Is Total Omentectomy Mandatory in T3 and T4a Gastric Cancer for Laparoscopic Distal Gastrectomy?

BACKGROUND: Despite the lack of strong evidence, total omentectomy (TO) remains the recommended procedure for gastric cancer (GC) for T3 or deeper tumors. Partial omentectomy (PO) has recently become a preferred procedure owing to its simplicity during laparoscopic distal gastrectomy (LDG); however, the oncological role of PO needs to be elucidated. METHODS: Overall, 341 patients with T3 or T4a GC who had undergone LDG between 2009 and 2016 were divided into TO (n = 167) and PO (n = 174) groups. Propensity matching was performed with respect to covariance age, sex, T and N stage, tumor size, and degree of tumor differentiation. Clinicopathological characteristics and long-term follow-up data were analyzed for both groups. RESULTS: After successful propensity matching, both groups included 107 patients. In a matched cohort, no significant difference in clinicopathologic features and short-term surgical outcomes was observed between the two groups. Furthermore, no significant difference in relapse-free survival (RFS; p = 0.201) and peritoneal seeding-free survival (PSFS; p = 0.094) was observed. However, tumor recurrence as peritoneal metastasis occurred in 5 (4.7%) patients in the PO group and 13 (12.1%) patients in the TO group. In Cox proportional hazards analysis, omentectomy was not identified as a significant factor for RFS, PSFS, and overall survival; however, advanced N and T4a stage were considered significant factors for RFS and PSFS, respectively. CONCLUSIONS: PO may be adopted during the LDG of T3 or T4a GC without definite gross serosal exposure. More large-scale evidence or prospective study is recommended.

Predictive model for long-term weight recovery after gastrectomy for gastric cancer: an introduction to a web calculator.

BACKGROUND: Weight changes after gastrectomy affect not only quality of life but also prognosis and survival. However, it remains challenging to predict the weight changes of individual patients. Using clinicopathological variables, we built a user-friendly tool to predict weight change after curative gastrectomy for gastric cancer. METHODS: The clinical data of 984 patients who underwent curative gastrectomy between 2009 and 2013 were retrospectively reviewed and analyzed. Multivariate logistic regression was performed to identify variables predictive of postoperative weight change. A nomogram was developed and verified via bootstrap resampling. RESULTS: Age, sex, performance status, body mass index, extent of resection, pathological stage, and postoperative weight change significantly influenced postoperative weight recovery. Postoperative levels of hemoglobin, albumin, ferritin and total iron-binding capacity were significant covariates. The nomogram performed well (concordance index = 0.637); calibration curves indicated appropriate levels of agreement. We developed an online weight prediction calculator based on the nomogram ( http://gc-weightchange.com/en/front/ ). CONCLUSIONS: The novel, Web-calculator based on the predictive model allows surgeons to explore patient weight patterns quickly. The model identifies patients at high risk for weight loss after gastrectomy; such patients require multidisciplinary medical support.

Refining gastric cancer staging: examining the interplay between number and anatomical location of metastatic lymph nodes - a retrospective multi-institutional study.

BACKGROUND: The current gastric cancer staging system relies on the number of metastatic lymph nodes (MLNs) for nodal stage determination. However, incorporating additional information such as topographic status may help address uncertainties. This study evaluated the appropriateness of the current staging system and relative significance of MLNs based on their anatomical location. METHODS: Patients who underwent curative gastrectomy for gastric cancer between 2000 and 2019 at six Catholic Medical Center-affiliated hospitals were included. Lymph node-positive patients were classified into the perigastric (stations 1-6, group P) or extragastric (stations 7-12) groups. The extragastric group was further subdivided into the near-extragastric (stations 7-9, group NE) and far-extragastric (stations 10-12, group FE) groups. RESULTS: We analyzed the data of 3,591 patients with positive lymph node metastases. No significant survival differences were found between group P and the extragastric group in each N stage. However, in N1 and N2, group FE showed significantly worse survival than the other groups (p = 0.013 for N1, p < 0.001 for N2), but not in N3. In the subgroup analysis, group FE had a significantly lower overall survival in N2, regardless of the cancer location. CONCLUSIONS: Our large-scale multi-institutional big data analysis confirmed the superiority of the current numerical nodal staging system for gastric cancer. Nonetheless, in N1 and N2 in which there is an upper limit on metastatic nodes, attention should be paid to the potential significance of topographic information for specific nodal stations.

Impact of postoperative NSAIDs (IV-PCA) use on short-term outcomes after laparoscopic gastrectomy for the patients of gastric cancer.

