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We investigated the clinicopathological features and management for superficial nonampullary duodenal tumors (SNADTs). The safety and feasibility of laparoscopic management, especially laparoscopic endoscopic cooperative surgery (LECS), were evaluated.A total of 59 patients with SNADTs who underwent operations from January 2009 to December 2018 at all 8 institutions of the Catholic Medical Center were identified in our comprehensive multi-institutional database. Clinicopathological and surgical data on the 4 anatomical regions of the duodenum were collected and compared. Characteristics of conventional laparoscopic procedure (laparoscopy-only) and LECS procedures were also compared.There were significantly more asymptomatic patients with tumors in the first and secondMost of the SNADTs located in proximal duodenum were detected incidentally. GISTs were the most common diagnoses of SNADTs in all locations. In treating these tumors, laparoscopic resection is safe and feasible. Especially, LECS may be ideal for treating small endophytic tumors, minimizing over-resection and postoperative complications.

Tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) are standard adjuvant chemotherapies (ACs) administered after gastrectomy to patients with stage II or III gastric cancer. However, the efficacy of AC in elderly patients remains unclear. The objective of this retrospective multicenter cohort study was to compare the efficacies of S-1 and CAPOX AC in patients aged ≥70 years.Nine hundred eighty-three patients who were treated with AC using S-1 (768 patients) or CAPOX (215 patients) were enrolled in this study. Each patient underwent AC after curative gastrectomy for stage II or III gastric cancer at one of 27 hospitals in the Republic of Korea between January 2012 and December 2013. Relapse-free survival (RFS) and overall survival (OS) were analyzed according to AC regimen and age group.Of the 983 patients, 254 (25.8%) were elderly. This group had a similar RFS (P=0.099) but significantly poorer OS (p=0.003) compared with the non-elderly group. Subgroup analysis of the non-elderly group revealed no AC-associated differences in survival. Subgroup analysis of the elderly group revealed significantly better survival in the S-1 group than in the CAPOX group (RFS, P0.001; OS, P0.001). Multivariate analysis revealed that the CAPOX regimen was an independent poor prognostic factor for RFS (hazard ratio [HR], 1.891; 95% confidence interval [CI], 1.072-3.333; P=0.028) and OS (HR, 2.970; 95% CI, 1.550-5.692; P=0.001).This multicenter observational cohort study found significant differences in RFS and OS between S-1 and CAPOX AC among patients with gastric cancer aged ≥70 years.

This study presents the initial feasibility of three-port right-side approach-duet totally laparoscopic distal gastrectomy (R-duet TLDG) with uncut Roux-en-Y (R-Y) reconstruction for the treatment of lower- or middle-third gastric cancer.A total of 30 patients who underwent R-duet TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at the Catholic Medical Center. Reconstructions were performed intracorporeally without special instruments. The clinicopathological characteristics, operative details, postoperative short-term outcomes, and postoperative follow-up endoscopy results were analyzed retrospectively.All operations were performed by three-port R-duet TLDG. There were no conversions to an open approach, and no additional ports were placed. The mean operating time was 170 minutes, and the mean number of retrieved lymph nodes was 44. Three patients experienced mild postoperative complications, including small bowel ileus and pneumonia. Follow-up endoscopy was carried out at 3 months. No patients had experienced moderate-or-severe food stasis, alkaline gastritis, or bile reflux during the follow-up period. Recanalization of the biliopancreatic limb was not observed.R-duet TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery without special instruments.

Neuropilin-1 (NRP-1) is known to be related to various types of cancer and is considered a novel tumor marker or therapeutic target. The aim of this study was to identify the clinical implications of NRP-1 expression in terms of prognosis in patients with gastric cancer. A total of 265 patients who underwent radical gastrectomy for the treatment of gastric cancer from 2008 to 2011 were included in this retrospective study. NRP-1 expression of tumors was determined by immunohistochemistry. The patients’ clinicopathological characteristics, operative details, and long-term outcomes were retrospectively analyzed. A total of 181 (68.3%) patients demonstrated expression of NRP-1. No survival difference was observed according to NRP-1 expression in any patient. The patients were divided into the gland formation (GF) and the no gland formation (nGF) types, according to histology. NRP-1 expression rates were 65.6% (84/128) and 70.8% (97/137), respectively. NRP-1 expression was not an independent prognostic factor in the GF group, although patients who expressed NRP-1 had better survival outcomes. In contrast, patients who expressed NRP-1 in the nGF group had worse 5-year survival rates (p = 0.027), and NRP-1 was an independent prognostic factor in a multivariate analysis (hazard ratio, 1.923; 95% confidence interval, 1.041–3.551). NRP-1 expression in patients with nGF type gastric cancer is predictive of a poor prognosis.

Background We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. Methods Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0–0.1, 0.1–0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. Results After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. Conclusions LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1. Trial registration Not applicable (retrospective study).

The acquisition of an invasive phenotype by a tumor cell is a crucial step of malignant transformation. The underlying genetic mechanisms in gastric cancer (GC) are not well understood. We performed whole-exome sequencing of 15 pairs of primary GC and their matched lymph node (LN) metastases (10 primary GCs with single matched LNs and 5 primary GCs with three LNs per case, respectively). Somatic alterations including single nucleotide variations, short insertions/deletions including locus-level microsatellite instability and copy number alterations were identified and compared between the primary and metastatic LN genomes. Mutation abundance was comparable between the primary GC and LN metastases, but the extent of mutation overlap or the mutation heterogeneity between primary and LN genomes varied substantially. Primary- or LN-specific mutations could be distinguished from common mutations in terms of mutation spectra and functional categories, suggesting that the mutation forces are not constant during gastric carcinogenesis. A spatial distribution revealed TP53 mutations as common mutations along with a number of region-specific mutations, such as primary-specific SMARCA4 and LN-specific CTNNB1 mutations. The subclonal architectures of common mutations were largely conserved between primary GC and LN metastatic genomes. The mutation-based phylogenetic analyses further showed that LN metastases may have arisen from homogeneous subclones of primary tumors. The abundance and spatial distribution of mutations may provide clues on the evolutionary relationship between primary and matched LN genomes. Gene-level analyses further distinguished the early addicted cancer drivers such as TP53 mutations from late acquired region-specific mutations.

