prognosis as compared to the MSI-high group: 3-year DFS was 76.3 versus 85.4% (p = 0.122); 3-year OS was 81.7 versus 91.4% (p = 0.046). Multivariable analyses confirmed it in both DFS (hazard ratio, HR = 2.32 [95% CI 0.91, 5.88]; p = 0.077) and OS (HR = 3.17 [95% CI 0.97, 10.43]; p = 0.057). CONCLUSIONS: MSI-high status was associated with specific clinical-pathological features and a trend toward better outcomes of Asian GC patients.

Effect of Tailored Perigastric Lymph Node Dissection on Gastric Motility in a Canine Model.

BACKGROUND: Combination laparoscopic lymph node (LN) dissection and endoscopic resection is a promising treatment for early gastric cancer. However, LN dissection could cause nerve injury and deterioration of motility in the preserved stomach. This experimental study aims to evaluate changes in gastric motility after tailored perigastric regional lymph node dissection without gastrectomy. MATERIALS AND METHODS: We identified four most frequently involved LN combinations considering tumor location from retrospective reviews of 4697 gastrectomy patients. We randomly assigned 55 dogs to five groups: control (laparotomy only) and four experimental groups with LN dissection without gastrectomy: group 1 (LNs 3, 7, and 8), group 2 (LNs 3, 4, and 6), group 3 (LNs 1, 3, and 7), and group 4 (LNs 3, 4, and 11). Gastric emptying time (GET) was measured using barium-impregnated polyethylene spheres. GET50 and GET75 were the time points when 50% and 75% of the markers, respectively, had emptied from the stomach. RESULTS: On postoperative days (PODs) 2 and 3, GET50, GET75, and proportion of GET50 <4 h in groups 1 and 2 were comparable with controls. However, group 3 showed delayed GET50 and GET75, and groups 3 and 4 demonstrated significantly smaller proportions of GET50 <4 h compared with controls on PODs 2 and 3. This effect resolved by POD 6 and there were no significant differences in GET50, GET75, or proportion of GET50 <4 h between the groups. CONCLUSIONS: Tailored perigastric LN resection without gastrectomy was feasible and acceptable in terms of postoperative motility in the preserved stomach.

Prognostic Impact of Increased Perioperative Platelet Count in Gastric Cancer Patients.

BACKGROUND: Solid tumors are a common cause of secondary (reactive) thrombocytosis, a paraneoplastic syndrome that is also a prognostic factor for various cancers. However, cutoff values for platelet count specific to gastric cancer and their prognostic roles are unknown. METHODS: We retrospectively analyzed records of 4643 patients with gastric cancer who underwent radical surgery from 2007 to 2010. The minimum P-value approach was used with the log-rank test to determine the optimal prognosis predicting threshold for preoperative platelet count. Change in perioperative platelet count over time was evaluated with a generalized estimating equation. Clinicopathologic features and prognostic significance were analyzed according to platelet count. RESULTS: Thrombocytosis prevalence (platelet count ≥40 × 104/µL) was 1.6% (75 of 4643 patients). The platelet count cutoff value with the lowest P-value was ≥25.5 × 104/µL, and patients with higher platelet count had more advanced disease. Multivariate analysis showed that cutoff value was an independent prognostic factor of overall survival (hazard ratio 1.19, 95% confidence interval 1.03-1.37, P = 0.017). Patients who underwent adjuvant chemotherapy (n = 1300) and had a greater than 10% increase in platelet count at postoperative 1 y compared to before surgery had significantly poorer overall survival (hazard ratio 1.65, 95% confidence interval 1.11-2.45, P = 0.013). CONCLUSIONS: Elevated preoperative platelet count (≥25.5 × 104/µL) and increased platelet count (≥10%) at postoperative 1 y in an adjuvant chemotherapy group were unfavorable prognostic factors. Platelet count could be a cost-effective biomarker for screening and monitoring patients with unfavorable survival outcomes.

A prediction model for lymph node metastasis in early-stage gastric cancer: Toward tailored lymphadenectomy.