BACKGROUND: Further data are necessary to evaluate the risk of complications associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) postoperatively. This study aimed to determine the correlation between the use of NSAIDs in intravenous patient-controlled analgesia (IV-PCA) and postoperative complications after laparoscopic gastrectomy in patients with gastric cancer. METHODS: This retrospective, single-center study was conducted. The study population comprised 2150 patients who underwent laparoscopic gastrectomy for gastric cancer treatment. They were divided into two groups: non-NSAIDs (n = 1215) and NSAIDs (n = 935) according to their use of the drugs. Clinicopathologic characteristics, operative details, postoperative complications within 30 days, risk factors for complications, and survival were analyzed. RESULTS: Of the 2150 patients, 935 (43.49%) used NSAIDs. The overall complication rate showed no significant difference between the NSAIDs and non-NSAIDs groups (22.7% vs. 20.7%, p = 0.280), while the rates of anastomotic leakage and duodenal leakage were higher in the NSAID group (2.4% vs. 0.7%, p = 0.002 and 1.8% vs. 0.6%, p = 0.007, respectively). The rates of intra-abdominal bleeding and intra-abdominal abscess were significantly higher in the NSAID group (2.1% vs. 0.7%, p = 0.005 and 1.5% vs. 0.4%, p = 0.008, respectively). However, postoperative ileus occurred more frequently in the non-NSAID group (3.0% vs. 1.4%, p = 0.015). On multivariate analysis, NSAID use was an independent risk factor for early postoperative complications (1.303 [1.042-1.629], p = 0.020). Meanwhile, the NSAID group showed no differences in overall survival at each pathological stage. CONCLUSION: Postoperative NSAID use by IV-PCA is associated with anastomotic leakage, duodenal stump leakage, intra-abdominal bleeding, and intra-abdominal abscess in patients who underwent laparoscopic gastrectomy for gastric cancer. Caution is advised when NSAIDs are used peri-operatively.

The First Systematic Gastroscopy Training Program for Surgeons in Korea.

BACKGROUND: Endoscopic evaluation of the stomach is essential for preoperative planning and post-surgical surveillance for various diseases of the stomach, including malignancy. The gastroscopy education program for surgeons is currently in its infancy and is not systematically organized in Korea. This study aimed to introduce the first systematic gastroscopy education program for surgeons in Korea. METHODS: The gastroscopy education program entitled "Gastroscopy School for Surgeons (GSS)" comprised of theoretical education, dry lab hands-on training, and clinical practice. All participants were beginners without any gastroscopy experience. Clinical practice started after the completion of the theoretical and dry lab training. The gastroscopy practices utilized simple luminal observation, biopsy, localization using clips or dye injection, and limited therapeutic gastroscopy. The educational performances and surveys from 33 participants were analyzed. RESULTS: The participants consisted of surgical residents, general surgeons, gastrointestinal-specialized surgeons, and physicians. Participants performed a total of 2,272 gastroscopies, 2,008 of which were post-gastrectomy cases. Currently, of the 33 participants, 7 (21.2%) of the participants performed gastroscopy regularly, and 7 (21.2%) occasionally. According to the self-reported survey, one participant assessed their current gastroscopic technique to be at the expert level, and 25 (75.8%) at a proficient level. All participants considered gastroscopy education for surgeons to be necessary, and 28 (84.8%) stated that systematic education is not currently provided in Korea. CONCLUSION: We introduced the first systematic gastroscopy education program for surgeons in Korea, namely the GSS, which is practical and meets clinical needs. More training centers are needed to expand gastroscopy training among Korean surgeons.

Appropriate Number of Adjuvant Chemotherapy Cycles for Patients with Stage 2 or 3 Gastric Cancer After Curative Gastrectomy: A Multicenter Cohort Study.

BACKGROUND: Few studies have presented evidence pertaining to the adequate minimum number of adjuvant chemotherapy (AC) cycles required to achieve an oncologic benefit for gastric cancer. METHODS: From January 2012 to December 2013, data from patients who underwent curative radical gastrectomy and consequently received AC for pathologic stage 2 or 3 gastric cancer at 27 institutions in South Korea were analyzed. RESULTS: The study enrolled 925 patients, 661 patients (71.5%) who completed 8 cycles of AC and 264 patients (28.5%) who did not. Compared with the mean disease-free survival (DFS) of the patients who completed 8 AC cycles (69.3 months), the mean DFS of patients who completed 6 AC cycles (72.4 months; p = 0.531) and those who completed 7 AC cycles (63.7 months; p = 0.184) did not differ significantly. However, the mean DFS of the patients who completed 5 AC cycles (48.2 months; p = 0.016) and those who completed 1-4 AC cycles (62.9 months; p = 0.036) was significantly lower than the DFS of those who completed 8 AC cycles. In the multivariate Cox proportional hazards analysis, the mean DFS was significantly affected by advanced stage, large tumor size, positive vascular invasion, and number of completed AC cycles (1-5 cycles: hazard ratio 1.45; 95% confidence interval 1.01-2.08; p = 0.041). CONCLUSION: The current multicenter observational cohort study showed that the mean DFS for 6 or 7 AC cycles was similar to that for 8 AC cycles as an adjuvant treatment for gastric cancer.