This study aimed to investigate the clinicopathologic characteristics and outcomes of Borrmann type 1 gastric cancer and evaluate its clinical significance in advanced gastric cancer compared with Borrmann types 2 and 3 cancer. Between January 1989 and December 2013, 1949 patients with advanced gastric cancer who underwent curative gastrectomy at our institution were enrolled in the study. Of the 1949 patients, 59 (3%) exhibited Borrmann type 1 cancer, characterized by a large size, rare serosal invasion, lower lymph node involvement, location in the upper third of the stomach, intestinal type, and differentiated histology. The recurrence rate was higher for Borrmann type 1 than for Borrmann types 2 and 3 cancer. In addition, more than half of the Borrmann type 1 recurrences showed a hematogenous pattern. However, overall survival did not differ significantly among the three cancer types. In the multivariate analysis, Borrmann type 1 cancer, with tumor depth, node metastasis, and vascular invasion, was an independent risk factor associated with recurrence. Particularly, Borrmann type 1 cancer showed a worse prognosis in both overall survival and recurrence-free survival than the other Borrmann types in the upper third of the stomach. Borrmann type 1 gastric cancer is associated with a higher recurrence rate than Borrmann types 2 and 3, but not with a difference in the overall survival rate.

After curative resection of gastric cancer with D2 lymph node dissection, postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin (XELOX) is considered to be standard therapy in Eastern countries. This study aimed to compare the efficacies of adjuvant S-1 and XELOX chemotherapy for gastric cancer patients after D2 dissection based on disease-free survival (DFS). This retrospective observational study was conducted at 29 tertiary hospitals in Korea. Of 1898 patients who underwent curative resection and received adjuvant chemotherapy for gastric cancer between February 2012 and December 2013, 1088 patients who met the eligibility criteria were enrolled in the study. After propensity score-matching, the 3-year disease-free survival rate (DFS) was used to compare efficacies directly between adjuvant XELOX and S-1 chemotherapies for patients with stage 2 or 3 gastric cancer after D2 gastrectomy. The 3-year DFS rates for the S-1 and XELOX groups did not differ significantly among disease stages 2A, 2B, and 3A (all p > 0.05). However, the survival rates for the S-1 group were significantly lower than for the XELOX group for stage 3B (65.8% vs. 68.6%; p = 0.019) and stage 3C (48.4% vs. 66.7%; p = 0.002) gastric cancer. The hazard ratios (HRs) of S-1 chemotherapy for recurrence compared with XELOX for stages 3B and 3C were respectively 2.030 [95% confidence interval (CI), 1.110–3.715; p = 0.022] and 2.732 (95% CI 1.427–5.234; p = 0.002). Adjuvant XELOX chemotherapy was more effective than S-1 for patients with stage 3B or 3C gastric cancer after D2 lymph node dissection.

Surgical archives of tumor specimens are often impure. The presence of RNA transcripts from nontumor cells, such as immune and stromal cells, can impede analyses of cancer expression profiles. To systematically analyze the impact of tumor purity, the gene expression profiles and tumor purities were obtained for 7,794 tumor specimens across 21 tumor types (available in The Cancer Genome Atlas consortium). First, we observed that genes with roles in immunity and oxidative phosphorylation were significantly inversely correlated and correlated with the tumor purity, respectively. The expression of genes implicated in immunotherapy and specific immune cell genes, along with the abundance of immune cell infiltrates, was substantially inversely correlated with tumor purity. This relationship may explain the correlation between immune gene expression and mutation burden, highlighting the need to account for tumor purity in the evaluation of expression markers obtained from bulk tumor transcriptome data. Second, examination of cluster membership of gene pairs, with or without controlling for tumor purity, revealed that tumor purity may have a substantial impact on gene clustering across tumor types. Third, feature genes for molecular taxonomy were analyzed for correlation with tumor purity, and for some tumor types, feature genes representing the mesenchymal and classical subtypes were inversely correlated and correlated with tumor purity, respectively. Our findings indicate that tumor purity is an important confounder in evaluating the correlation between gene expression and clinicopathologic features such as mutation burden, as well as gene clustering and molecular taxonomy. Cancer Immunol Res; 6(1); 87–97. ©2017 AACR.

The prognosis of gastric cancer is generally determined by tumor depth and lymph node metastasis, while the effect of cross-sectional tumor location on prognosis remains unclear. This study recruited patients who had been diagnosed with gastric cancer and who underwent gastrectomy from 1989 to 2012. The cross-sectional locations of the gastric cancers were classified into four regions: the lesser (LC) and greater curvatures (GC), and anterior (AW) and posterior walls (PW). Overall, 4820 patients were enrolled in this study. The most common site of gastric cancer among the four cross-sectional locations was the LC (46.4%), while the proportions of PW (19.9%), AW (18.4%), and GC (15.4%) were similar. Overall survival differed statistically (p = 0.013) according to the cross-sectional location, and the 5-year overall survival of those with tumors with a GC location was significantly worse (p = 0.003) than for the other three locations. In subgroup multivariate analysis, GC location was an independent prognostic indicator for a worse clinical outcome at T stage 3–4b (hazard ratio 1.365, 95% confidence interval 1.150–1.620, p

