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.

Associations of patient-generated subjective global assessment (PG-SGA) and NUTRISCORE with survival in gastric cancer patients: timing matters, a retrospective cohort study.

BACKGROUND: The timing of nutritional assessment may be important to treat cancer patients and predict their prognosis. This study examined whether Patient-Generated Subjective Global Assessment (PG-SGA) and NUTRISCORE scores were associated with survival among gastric cancer patients who underwent surgery and chemotherapy and whether the timing of the assessment after surgery mattered. METHODS: A total of 952 gastric cancer patients (622 men and 330 women) were included in this retrospective cohort study. The PG-SGA and NUTRISCORE scores were calculated at 1 month (n = 952), 2 months (n = 657), and 3 months (n = 294) after surgery. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The PG-SGA scores assessed at 1 month after gastrectomy were not associated with survival. However, high PG-SGA scores at 2 months after gastrectomy (median = 65 days) were associated with an increased risk of mortality; the HR (95% CI) was 2.26 (1.22-4.21) for 9-11 vs. ≤ 5 of PG-SGA scores. When we included patients who received all three consecutive consultations, HR (95% CI) was 2.56 (1.02-6.42) for ≥ 9 (malnutrition) vs. ≤ 8 of PG-SGA scores assessed at 3 months after surgery (median days = 98 days). Likewise, high NUTRISCORE scores assessed at the 3-month follow-up were associated with higher mortality; the HR (95% CI) was 3.84 (1.18-12.55) for ≥ 7 vs. ≤ 4 of NUTRISCORE scores. CONCLUSION: Malnutrition assessed with the PG-SGA and NUTRISCORE at 2 to 3 months after gastrectomy was associated with poor survival among gastric cancer patients. Our findings suggest that the timing of the nutritional evaluation may be important in identifying and treating malnutrition related to gastric cancer prognosis.

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.

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.

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.

Oncological safety of use of ultrasonic activated shears in gastric cancer surgery: Long-term results of randomized controlled trial.

OBJECTIVE: Ultrasonically activated shears (UAS) have been applied in open gastric surgeries with no or little evidence. It was previously reported about the surgical outcome and effectiveness of UAS based on a randomized controlled trial of 256 patients with gastric cancer. We aimed to clarify the long-term oncological safety of the use of UAS in the aspect of overall survival and recurrence. METHODS: Gastric cancer patients who underwent gastrectomy with D2 lymph node dissection were enrolled and randomly assigned to either the conventional surgery group (n=125) or the UAS group (n=128). Survival, recurrence and long-term postoperative complications were compared between the two groups. The median follow-up period was 56 months. RESULTS: Gastric cancer-related death was higher in patients of the UAS group compared with the conventional group (P=0.019). Overall survival rates stratified by stage were not significantly different between the two groups (P=0.170). Disease-free survival rates stratified by stage and recurrence-free survival rates of gastric cancer were similar between the conventional group and the UAS group (P=0.313 and 0.199, respectively). The postoperative complication rate was not significantly different between the groups (P=1.000). CONCLUSIONS: It is suggested that the use of UAS in gastrectomy for gastric cancer showed oncologically acceptable safety compared with conventional electric instruments even in long-term period.

Effect of Intravenous Ferric Carboxymaltose on Hemoglobin Response Among Patients With Acute Isovolemic Anemia Following Gastrectomy: The FAIRY Randomized Clinical Trial.

IMPORTANCE: Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. OBJECTIVE: To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. DESIGN, SETTING, AND PARTICIPANTS: The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. INTERVENTIONS: Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). MAIN OUTCOMES AND MEASURES: The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. RESULTS: Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. CONCLUSION AND RELEVANCE: Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01725789.

The risk of lymph node metastases in 3951 surgically resected mucosal gastric cancers: implications for endoscopic resection.

BACKGROUND AND AIMS: Endoscopic resection for mucosal gastric cancer (MGC) is highly recommended in the absence of lymph node metastasis (LNM). We aimed to clarify the risk factors for LNM in MGC and to investigate the association of LNM with the indication criteria for endoscopic submucosal dissection (ESD). METHODS: A retrospective cohort study was performed on 3951 patients with MGC who underwent radical gastrectomy at the Samsung Medical Center in Seoul, Republic of Korea, between September 1994 and September 2010. RESULTS: Of the patients with MGC, 101 (2.60%) were positive for LNM. Multivariate analysis, followed by univariate analysis, revealed the following risk factors for LNM in MGC: large tumor size, undifferentiated tumor type, lymphatic invasion, perineural invasion, and associated ulceration in the tumor (hazard ratio 1.25, 7.49, 20.65, 23.45, and 4.07, respectively). Patients without LNM had significantly increased survival and/or recurrence-free survival rates than patients with LNM (188.4/209.8 months vs 169.5/188.0 months; P = .029/.004, respectively). Only 3 of 1065 patients (0.3%) who met the absolute indication criteria for ESD had LNM. Of those who met the expanded indication criteria for ESD, 11 of 2678 patients (0.4%) had LNM. LNM also was found in 2 patients who had a differentiated tumor <0.5 cm without ulceration. CONCLUSION: The risk for LNM was very low when patients with MGC met the absolute and/or expanded criteria for endoscopic resection, which meant the indication criteria for ESD was safe and acceptable. However, although the risk for LNM is very low, it should not be considered negligible in endoscopic resection.

