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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. 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. 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 ( , , and ) and 2 miRNAs ( and ), 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). 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.

The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P  = 0.024) and wound complications (0.6% vs. 3.1%, P  = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P  < 0.001) than the open group (N = 318). The superiority of the laparoscopic approach was also demonstrated in patients with tumors larger than 5 cm, and at unfavorable locations. The recurrence-free survival was not different between the two groups, regardless of tumor size, locational favorableness, and risk classifications. Cox regression analysis revealed that tumor size larger than 5 cm, higher mitotic count, R1 resection, and tumor rupture during surgery were independent risk factors for recurrence. Laparoscopic surgery provides lower rates of complications and shorter hospitalizations for patients with gastric GIST than open surgery.

This phase II clinical trial was performed to determine whether reduced-port laparoscopic surgery with complete D2 lymph node (LN) dissection for gastric cancer is a safe and feasible surgical technique. The prospectively enrolled 65 gastric cancer patients underwent reduced-port surgery (i.e., triple-incision totally laparoscopic distal gastrectomy [Duet TLDG] with D2 lymphadenectomy). Compliance rate was the primary outcome, which was defined as cases in which there was no more than one missing LN station during D2 LN dissection. The secondary outcomes were the numbers of dissected and retrieved LNs in each station and other short-term surgical outcomes and postoperative course. The compliance rate was 58.5%. The total number of retrieved LNs was 41 (range: 14–83 LNs). The most common station missing from LN retrieval was station no. 5 (35/65; 53.8%), followed by station no. 1 (24/65; 36.9%). The overall postoperative complication rate was 20.0% (13/65). One patient underwent surgical treatment for postoperative complications. There was no instances of mortality. Duet TLDG is an oncologically and technically safe surgical method of gastrectomy and D2 lymphadenectomy.

Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be performed in both primary and distant metastatic sites.

Surgical results including postoperative complications, prognoses, body weight changes, and nutritional statuses were compared in patients with early gastric cancer in the upper third of the stomach who were treated by total gastrectomy or proximal gastrectomy. The authors reviewed clinicopathologic features, postoperative complications, survivals, body weight changes, and biochemical markers after surgery in 423 patients who underwent total or proximal gastrectomy for early gastric cancer in the upper third of the stomach. The proximal gastrectomy group (n = 89) had smaller tumors, shorter resection margins, and smaller numbers of retrieved lymph nodes than the total gastrectomy group (n = 334). N stages and 5-year survival rates were similar after total and proximal gastrectomy. Postoperative complication rates after total gastrectomy and proximal gastrectomy were 12.6% and 61.8%, respectively, which was significant ( P < .001). Rates of anastomotic stenosis and reflux esophagitis were 6.9% and 1.8% after total gastrectomy and 38.2% and 29.2% after proximal gastrectomy, respectively. The parameters that reflect nutritional status (ie, body weight, serum hemoglobin, total protein, albumin, glucose, and cholesterol) were similar in the proximal and total gastrectomy groups at 6, 12, 24, and 36 months postoperatively. Although the surgical safeties and curabilities of proximal and total gastrectomy were similar, proximal gastrectomy was found to be associated with a markedly higher rate of complications such as anastomotic stenosis and reflux esophagitis and to provide no benefit in terms of postoperative weight loss. The authors conclude that proximal gastrectomy is not a better option for upper-third early gastric cancer than total gastrectomy.

Gastric cancer (GC) patients usually receive surgical treatment. Postoperative therapeutic options such as anticancer adjuvant therapies (AT) based on prognostic prediction models would provide patient-specific treatment to decrease postsurgical morbidity and mortality rates. Relevant prognostic factors in resected GC patient’s serum may improve therapeutic measures in a non-invasive manner. In order to develop a GC prognostic model, we designed a retrospective study. In this study, serum samples were collected from 227 patients at a 4-week recovery period after D2 lymph node dissection, and 103 cancer-related serum proteins were analyzed by multiple reaction monitoring mass spectrometry. Using the quantitative values of the serum proteins, we developed SEPROGADIC (SErum PROtein-based GAstric cancer preDICtor) prognostic model consisting of 6 to 14 serum proteins depending on detailed purposes of the model, prognosis prediction and proper AT selection. SEPROGADIC could clearly classify patients with good or bad prognosis at each TNM stage (1b, 2, 3 and 4) and identify a patient subgroup who would benefit from CCRT (combined chemoradiation therapy) rather than CTX (chemotherapy), or vice versa. Our study demonstrated that serum proteins could serve as prognostic factors along with clinical stage information in patients with resected gastric cancer, thus allowing patient-tailored postsurgical treatment.