Background The curative surgical treatment of gastric cancer in the current laparoscopic surgical era relies on the surgeon's preference, technical difficulties, and concerns regarding outcome have led to the availability of totally laparoscopic distal gastrectomy (TLDG) and laparoscopic-assisted distal gastrectomy (LADG). A consensus on which of the two procedures is preferable is necessary. Therefore, the aim of this study was to evaluate the differences between LADG and TLDG in terms of surgical outcomes, postoperative recovery, pain, and complications. Methods PubMed, Google Scholar, Medline, Embase, and Cochrane databases were explored up to 2017 to evaluate TLDG and LADG. Parameters including surgical outcomes, postoperative recovery, and postoperative complications were subjected to meta-analysis to calculate the odds ratio and weighted mean difference with 95% confidence intervals (c.i.). Results Twenty-five studies (24 non-RCT and 1 RCT) with a total of 4562 gastric cancer patients were included in the meta-analysis. Under reconstruction-matched analysis, overall complications and anastomotic complications were similar for TLDG and LADG. Nevertheless, short-term outcomes such as blood loss, time to first soft diet, hospital stay, analgesic use, and CRP level were favourable for TLDG, while all other surgical outcomes showed no difference. Conclusions TLDG and LADG did not show significant differences in surgical outcomes and postoperative complications, including anastomotic-related morbidity. Therefore, decisive factors in selecting surgical procedures, which previously consisted of surgical outcomes, have been superseded by extra-surgical values such as cosmesis, economics, and patient's quality of life. These factors will be explored in a future multicentre prospective study (KLASS07 trial).

Background The CD133 transmembrane protein is a well-recognized stem cell marker that has been used to isolate putative cancer stem cell populations from gastric cancers (GCs). However, the molecular features or biomarkers underlying CD133 are largely unknown in GCs. Methods We performed gene expression profiling of CD133+ and CD133- cells sorted by flow cytometry from three GC cell lines to identify the CD133 expression signatures of GC. The CD133 expression signatures were investigated across publicly available expression profiles of multiple tumor types including GC and also for their relationship with patient survival. Results The CD133 signature genes defined as 177 upregulated genes and 129 downregulated genes in CD133+ cells compared to CD133- cells were enriched with genes involving the cell cycle and cytoskeleton, implying that cancer stem cells with unlimited self-renewal play cancer-initiating roles. The CD133 expression signatures in GC expression profiles were positively correlated with those of brain tumors expressing CD133 and human embryonic stem cells, emphasizing the transcriptional similarities across stem cell-related expression signatures. We also found that these stem cell expression signatures were inversely correlated with those representing tumor infiltrating immune and stromal cells. Additionally, high CD133 expression signatures were found in intestinal subtypes and low tumor stage GCs as well as in those with microsatellite instabilities and high mutation burdens. As examined across 20 additional tumor types, both the expression signatures representing CD133 and stromal cells were unfavorable prognostic features; however, their impact were variable across tumor types. Conclusions The transcriptional activities of CD133 and those of stromal cells representing the activity of stem cells and level of epithelial-to-mesenchymal transition, respectively, may be inversely correlated with each other across multiple tumor types including GC. This relationship may be a confounding factor and should therefore be considered when evaluating the clinical relevance of stem cell-related markers. Electronic supplementary material The online version of this article (10.1186/s12885-019-5332-y) contains supplementary material, which is available to authorized users.

Background Gastric cancer (GC) follow-up schedule after curative surgery is universally recommended based on the pathologic stage, but their details, including intervals and modalities of surveillance have not yet been standardised. The aim of this study was to investigate the characteristics of GC recurrence by stage to establish optimal postoperative surveillance strategies. Methods Medical information on 5095 patients with GC who underwent curative intent gastrectomy in our institution between January 1989 and December 2013 was reviewed retrospectively. Moreover, 656 patients who had recurrences after radical surgery were identified. Clinicopathologic characteristics, timing and pattern of recurrence, and survival data of these patients were analysed. Results Among the 656 patients, 50 (7.6%), 123 (18.8%), and 483 (73.6%) had stages I, II, and III GC, respectively. The median times to initial recurrence in patients with stages I, II, and III GC were 23.5 months (interquartile range [IQR], 13.0–33.0 months), 13.0 months (IQR, 9.0–25.0 months), and 12.0 months (IQR, 7.0–21.0 months), respectively. In patients with stage I GC, more than half (58%) of them had distant organ metastasis; otherwise, peritoneal dissemination (39%) was the most common pattern in patients with stage III GC. Conclusions Despite the low incidence, the time of initial recurrence in stage I GC was longer than those in stage II and III GC. Moreover, the pattern of initial recurrence was also different according to the pathologic stage. Therefore, clinicians should consider stage-specific differences of recurrence in setting up surveillance strategies after curative surgery for GC patients.

The prevalence of gastroesophageal reflux disease (GERD) is increasing in Korea, and physicians, including surgeons, have been focusing on its treatment. Indeed, in Korea, medical treatment using a proton pump inhibitor is the mainstream treatment for GERD, while awareness of surgical treatment is limited. Accordingly, to promote the understanding of surgical treatment for GERD, the Korean Anti-Reflux Surgery Study Group published the Evidence-Based Practice Guideline for the Surgical Treatment of GERD. The guideline consists of 2 sections: fundamental information such as the definition, symptoms, and diagnostic tools of GERD and a recommendation statement about its surgical treatment. The recommendations presented 5 debates regarding fundoplication: 1) comparison of the effectiveness of medical and surgical treatments, 2) effectiveness of surgical treatment in cases of refractory GERD, 3) effectiveness of surgical treatment of extraesophageal symptoms, 4) comparison of effectiveness between total and partial fundoplication, and 5) effectiveness of fundoplication in cases of hiatal hernia. The present guideline is the first to demonstrate the efficacy of the surgical treatment GERD in Korea.