HER2-positive gastric cancer with concomitant MET and/or EGFR overexpression: a distinct subset of patients for dual inhibition therapy.

Growth factor receptors, often carrying tyrosine kinase activities in their cytoplasmic domains, are overexpressed in many cancers. Coactivation of receptor tyrosine kinases (RTKs) plays a critical role in tumor response to targeted therapeutics. We examined concomitant overexpression of EGFR and MET in patients with HER2(+) and HER2(-) gastric cancers (GCs). Tissue microarray samples obtained from 1,589 GC patients who received R0 gastrectomy with extensive node dissection and adjuvant chemoradiationtherapy were analyzed by immunohistochemistry and fluorescence in situ hybridization. HER2(+) was observed in 169 patients (11%). Out of 169 HER2(+) patients, 15 (9%) were EGFR(+) and MET(+) , 29 (17%) were EGFR(+) , 37 (22%) were MET(+) and the remaining 88 patients (52%) were HER2(+) only, without concomitant EGFR or MET overexpression. Greater number of overexpressed RTKs correlated with younger age (p < 0.001), larger tumor size (p = 0.027), intestinal histology (p < 0.001) and shorter overall survival (p = 0.002). The mean overall survival was 113 months for HER2(-) /EGFR(-) /MET(-) and 63 months for HER2(+) /EGFR(+) /MET(+) subgroups. Patients with HER2(+) /EGFR(+) /MET(+) GCs had a substantial risk of death with a hazard ratio of 3.01 (95% CI: 1.54-5.90), compared with HER2(-) /EGFR(-) /MET(-) GC patients. Using patient-derived tumor cell models isolated from pericardial effusion of HER2(+) and MET(+) GC cases, we demonstrated that the combination of HER2-inhibitor (lapatinib) and MET-inhibitor offered a more profound inhibition in the ERK/AKT pathway and cell proliferation than lapatinib alone. Co-overexpression of RTKs was demonstrated in small subsets of GC associated with aggressive behavior and in these cases, combination therapy may be considered as potential treatment options.

Techniques of reduced PRT laparoscopy-assisted distal gastrectomy (duet LADG).

BACKGROUND: Reduced-port laparoscopic surgery for patients with early gastric cancer has been rarely reported. The aim of this study was to introduce techniques of the reduced-port laparoscopy-assisted distal gastrectomy (duet LADG) in patients with early gastric cancer. METHODS: Duet LADG was performed by two persons, an operator and a scopist. Three 10 mm ports were used on the umbilicus and both sides of the lower abdomen. The same laparoscopic instruments were used for duet LADG as for conventional LADG. After the liver was retracted with a 1-0 nylon suture, partial omentectomy with D1 + ß or more lymph node dissection was made. After distal subtotal resection of the stomach, bowel continuity was restored by intracorporeal gastrojejunostomy using two linear staplers. A specimen was removed through the umbilical incision after the extension. RESULTS: A total of 30 consecutive patients underwent duet LADG from October to December 2013. The median age of the patients was 51 years (range 29-75 years), and their median body mass index was 23.2 kg/m(2) (range 18.5-29.6 kg/m(2)). Sixteen (53.3%) of 30 patients were female. Operating times for patients who received duet LADG were 121.2 ± 17.7 min. Blood loss during operations averaged 82 ml. The median number of dissected lymph nodes was 35 (range 24-66). There was no patient with fewer than 15 dissected lymph nodes. The rate of complications in patients who underwent duet LADG was 16.7% (5 of 30 patients). Two patients (6.7%) experienced ileus, and another 2 (6.7 %) patients experienced small bowel obstruction. One patient had pneumonia. There was no postoperative mortality. CONCLUSIONS: Duet LADG for patients with early gastric cancer is feasible without the need for additional ports, any special devices, or an assistant.