BACKGROUND: The aim of this study was to develop a prediction model for the presence and location of lymph node metastasis (LNM) in early gastric cancer. METHOD: We reviewed medical records of 4 929 patients who underwent radical gastrectomy for early gastric cancer. Variables of age, sex, lymphatic invasion, depth of invasion, location, gross type, differentiation, and tumor size were analyzed. Logistic regression analysis was used to determine independent predictors of LNM at each LN station. RESULT: Overall incidence of LNM was 9.1% (448/4 929 patients). For the presence of LNM, risk factors of age, sex, lymphatic invasion, depth of invasion, anatomical part, gross ulceration, size, and tumor differentiation were significantly associated with LNM. The area under the curve (AUC) for predicting LNM after validation was 0.834 for the test set. For the location of LNM, age, sex, lymphatic invasion, depth of invasion, anatomical part, circumferential portion, gross type, differentiation, and tumor size were significantly associated with LNM. The AUC of each LN station was favorable with the test set. CONCLUSION: Predicting the location of metastatic LNs appeared to be possible in patients with early gastric cancer.

A comparison of short-term postoperative outcomes including nutritional status between gastrectomy with simultaneous cholecystectomy and gastrectomy only in patients with gastric cancer.

OBJECTIVE: We aimed to evaluate the effect of simultaneous cholecystectomy on the short-term postoperative outcomes and nutritional status in patients with gastric cancer. METHODS: We retrospectively reviewed data from 4,820 patients with gastric cancer who underwent gastrectomy from January 2011 to December 2016. Patients who underwent only gastrectomy (N=4,578) were matched to those who underwent simultaneous cholecystectomy during gastrectomy (N=242) at a 1:1 ratio using propensity score matching analysis. The nutritional status and inflammatory responses preoperatively and postoperatively and postoperative outcomes were compared between the groups. RESULTS: The simultaneous cholecystectomy group showed more intraoperative blood loss and a longer operative time than the gastrectomy only group [150.0 (100.0, 200.0) mL vs. 100.0 (100.0, 200.0) mL, P=0.006; 176.0 (150.0, 210.0) min vs. 155.0 (128.0, 188.0) min, P<0.001, respectively]. Intraoperative event rate, postoperative complication rate, and postoperative recovery did not differ between the groups. All parameters including body weight, the hemoglobin level, absolute lymphocyte count, total protein level, albumin level, fasting glucose level, and prognostic nutritional index excluding the cholesterol level were not significantly different between the groups, and their changing patterns were similar. Although the cholesterol level was significantly lower in the simultaneous cholecystectomy group than in the gastrectomy only group at all follow-up points, the mean value of the decreased cholesterol level was within normal range. CONCLUSIONS: In gastric cancer patients with gallbladder disease, simultaneous cholecystectomy is safe and not associated with additional nutritional loss.

Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.

BACKGROUND: Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS: Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS: We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72-0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80-0.93). CONCLUSIONS: We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.

Adjuvant Chemotherapy Versus Chemoradiotherapy Versus Surgery Alone for Early Gastric Cancer with One or Two Lymph Node Metastasis.

BACKGROUND: Limited studies exist comparing clinical outcomes by adjuvant treatment for pT1N1 gastric cancer. This study compared the disease-free survival (DFS) of patients with pT1N1 gastric cancer according to the type of adjuvant treatment-surgery alone, chemotherapy (CTx), and chemoradiotherapy (CCRTx)-and evaluated risk factors for tumor recurrence. METHODS: Between 1995 and 2015, 738 patients underwent radical gastrectomy for pT1N1 gastric cancer and were divided into three groups: surgery alone (n = 355), CTx (n = 214), and CCRTx (n = 169). Chronological changes in adjuvant treatment type and chemotherapeutic regimens were evaluated and DFS was compared. Risk factors for tumor recurrence were analyzed. RESULTS: The proportion of patients who underwent surgery alone was more than 50% until 2001, and the proportion of those who had either CTx or CCRTx was more than 50% from 2002 to 2011, after which the proportion who underwent surgery alone increased again. The main chemotherapeutic agent was 5-fluorouracil with leucovorin. The 5-year DFS was 96.5% in the surgery-alone group, 96.0% in the CTx group, and 95.8% in the CCRTx group (no significant difference). The various chemotherapeutic regimens did not show differences in DFS. In univariate and multivariate analyses, adjuvant CTx and CCRTx showed no beneficial effect with regard to tumor recurrence. CONCLUSIONS: Because adjuvant CTx and CCRTx did not show any benefit with regard to tumor recurrence, these treatment strategies might be unnecessary for pT1N1 gastric cancer after gastrectomy. Further studies are necessary to reveal pT1N1 gastric cancer patient subgroups who might benefit from adjuvant treatments.

Prediction of Overall Survival and Novel Classification of Patients with Gastric Cancer Using the Survival Recurrent Network.