Purpose To date, no studies have been performed on staging based on the lymph node ratio (LNR) in elderly patients with gastric cancer who may require limited lymph node (LN) dissection due to morbidity and tissue fragility. We aimed to develop a new N staging system using the LNR in elderly patients with gastric cancer. Materials and methods The present study included patients aged over 75 years who underwent curative gastrectomy between January 1989 and December 2018. Clinicopathological data including the number of retrieved and metastatic LNs were collected and the LNR values were obtained (LNR = the number of metastatic LNs/the number of retrieved LNs). Eleven LNR groups with intervals of 0.1 were divided into four stages based on the inflection points at which the hazard ratio (HR) increased. Survival analysis was performed to evaluate the prognostic value of the LNR. Results The four LNR stages included LNR0 (n=364), LNR1 (n=128), LNR2 (n=103), and LNR3 (n=10). In the multivariate analysis, both N staging and LNR staging exhibited significant prognostic values for predicting survival outcomes. However, the incremental change in the hazard ratio (HR) between consecutive stages was greater for the LNR staging than for the N staging (HRs: 1.607, 2.758, and 3.675 for N staging; 1.583, 3.514, and 10.261 for LNR staging). Conclusions LNR staging is more useful than N staging in predicting the prognosis in elderly patients with gastric cancer and may be used as a complement or alternative to N staging.

Background: Urgent surgery performed for appendicitis is hypothesized to avoid complications such as perforation or abscess. This study aimed to evaluate the effect of the timing of surgery on the complications of laparoscopic appendectomy. Methods: A retrospective review of 4,065 patients who underwent a laparoscopic appendectomy was conducted. The demographic data, time of presentation, physical findings, diagnostic data and complications were recorded. The patients were divided into 4 groups (Group A, 0-6 h; Group B, 6-12 h; Group C, 12-18 h; Group D, over 18 h) based on the time elapsed from the evaluation at the emergency room to the appendectomy. Results: Group A consisted of 2,084 (51.3%) patients, Group B consisted of 1,553 (38.2%) patients, Group C consisted of 388 (9.5%) patients and Group D consisted of 40 (1.8%) patients. A perforated appendicitis was observed in 560 (13.8%) patients. Postoperative complications developed in 293 (7.2%) patients. No significant differences in perforation and postoperative complications were observed between the 4 groups. Conclusion: The timing of surgery did not affect the incidence of complications or perforated appendicitis.

442 Background: Neuropilin-1 (NRP-1) is known to be related with various types of cancer and considered as a novel tumor marker or a therapeutic target. The aim of the study is to identify the clinical implication of NRP-1 expression in terms of prognosis in gastric cancer. Methods: A total of 265 patients who underwent radical gastrectomy for the treatment of gastric cancer from 2008 to 2011 were included. NRP-1 expression of tumors was determined by immunohistochemistry. Patients’ clinicopathologic characteristics, operation details, and long-term outcomes were retrospectively analyzed. Results: 181 (68.3%) patients showed NRP-1 expression. There was no survival difference according to the NRP-1 expression in all patients. The patients were divided into gland formation (GF) type and no gland formation (nGF) type according to histologic type. NRP-1 expression rates were 65.6% (84/128) and 70.8% (97/137), respectively. In the group of GF, NRP-1 expression was not independent prognostic factor, although patients with NRP-1 expression had better survival outcome. In contrast, patients with NRP-1 expression had worse 5-year survival rate in the group of nGF (p = 0.027) and it was an independent prognostic factor multivariate analysis (HR, 1.923; 95% CI, 1.041 - 3.551). Conclusions: NRP-1 expression in the nGF type gastric cancer predicts a poor prognosis.

294 Background: The role of controlling nutritional status (CONUT) score in predicting cancer survival remains uncertain. This study aimed to investigate the predictive value of the CONUT score and to develop a more appropriate scoring system beyond CONUT for gastric cancer (GC). Methods: We retrospectively reviewed 1307 patients who underwent curative gastrectomy between 2009 and 2015. The CONUT and three modified scores with modified lipid components (L-CONUT: albumin/total lymphocyte count [TLC]/low density lipoprotein, H-CONUT: albumin/TLC/high density lipoprotein, and T-CONUT: albumin/TLC/triglyceride) were calculated. The predictive value of each scoring system on long-term survival was assessed. Results: The values of the four nutritional scores were categorized into three groups (low, medium, and high). The CONUT (P < 0.001), L-CONUT (P < 0.001), H-CONUT (P < 0.001), and T-CONUT (P < 0.001) scores showed significant differences in overall survival in the three groups. Survival analysis according to the pathological stage showed that advanced age, Eastern Cooperative Oncology Group performance status, male sex, and high H-CONUT score (HR, 3.93; 95% CI, 1.81–8.55; P = 0.001) were independent worse prognostic factors for overall survival in the stage I group. In the stage II group, CONUT score (HR, 5.077; 95% CI, 1.65–15.65; P = 0.005) was significantly associated with poor prognosis. In the stage III group, no scoring system showed significant results. Conclusions: In advanced GC (beyond stage II), the prognostic impact of the nutritional scoring system was uncertain. However, the H-CONUT score is a promising indicator of prognosis in stage I GC, and the CONUT score is useful for predicting long-term survival in stage II GC.