With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers—HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren’s classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.

Purpose Although the suicide rate of cancer survivors is higher than that of the general population, few studies have examined the potential risk factors. We assessed suicide ideation (SI) and investigated its correlates among survivors of stomach cancer, which is one of the most prevalent cancers in Korea. Methods We surveyed 378 stage I–III stomach cancer survivors who had been disease free for at least 1 year. The survey contained demographic questions and quality of life assessments from the European Organization for Research and Treatment of Cancer QLQ-C30 and its stomach cancer-specific module, the McGill Quality of Life Questionnaire, the Brief Fatigue Inventory, and one question from the Beck Depression Inventory. Results We found that 131/378 stomach cancer survivors (34.7 %) experienced SI. Univariate analyses showed that SI was significantly associated with income, comorbidity, smoking, and the following quality of life factors: general health status, emotional functioning, fatigue, nausea/vomiting, dyspnea, appetite loss, constipation, diarrhea, financial problems, eating restriction, anxiety, dry mouth, trouble belching, hair loss, body image, existential well-being, and social support. Multivariate logistic regression confirmed that SI was independently associated with diarrhea (adjusted odds ratio (aOR) 2.84; 95 % confidence interval (CI) 1.44–5.62), hair loss (aOR 2.77; 95 % CI 1.04–7.36), existential well-being (aOR 6.18; 95 % CI 2.91–13.1), and usual fatigue (aOR 2.29; 95 % CI 1.30–4.06). Conclusion Our findings reveal a high prevalence of SI among stomach cancer survivors and identify health-related quality of life issues such as diarrhea, hair loss, existential well-being, and fatigue as important risk factors of SI.

BackgroundLimited 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.MethodsBetween 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.ResultsThe 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.ConclusionsBecause 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.

Few studies have compared the long-term outcomes of endoscopic resection and surgery. The aim of this study was to compare the long-term outcomes of endoscopic resection with those of surgery for early gastric cancer (EGC). We reviewed prospectively collected data of patients who had undergone endoscopic resection (1,290 patients) or surgery (1,273 patients) for EGC. To reduce the effect of selection bias, we performed a propensity score-matching analysis between the two groups. The primary outcome was overall survival (OS). The secondary outcomes were disease-specific survival, disease-free survival (DFS), recurrence-free survival (RFS), occurrence of metachronous gastric cancer, treatment-related complications, length of hospital stay, and 30-day outcomes. The study was designed as a non-inferiority study and tested in an intention-to-treat analysis. In a propensity-matched analysis of 611 pairs, the 10-year OS proportion was 96.7% in the endoscopic resection group and 94.9% in the surgery group (P=0.120) (risk difference -1.8%, 95% confidence interval (CI) -4.04-0.44, Pnon-inferiority=0.014), which met the non-inferiority criterion. In contrast, the 10-year RFS proportion was 93.5% in the endoscopic resection group and 98.2% in the surgery group (P<0.001) (risk difference 4.7%, 95% CI 2.50-6.97, Pnon-inferiority=0.820), which did not meet the non-inferiority criterion, mainly because of metachronous recurrence in the endoscopic resection group. The rate of early complications was higher in the endoscopic resection group than in the surgery group (9.0 vs. 6.6%, P=0.024), whereas the rate of late complications was higher in the surgery group than in the endoscopic resection group (0.5 vs. 2.9%, P<0.001). In the multiple Cox regression analysis, patient's age, the comorbidity index, the performance index, sex, tumor morphology, and depth of invasion were predictors of OS in patients with EGC. Endoscopic resection might not be inferior to surgery with respect to OS in patients with EGC lesions that meet the absolute or expanded criteria. However, DFS, RFS, and metachronous RFS might be lower after endoscopic resection than after surgery.