BACKGROUND: Artificial neural networks (ANNs) have been applied to many prediction and classification problems, and could also be used to develop a prediction model of survival outcomes for cancer patients. OBJECTIVE: The aim of this study is to develop a prediction model of survival outcomes for patients with gastric cancer using an ANN. METHODS: This study enrolled 1243 patients with stage IIA-IV gastric cancer who underwent D2 gastrectomy from January 2007 to June 2010. We used a recurrent neural network (RNN) to make the survival recurrent network (SRN), and patients were randomly sorted into a training set (80%) and a test set (20%). Fivefold cross-validation was performed with the training set, and the optimized model was evaluated with the test set. Receiver operating characteristic (ROC) curves and area under the curves (AUCs) were evaluated, and we compared the survival curves of the American Joint Committee on Cancer (AJCC) 8th stage groups with those of the groups classified by the SRN-predicted survival probability. RESULTS: The test data showed that the ROC AUC of the SRN was 0.81 at the fifth year. The SRN-predicted survival corresponded closely with the actual survival in the calibration curve, and the survival outcome could be more discriminately classified by using the SRN than by using the AJCC staging system. CONCLUSION: SRN was a more powerful tool for predicting the survival rates of gastric cancer patients than conventional TNM staging, and may also provide a more flexible and expandable method when compared with fixed prediction models such as nomograms.

Factors Associated With Host Immune Response and Number of Lymph Nodes: A Large Retrospective Cohort Study.

BACKGROUND: The host immune response (HIR) against tumor cells is one of the key players in antitumor activities. However, the relationship between HIR and regional lymph nodes (LN) and their impacts on prognosis have not been studied. METHODS: This study analyzed HIR and clinicopathologic factors for 8819 consecutive gastric cancer patients who underwent gastrectomy and D2 LN dissection. The findings confirmed Epstein-Barr virus (EBV) with Epstein-Barr encoding region in situ hybridization, HIR grading (G1, G2, and G3), LN numbers classified into seven groups, and performed ordinal regression analysis. RESULTS: The mean number of LNs was 41. A higher degree of HIR was significantly associated with male sex, EBV+, non-intestinal histology by Lauren classification, earlier American Joint Committee on Cancer (AJCC) stage, and greater number of LNs (P < 0.001). Female gender, younger age (< 60 years), EBV+, non-intestinal histology, higher HIR grade (G2 and G3), larger tumor size, and deeper invasion depth were significantly related to a higher number of LNs, with an odds ratio greater than 1. In cancer-specific survival analyses, EBV+, younger age, higher HIR grade (G3), and increased number of LNs were independent prognostic factors in addition to AJCC stage. CONCLUSIONS: The HIR was associated with increased number of LNs was a significant favorable prognosticator.

Lymphovascular invasion and lymph node metastasis rates in papillary adenocarcinoma of the stomach: implications for endoscopic resection.

BACKGROUND: Current Japanese gastric cancer treatment guidelines recommend the same endoscopic resection criteria for papillary early gastric cancer (EGC) and well-differentiated (WD) or moderately differentiated (MD) EGC. To evaluate the appropriateness of this recommendation, we compared the clinicopathological characteristics of papillary EGC with those of WD, MD, poorly differentiated (PD), and signet ring cell (SRC) EGC. METHODS: A total of 6710 patients who underwent radical gastrectomy for EGC were included. Clinicopathological characteristics of papillary EGC were retrospectively reviewed and compared with those in other EGC subtypes. RESULTS: Papillary EGC accounted for 1.9% (130/6710) of total cases. Patients with papillary EGC were older and showed a male predominance compared to patients with PD or SRC EGC. Papillary EGCs showed significantly higher submucosal and lymphovascular invasion rates than WD or MD EGC or PD or SRC EGC. However, the LN metastasis rate of papillary EGC was comparable to or lower than that in other EGC subtypes. LN metastasis rates in mucosal cancers were 1.5%, 1.1%, and 4.0%, and those in submucosal cancers were 9.4%, 11.9%, and 17.6% for papillary EGC, WD or MD EGC, and PD or SRC EGC, respectively. In multivariate analysis, lymphatic invasion and PD or SRC histology were the strongest risk factors for LN metastasis. Among 63 papillary EGC that met the curative endoscopic resection criteria, no case showed LN metastasis. CONCLUSIONS: Endoscopic resection can be indicated for papillary EGC according to current guidelines. Given a considerable lymphovascular invasion rate, careful histological evaluation is required after endoscopic resection for papillary EGC.