According to 8th AJCC/UICC TNM criteria, stage IIB includes pT1N3M0, pT2N2M0, pT3N1M0, and pT4aN0M0, which includes not only early gastric cancer but also locally advanced cancer. There are currently no data about whether there is any additional impact of serosal exposed cancer without nodal metastasis (pT4aN0) on patients’ survival outcomes compared with other subgroups in IIB. Patients who underwent radical gastrectomy for gastric cancer patients were enrolled, including 427 patients in stage IIB; 20 (4.68%), 104 (24.35%), 172 (40.28%), and 131 (30.67%) patients were classified as pT1N3a, pT2N2, pT3N1, and pT4aN0, respectively. Clinicopathological characteristics, recurrence pattern, and survival and recurrence rates were analyzed according to the TNM subgroups. Cancer-specific and relapse-free survival were significantly worse in serosal exposed cancer than in nonserosal exposed cancer in stage IIB (P = 0.019 and P = 0.015). Recurrence rate was highest in the pT4aN0 subgroup (29.0%) in stage IIB, and peritoneal metastasis was the most common pattern. Survival outcomes of the pT4aN0 subgroup were not significantly different from those of the stage IIIA or pT4aN1 subgroups. Patients with serosal exposed cancer without nodal metastasis shows worse cancer specific and disease-free survival with higher incidence of peritoneal metastasis than other subgroups in stage IIB. Further surveillance studies, including staging laparoscopy and active adjuvant therapy, are required in this subgroup of patients.

Purpose The surgical outcomes of end-stage renal disease (ESRD) patients undergoing radical gastrectomy for gastric cancer were inferior compared with those of non-ESRD patients. This study aimed to evaluate the short- and long-term surgical outcomes of ESRD patients undergoing laparoscopic gastrectomy (LG) and open gastrectomy (OG) for gastric cancer. Materials and methods Between 2004 and 2014, 38 patients (OG: 21 patients, LG: 17 patients) with ESRD underwent gastrectomy for gastric cancer. Comparisons were made based on the clinicopathological characteristics, surgical outcomes, and long-term survival rates. Results No significant differences were noted in the clinicopathological characteristics of either group. LG patients had lower estimated blood loss volumes than OG patients (LG vs. OG: 94 vs. 275 mL, P=0.005). The operation time and postoperative hospital stay were similar in both the groups. The postoperative morbidity for LG and OG patients was 41.1% and 33.3%, respectively (P=0.873). No significant difference was observed in the long-term overall survival rates between the 2 groups (5-year overall survival, LG vs. OG: 82.4% vs. 64.7%, P=0.947). Conclusions In ESRD patients, LG yielded non-inferior short- and long-term surgical outcomes compared to OG. Laparoscopic procedures might be safely adopted for ESRD patients who can benefit from the advantages of minimally invasive surgery.

BACKGROUND: Despite the development of newer treatments, the prognosis for patients with stage IV gastric cancer remains grave. This study evaluated the efficacy of gastrectomy following response to chemotherapy in patients with stage IV gastric cancer.A total of 419 patients who were diagnosed with stage IV gastric cancer were identified from the multi-institutional Catholic Gastric Cancer Study Group database. The patients were divided into four groups: 212 were in the chemotherapy only (CTx) group, 124 were in the chemotherapy after palliative gastrectomy (G-CTx) group, 23 were in the radical gastrectomy after chemotherapy (CTx-G) group, and 60 were in the best supportive care group. To compensate for the effects of chemotherapy, cases of chemotherapy responsive were analyzed separately. To identify factors affecting survival rates, cure rates for surgery in the surgery group were analyzed.The 3-year survival rate of the CTx-G group was significantly higher than that of the CTx group (42.8 vs. 12.0%, p = 0.001). Moreover, the CTx-G group's 3-year survival rate was greater than that of the G-CTx group (42.8 vs. 37.1%, p = 0.207). Chemotherapy-responsive patients in the CTx-G group had a better 3-year survival rate than those in the G-CTx group (46.1 vs. 18.4%, respectively, p = 0.011). In the surgery group, R0 resection led to a significantly better 3-year survival rate than palliative gastrectomy (61.1 vs. 16.2%, p = 0.003).Adjuvant surgery might improve the survival rate of patients with stage IV gastric cancer, particularly in R0 resection cases.

Background Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. Methods In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. Results DKK1 expression was high in 73 (46.2%) patients, while ß-catenin expression was positive in 51 (32.3%) patients. The expression of DKK1 was positively correlated with that of ß-catenin (P

Our goal was to evaluate changes in PD-L1 expression in primary tumours of metastatic gastric cancer before and after chemotherapy. We evaluated the PD-L1 expression of 72 patients with primary gastric cancer, before and after palliative first-line platinum-based chemotherapy, between January 2015 and March 2017. The PD-L1 ratio was defined as pre-chemotherapy PD-L1 expression divided by the post-chemotherapy PD-L1 expression. In 30 patients with PD-L1 negative pre-chemotherapy, 12 (40%) were positive post-chemotherapy; among the 42 patients with PD-L1 positive pre-chemotherapy, 24 (57.1%) were negative post-chemotherapy. The degree of PD-L1 expression decreased from 58.3% before chemotherapy to 41.7% after chemotherapy (P = 0.046). Among patients with complete response/partial response (CR/PR), the degree of PD-L1 expression decreased (P = 0.002), as well as PD-L1 positivity with statistical significance (P = 0.013) after chemotherapy, but not among patients with stable disease/progressive disease (SD/PD). Higher disease control rates (CR/PR/SD) were observed in patients with an elevated PD-L1 ratio (P = 0.043). Patients with a high PD-L1 ratio (> 1) were found to be associated with a better progression-free survival (HR 0.34, 95% CI 0.17–0.67, P = 0.002). PD-L1 expression can change during chemotherapy. Moreover, changes in patterns of PD-L1 expression might be associated with patient prognosis and response to chemotherapy.