Lymphoepithelioma-like carcinoma: a distinct type of gastric cancer.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare type of gastric carcinoma and has histologic features of intense lymphocytic infiltration. In this study, we attempted to analyze the clinicopathologic characteristics and survival outcome of patients with LELC compared with those with non-lymphoepithelioma-like carcinoma (NLELC). METHODS: We studied 4282 patients who underwent gastrectomies to treat gastric cancer at the Department of Surgery of the Samsung Medical Center in Seoul, between January 2008 and December 2010. The clinicopathologic features and clinical outcomes of patients with LELC (n = 46) were compared with those with NLELC (n = 4236). In situ hybridization for Epstein-Barr virus (EBV) positivity was performed on the tissue of patients with LELC (n = 46) and NLELC (n = 1247). RESULTS: The patients with LELC are male predominant and had more upper locations, more indeterminate Lauren classifications, lower T stages, less lymphatic invasion, and more positive EBV in situ hybridization compared with those of the NLELC group (80.4% versus 6.5%). Age, histologic type, Lauren type, the location of the tumor, the depth of the invasion, lymph node metastasis, and venous invasion were independent prognostic factors; however, the LELC type itself was not predictive of outcome. The 5-y survival rate of the LELC group (97.7%) was better than that of the NLELC group (89.4%); however, this difference was not statistically significant (P = 0.127). CONCLUSIONS: The results of our study suggest that LELC is a less advanced disease than NLELC in terms of depth of invasion and lymphatic invasion at diagnosis. However, our study does not examine LELC as an independent prognostic factor of gastric cancer. Further studies are needed to explore its associations with EBV and a distinct pathway of carcinogenesis from NLELC.

CD151 overexpression is associated with poor prognosis in patients with pT3 gastric cancer.

INTRODUCTION: CD151, a transmembrane protein of the tetraspanin family, is implicated in the regulation of cell-substrate adhesion and cell migration. Overexpression of CD151 has been reported in several cancers and controls MET-dependent neoplastic growth by enhancing receptor signaling. However, association of CD151 overexpression with MET or tumor progression has not been reported in gastric cancer. MATERIALS AND METHODS: We conducted immunohistochemical analysis of CD151 overexpression in 491 pT3 gastric carcinomas and analyzed the relationship with MET overexpression and prognostic significance. RESULTS: CD151 was highly expressed in 119 gastric carcinomas (24.2 %) and was significantly associated with higher pN stages. Patients with CD151-positive gastric cancer showed shorter overall (p = 0.003) and disease-free survival (p = 0.001) compared with patients with CD151-negative gastric carcinoma. CD151 overexpression was an independent prognostic factor for overall survival [hazard ration (HR) 1.335; 95 % CI 1.005-1.775; p = 0.046] and disease-free survival (HR 1.903; 95 % CI 1.348-2.685; p < 0.001). Co-overexpression of CD151 and MET was observed in 30 (6.1 %) gastric cancers and was more frequent in advanced pN stages than in other groups. Moreover, co-overexpression of CD151 and MET was a strong independent prognostic factor for overall survival (HR 3.163; 95 % CI 1.958-5.108; p < 0.001) and disease-free survival (HR 3.834; 95 % CI 2.145-6.852; p < 0.001). CONCLUSION: CD151 overexpression is an independent prognostic factor and could be a potential molecular therapeutic target in patients with advanced gastric cancers. Further studies are needed to establish the biological significance of CD151/MET co-overexpression and the potential of targeting both molecules as a therapeutic strategy.

Ultrasonically activated shears versus electrocautery in open gastrectomy for gastric cancer: a randomized controlled trial.

BACKGROUND: Use of ultrasonically activated shears (UAS) is gaining popularity in open surgery but without concrete evidence. We conducted a prospectively randomized study to assess the efficacy of ultrasonic dissection in open gastrectomy for gastric cancer. METHODS: Patients with gastric cancer who were to undergo gastrectomy with D2 lymph node dissection were enrolled and assigned to either the conventional surgery group (n = 125) or the UAS group (n = 128). RESULTS: The mean operating time was significantly reduced in the UAS group (89.3 ± 15.6 min) when compared to the conventional group (97.8 ± 17.2 min; p < 0.001). However, we did not find any significant difference in operative blood loss, the amount of postoperative abdominal drainage, or the rate of postoperative complications between the groups. A multivariate analysis for operating time revealed that the use of UAS, female gender and BMI less than 25 were significantly associated with reduced operating time. The operating time was significantly longer in the conventional group than in the UAS group (B 7.786; 95 % CI 4.103-11.468; p < 0.001). In the subgroup analysis, the use of UAS significantly reduced the operating time, especially in male patients, regardless of the BMI status. CONCLUSIONS: The use of UAS in gastrectomy for gastric cancer was a safe and efficient method, especially in terms of reducing operating time for male patients.

MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas.

The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P<0.0001), increased copy number gain (r=0.393, P=0.000002) and amplification of MET gene. Moreover, patients with MET overexpression showed shorter overall survival (HR, 1.781; 95% CI, 1.324-2.395; P<0.001) and disease-free survival (HR, 1.765; 95% CI, 1.227-2.541; P=0.002) compared with patients without MET overexpression. However, membranous overexpression of MET did not highly correlate with mRNA level (r=0.274, P=0.002), copy number gain or survival (P>0.05). We developed highly correlating interpretation methods of MET immunohistochemistry in gastric carcinomas. MET overexpression is an independent prognostic factor and could be a potential target and predictor of benefit for targeted therapy with MET inhibitors.

Meso-jejunal lymph node dissection has a survival benefit in patients with remnant gastric cancer.

BACKGROUND: Clinical benefits of the meso-jejunal lymph node (MJLN) dissection in remnant gastric cancer (RGC) patients have not been fully established. Hence, in this retrospective study, we evaluated the survival benefit of MJLN dissection and prognostic significance of MJLN metastasis in RGC patients who underwent gastrojejunostomy reconstruction after their initial gastrectomy. METHODS: We retrospectively reviewed 391 patients who underwent surgery for RGC at our institution between 1996 and 2019. Among them, 60 patients had MJLN dissection. The index value of the survival benefit gained by dissection of the MJLN was calculated by multiplying the frequency of metastasis at the MJLN station and the 5-year overall survival rate (5YOS) of patients with metastasis at that station. When the metastatic rate or 5YOS exceeded 10%, dissection was recommended. An index value of dissection greater than 1.0 was considered significant. RESULTS: Total metastatic rate of MJLN was 35% (n = 21/60). Patients with MJLN metastasis had advanced pathologic stage compared to patients in the no-metastasis group (p < 0.001). In T2-T4 RGC patients, the metastatic rate of MJLN was 48.6% (n = 17/35), and their 5YOS was 28.4%. The calculated index value was 13.8. Also, patients with MJLN metastasis had a poorer overall survival than those without metastasis. MJLN metastasis was an independent prognostic factor of overall survival in multivariate analysis (HR 6.77, 95%CI 2.21-20.79, p = 0.001). CONCLUSION: MJLN dissection should be considered for advanced RGC patients who underwent gastrojejunostomy after distal gastrectomy during their initial surgery according to the index value.

Prognostic Significance of Esophagogastric Junction Invasion in Patients with Adenocarcinoma of the Cardia or Subcardia.

BACKGROUND: There has been no comparison of the prognoses of Korean patients who underwent curative surgery for cancer located at the cardia or subcardia of the stomach. We performed this comparison and further investigated the prognostic significance of esophagogastric junction (EGJ) invasion in patients. METHODS: The medical records of patients (n = 511) who were diagnosed with cardia or subcardia cancer and underwent surgery between January 2010 and May 2019 were retrospectively reviewed. Patients were further categorized into four groups for analysis: subcardia gastric cancer (sGC; subcardia cancer without EGJ invasion; n = 97), AEG (adenocarcinoma of the esophagogastric junction) type III (subcardia cancer with EGJ invasion, n = 54), AEG type II without EGJ invasion (n = 158), and AEG type II with EGJ invasion (n = 202). We compared the overall survival of the four groups using a gastric cancer staging system and evaluated the prognostic significance of EGJ invasion with multivariate analysis. RESULTS: The median follow-up of patients was 46.0 months (range: 0-124 months). There was significant difference in overall survival curves among the four groups (p < 0.001). Subgroup analysis showed a significant difference in overall survival between the groups with and without EGJ invasion (p < 0.001). Cancers with EGJ invasion were more frequently in the cardia (p < 0.001), had a larger size (p < 0.001), and showed a more advanced pathologic stage (stages II and III; 67.6% versus 33.7%, p < 0.001) than those without EGJ invasion. EGJ invasion and the pathologic stage were significant independent prognostic factors of overall survival in cardia and subcardia cancer patients (hazard ratio 2.24, 95% confidence interval 1.32-3.81, p = 0.003). CONCLUSION: The overall survival between patients with cardia or subcardia cancer was significantly different according to EGJ invasion. EGJ invasion was an independent prognostic factor and should be considered for staging. Additional research is needed to apply this feature to gastric and esophageal cancer classification.