The aim of this study was to evaluate the incidence and clinical characteristics of splenic infarction (SI) in gastric cancer patients who have undergone gastrectomy. For this study, the medical records of 1084 patients were reviewed and 877 patients were ultimately enrolled. The times of symptom onset, diagnosis of SI, and complete resolution on CT were calculated from the day of the operation. Based on the wedge shape of the SI in all cases, the total volume of the SI was measured based on that of a corn kernel. Thirty-six patients (4.10%) were diagnosed with SI after gastrectomy; four of these patients (0.45%) developed complications associated with the SI. Total gastrectomy and extended lymph node dissection were risk factors for development of SI. Patients with complications exhibited inflammatory signs between 7 and 10 days after surgery. The mean volume of the SI was 4025.69 mm3. The mean time to complete resolution on the CT scan was 327 days postoperatively. In 30 cases, small branched arteries from the splenic artery that could have caused the SI were retrospectively detected on the preoperative CT scans. Although the incidence of the SI was low, large volume of the SI is associated with complication development. Measuring the infarction volume via a CT scan may be useful to decide on the treatment strategy. Preoperative 3-D reconstruction of the splenic artery tributaries may help reduce the risk of inadvertent SI.

Multidetector computed tomography (MDCT) is essential for the prediction of lymph node (LN) metastasis in gastric cancer. However, the measurement method and size criteria for metastatic LNs using MDCT are unclear.MDCTs of gastric cancer patients who underwent surgery and had pathological staging were reviewed by radiologists. The two-dimensional cutoff values for LNs with suspected metastasis were calculated, and clinicopathological data were analyzed using those cutoff values.The total number of enrolled patients was 327. The cutoff values of the maximal area with metastatic LNs were obtained significantly at stations 3, 4, and 6, and those values were 112.09, 33.79, and 85.88 mm(2), respectively. The common cutoff value was 112.09 mm(2), and the area under the curve was 0.617 (P = 0.002). The overall survival rate of the patients with LNs less than 112.09 mm(2) was significantly better than those with LNs greater than 112.09 mm(2) (P0.001). In multivariate analysis, the maximal LN area was an independent prognostic factor (adjusted hazard ratio, 1.697 [95% confidence interval 1.116-2.582]).Using two-dimensional values for LNs measured by MDCT is a practical method of predicting metastatic LNs in gastric cancer. The maximal LN area value would be useful in both the preoperative staging and prognosis prediction of gastric cancer.

Gastric cancer is commonly treated via minimally invasive surgery. The present study explored the feasibility of right-side approach-duet (R-duet) totally laparoscopic distal gastrectomy using a three-port compared with a four- or five-port. A total of 251 patients who underwent curative totally laparoscopic distal gastrectomy for gastric cancer (72 R-duet, 74 four-port, and 105 five-port) at the Catholic Medical Center were enrolled. All operations were performed using conventional laparoscopic instruments. The clinicopathological characteristics, operative details, and postoperative short-term outcomes were analyzed retrospectively. The clinicopathological characteristics did not differ significantly among the groups, except that the N stage was higher in the five-port group. The operating time was significantly longer in the four-port than the R-duet group (R-duet, four-port, and five-port 148.2 ± 30.7, 162.4 ± 30.6, and 159.9 ± 31.5 min, respectively; p = 0.024). The estimated blood loss did not differ significantly. Postoperatively, the times to flatus and to soft diet consumption and the hospital stay were significantly longer in the five-port group. The extent of postoperative complications did not differ among the groups. R-duet totally laparoscopic distal gastrectomy is a reliable form of reduced-port surgery when used to treat gastric cancer; no special instruments are required.

Purpose Laparoscopic total fundoplication is the standard surgery for gastroesophageal reflux disease. However, partial fundoplication may be a viable alternative. Here, we conducted a nationwide survey of partial fundoplication in Korea. Methods The Korean Anti-Reflux Surgery study group recorded 32 cases of partial fundoplication at eight hospitals between September 2009 and January 2016. The surgical outcomes and postoperative adverse symptoms in these cases were evaluated and compared with 86 cases of total fundoplication. Results Anterior partial fundoplication was performed in 20 cases (62.5%) and posterior in 12 (37.5%). In most cases, partial fundoplication was a secondary procedure after operations for other conditions. Half of patients who underwent partial fundoplication had typical symptoms at the time of initial diagnosis, and most of them showed excellent (68.8%), good (25.0%), or fair (6.3%) symptom resolution at discharge. Compared to total fundoplication, partial fundoplication showed no difference in the resolution rate of typical and atypical symptoms. However, adverse symptoms such as dysphagia, difficult belching, gas bloating and flatulence were less common after partial fundoplication. Conclusion Although antireflux surgery is not popular in Korea and total fundoplication is the primary surgical choice for gastroesophageal reflux disease, partial fundoplication may be useful in certain conditions because it has less postoperative adverse symptoms but similar efficacy to total fundoplication.

Objectives This study analyzed the effect of D2 lymph node (LN) dissection on complications and survival in older patients with gastric cancer. Materials and Methods A total of 103 octogenarian patients who underwent curative gastrectomy for gastric cancer were divided into two groups (D2 and D1) according to the extent of LN dissection and analyzed retrospectively for complications and survival. Results No differences were observed in short-term postoperative outcomes, including complication rates, between the two groups. In a survival analysis, D2 LN dissection did not improve overall survival (OS) in any patient, including advanced cases. A Cox regression analysis revealed that the independent risk factors for OS were history of coronary artery disease (hazard ratio [HR], 11.095), postoperative short-term complications (HR, 9.939), and TNM stage (HR, 6.299). The extent of LN dissection was not an independent risk factor for OS, and D2 or more LN dissection (odds ratio, 10.89) increased the risk independently. Conclusions D2 or more LN dissection did not improve survival, but rather increased the risk of complications. Thus, LN dissection should be performed sparingly in octogenarian patients with gastric cancer.

Objective. Caveolin-1 (Cav-1), as the main component of caveolae, has complex roles in tumourigenesis in human malignancies. We investigated Cav-1 in primary and metastatic tumor cells of gastric cancer (GC) and its association with clinical outcomes. Methods. We retrieved 145 cases of GC who had undergone curative gastrectomy. The expression levels of Cav-1 was evaluated by immunohistochemistry, and its association with clinicopathological parameters and patient survival was analyzed. Results. High expression of Cav-1 protein of the GC in the stomach and metastatic lymph node was 12.4% (18/145) and 16.5% (15/91). In the multivariate analysis, tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882–8.224; P=0.001) and cancer-specific survival outcome (CSS, HR, 2.681; 95% CI, 1.613–8.623; P=0.002). Among the GCs with metastatic lymph node, it remained as a strong indicator of poor prognosis for RFS (HR, 3.136; 95% CI, 1.444–6.810; P=0.004) and CSS (HR, 2.509; 95% CI, 1.078–5.837; P=0.032). Conclusion. High expression of tumoral Cav-1 protein in metastatic lymph node is associated with unfavorable prognosis of curative resected GC, indicating the potential of novel prognostic markers.

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

BACKGROUND: Mechanisms of acquired resistance for EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) has been studied broadly, and T790M mutation, bypass singaling, and phenotype change have been suggested. Questions remain in terms of the selection of sub-clones according to the sites during EGFR TKI therapy, especially in brain due to blood-brain barrier. Three metastatic NSCLC patients harboring sensitive EGFR mutation were treated with EGFT TKI with good response but became refractory and symptomatic brain oligo-metastasis occurred. Metastectomy was done and next-generation sequencing (NGS) was done with the brain tissue and blood. MATERIAL AND METHODS: Fresh brain metastasis tissue was obtained during surgery and frozen in liquid nitrogen. Blood sampling was done within a week of the surgery and plasma was used for NGS. Amplicon sequencing (Thunderbolt) was performed. Library preparation and quality control sequencing amplicon libraries were prepared using ThunderBolts Cancer Panel, according to the manufacturer’s instructions. The ThunderBolts Cancer Panel uses 230 amplicons to interrogate mutations/hotspots in 50 oncogenes, tumor suppressors and drug resistance markers. RESULTS: All the 3 brain tissue had the same sensitive EGFR mutation (exon 19 deletion) as initial presentation, with PDGFRA, APC and TP53 mutations, while in the plasma, PDGFRA and APC mutations were identified in the 3 patients. From the case 1, PDGFRA, APC, MLH1 and EGFR mutations were identified in the plasma, and additional PIK3CA, KDR, TP53, ERBB2, and GNA11 mutations were found in the brain. From case 2, PDGFRA, APC, EGFR, MET, PTEN, HRAS, TP53 mutations were found in the plasma, and in the brain, PIK3CA, KDR, and ERBB2 mutations were identified in addition. From the case 3, PDGFRA, APC, HRAS, and TP53 mutations in the plasma, and additional EGFR mutation in the brain. CONCLUSION: Our data identified several additional mutations in brain metastasis compared to the plasma from patients with acquired EGFR TKI resistance, other than T790M mutation. Every mutation in the blood sample was identified in the brain tissue, while additional mutations were found in the brain tissue.

Background Guardix-SG is a poloxamer-based antiadhesive agent. The aim of this study was to investigate its efficacy in preventing abdominal adhesions in gastric cancer patients undergoing gastrectomy. Few clinical studies have reported that antiadhesive agent reduces the incidence of adhesion after gastrectomy. Methods We conducted a multicenter trial from June 2013 and August 2015 in patients with gastric adenocarcinoma undergoing radical gastrectomy. Patients were randomly assigned to the Guardix treatment or control group. Postoperative adhesions were diagnosed based on postoperative symptoms, plain x-ray films, and computed tomography. The primary endpoint of the study was the incidence of small bowel obstruction in the first postoperative year. The secondary end-point was the safety of Guardix-SG. Results The study included 109 patients in the Guardix group and 105 patients in the control group. The groups were similarly matched with pathological stage, operation type, anastomosis method, midline incision length, and the extent of lymph node dissection. Eight in the Guardix group and 21 in the control group experienced intestinal obstruction during the 1-year follow-up period. The cumulative incidence of small bowel obstruction was significantly lower in the Guardix group compared to that seen in the control group (4.7% vs 8.6% at 6 months and 7.3% vs 20% at 1 year; P = .007, log-rank test). There were no differences in postoperative complications and adverse events. Conclusion Guardix-SG significantly decreased the incidence of intestinal obstruction without affecting the incidence of postoperative complications.

TPS184 Background: Proximal gastrectomy (PG) is rarely performed for upper third early gastric cancer (EGC) because of postoperative reflux esophagitis. Recently, PG with double tract reconstruction was introduced and reported to have a reflux of approximately the same frequency as total gastrectomy (TG) with esophagojejunostomy. PG has several theoretical advantages over TG but has not yet been proven in randomized controlled trial. This study aimed to provide scientific evidence of laparoscopic PG with double tract reconstruction as a standard procedure for proximal EGC. Methods: The present trial is multicenter, prospective, randomized, controlled trial with superiority design. A total of 138 patients with upper third cT1N0M0 gastric adenocarcinoma are randomized to laparoscopic PG with double tract reconstruction and laparoscopic TG with esophagojejunostomy. Patients are enrolled for two years and followed up for two years. Primary co-endpoints are hemoglobin change and vitamin B12 cumulative supplement quantity after 2 years of operation. We used the alpha-split method to set the hemoglobin to 4% and vitamin B12 to 1% for alpha. The sample size needed was 62 patients for each arm. Accounting for 10% follow-up loss, the enrollment of 69 patients in each group was required. Secondary endpoints are prevalence rate of postoperative reflux esophagitis, morbidity and mortality, quality of life 2-year after operations, relapse-free survival, and overall survival. Nineteen investigators from 10 institutes participated in this trial. The first patient was enrolled on October 27, 2016 and we completed the patient enrollment on September 17, 2018. Clinical trial information: NCT02892643.

The extent of serosal exposure varies depending on the cross-section of the stomach that is viewed, affected by the visceral peritoneum of the omentum. Although multidetector computed tomography (MDCT) is the most useful method to predict serosal exposure, the MDCT criteria for such exposure by cross-sectional location remain to be established. The MDCT of gastric cancer patients who underwent surgery, and for whom pathological reports were available, were reviewed by radiologists. The MDCT criteria for invasion depth were divided into five grades: (1) smooth margin; (2) undulating margin; (3) streaky margin within vessels; (4) nodular margin within perigastric vessels; and (5) streaky or nodular margin over the perigastric vessels. The five grades were compared in terms of pathological tumor depth by curvature and wall group. A total of 125 patients of stage ≥ T2 were enrolled. The five MDCT grades correlated with tumor depth (P

Laparoscopic gastrectomy (LG) in gastric cancer patients with liver cirrhosis (LC) has rarely been reported. In this study, we aimed to elucidate the feasibility of LG compared with that of open gastrectomy (OG) for LC patients. Of the 75 LC patients who underwent radical gastrectomy for gastric cancer between April 2005 and March 2014, 36 patients who underwent LG were compared with 39 patients who underwent OG. Comparisons were based on clinicopathologic characteristics, surgical outcomes, and long-term survival rates. Comparison of LG and OG revealed no significant differences in the clinicopathologic characteristics. Five patients in the LG group and eight in the OG group showed a Child–Turcotte–Pugh score (CTPs) over A. In surgical outcomes, we observed shorter operation times (191.4 ± 63.9 vs. 225.9 ± 77.1 min, p = 0.039), reduced estimated blood loss (175.5 ± 214.1 vs. 396.9 ± 514.8 ml, p = 0.021), and shorter hospital stays (10.4 ± 4.6 vs. 13.7 ± 5.8 days, p = 0.008) in LG than OG. Regarding postoperative morbidity, 7 (19.4%) and 10 (25.6%) complications were observed in the LG and OG groups, respectively. There was no difference in complications between the two groups regardless of the CTPs. One patient with a CTPs of C succumbed to hepatic failure following LG. Long-term survival and overall and recurrence-free survival rates did not differ between the two groups. Even in cases with CTPs B, LG with lymph node dissection for gastric cancer patient was safer and acceptable than OG was. Therefore, LG can be considered an alternative surgical approach in gastric cancer with LC.

Hospital volume is known to be a crucial factor in reducing postoperative morbidity and mortality in laparoscopic gastrectomy for gastric cancer. However, it is unclear whether surgeon’s individual experience can overcome the effect of hospital volume. Clinicopathologic data of initial 50 laparoscopic gastrectomy cases were collected from six gastric cancer surgeons. Half of the six surgeons worked in high-volume centers, and the other half worked in low-volume hospitals. Perioperative outcomes were compared between the high-volume centers and the low-volume hospitals. Three low-volume hospitals in this study contained significantly more male and older patients with a higher American Society of Anesthesiologists score than high-volume centers. Although high- and low-volume hospitals mainly used laparoscopy-assisted and totally laparoscopic approach, respectively, there were no differences between the two groups in the extent of resection, operating time, estimated blood loss, and number of collected lymph nodes. Postoperative recovery such as duration to soft diet and hospital stay did not differ between the high- and the low-volume hospitals. No significant difference was found in postoperative morbidities by Clavien–Dindo classification. There was no mortality reported in both groups of the enrolled hospitals. Hospital volume is not a decisive factor in affecting postoperative morbidity and mortality for well-trained beginners in laparoscopic surgery for gastric cancer.

We evaluated the feasibility of a three-port totally laparoscopic distal gastrectomy (TLDG) as a reduced port laparoscopic surgery for the treatment of early gastric cancer (EGC).In total, 110 patients who underwent three-port TLDG (n = 25) and four-port TLDG (n = 85) were enrolled. A propensity score matching analysis was used to compensate for the differences between the groups in age, gender, body mass index, Eastern Cooperative Oncology Group classification, and comorbidity. After the matching, operative details, pathological features, and short-term postoperative outcomes were compared between groups.By propensity score matching, 25 matched pairs were created, and no characteristic difference was observed between the groups. Operating time was significantly shorter in the three-port TLDG group than in the four-port TLDG group (139.4 ± 39.4 minutes versus 184.8 ± 42.1 minutes, respectively; P .001). Duration until discharge was significantly shorter in the three-port TLDG group than in the four-port TLDG group (8.2 ± 5.6 days versus 10.2 ± 6.6 days, respectively; P .046). Regarding pathological features, including TNM stage, no significant difference was observed between the groups.The three-port TLDG is a practical method as a reduced port surgery and has better short-term outcomes than the four-port TLDG for the treatment of EGC.

Objective Surgeons' interest and participation in endoscopy have increased recently. The aims of the present study were to assess the learning curve for surgical training in upper endoscopy and to suggest an appropriate training program for surgeons in Korea. Design Under the supervision of skilled endoscopists, 4 trainees who participated in this study performed more than 150 esophagogastroduodenoscopy procedures, according to the recommendations of the American Society for Gastrointestinal Endoscopy. The success of the procedures was defined as the fulfillment of designated time and checkpoints. A cumulative sum model was used to assess the learning curve. Results During the same period, the 4 trainees completed 158, 160, 166, and 180 procedures, respectively. Plateau points occurred on the learning curve at the 81st, 90th, 98th, and 111th case in the cumulative sum model and the mean value of the plateau was the 95th case. Conclusions An intensive education tool and training module that meets the conditions of surgical residents is mandatory for the training of proficient surgical endoscopists.