Surveillance Endoscopy Guidelines for Postgastrectomy Patients Based on Risk of Developing Remnant Gastric Cancer.

BACKGROUND: Remnant gastric cancer (RGC) has a major impact on the long-term survival of postgastrectomy patients. In this study, we established surveillance endoscopy guidelines for postgastrectomy patients based on the risk of RGC. PATIENTS AND METHODS: A total of 6365 patients who underwent gastrectomy at Seoul St. Mary's Hospital from September 2005 to June 2018 were retrospectively reviewed; 85 patients were identified as having RGC. We divided the RGC patients into subgroups according to the interval between primary and secondary gastrectomy. RESULTS: The curative resection rate was significantly lower in patients with an interval of ≤ 5 years versus > 5 years (p = 0.017). RGC developed more frequently after Billroth II reconstruction, and at the anastomotic site, in patients with a > 10- versus ≤ 10-year interval (p = 0.006 and p = 0.014, respectively). Similar results were observed based on the 15-year interval cutoff (p = 0.001 and 0.018, respectively). The 5-year overall survival rate of patients with a ≤ 5-year interval was significantly lower than that of patients with a > 5-year interval (60.0% versus 85.7%, p = 0.015), while overall survival did not differ between the ≤ 10- and > 10-year, or ≤ 15- and 15-year interval groups. RGC incidence showed a decrease after around 20 years postoperatively. CONCLUSIONS: Thorough endoscopic examination should be conducted for up to 5 years postgastrectomy. Routine annual endoscopic follow-up should be performed for up to 20 years after the primary operation for gastric cancer, to allow for early detection of RGC.

Negative Impact of Endoscopic Submucosal Dissection on Short-Term Surgical Outcomes of Subsequent Laparoscopic Distal Gastrectomy for Gastric Cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) for gastric cancer produces an artificial ulcer, and negative effects on the surgical outcomes of additional gastrectomy after ESD are anticipated. The aim of this study is to analyze the effect of ESD on subsequent laparoscopic radical gastrectomy procedures and to compare the surgical results of post-ESD patients with the control group using propensity score (PS) methods. PATIENTS AND METHODS: From 2013 to 2018, 1446 patients underwent totally laparoscopic distal gastrectomy in our center. Among these patients, the clinicopathological factors and short-term surgical outcomes of 107 patients who underwent ESD before surgery (the ESD group) were evaluated. A 1:4 PS matching and inverse probability weighting method was utilized to compare the short-term surgical outcomes of the ESD group with those of a matched control group. RESULTS: A longer operation time was required for the patients who underwent gastrectomy earlier than 24 days after ESD than for the patients who did not. Patients whose ulcer size, due to previous ESD, exceeded 4.6 cm required longer operation times and exhibited more intraoperative blood loss than patients whose ulcer size was small. In the PS matching analysis, patients who underwent distal gastrectomy within 24 days after ESD showed more frequent postoperative morbidity than non-ESD patients. CONCLUSIONS: ESD after laparoscopic distal gastrectomy is largely safe in terms of short-term surgical outcomes, but a short interval between the two procedures and a large ESD scar can make subsequent operation difficult.

The Relevance of Serosal Exposure Without Nodal Metastasis in Resectional Gastric Cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of in vitro driven expression signatures of CD133 stem cell marker and tumor stroma on clinical outcomes in gastric cancers.

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.

A multi-center prospective randomized controlled trial (phase III) comparing the quality of life between laparoscopy-assisted distal gastrectomy and totally laparoscopic distal gastrectomy for gastric Cancer (study protocol).

BACKGROUND: KLASS (the Korean Laparoendoscopic Gastrointestinal Surgery Study) is a time-honored study group that has established laparoscopic surgery for gastrointestinal disease in Korea and has performed some important studies for the rationale of laparoscopic gastrointestinal surgery. A multi-center RCT (randomized controlled trial) to compare the quality of life (QOL) of patients undergoing totally laparoscopic distal gastrectomy (TLDG) and laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer, named as KLASS 07, has been currently prepared in Korea. METHODS: Patients diagnosed as gastric cancer, with clinical stage IA (T1N0M0) or IB (T1N1M0 / T2N0M0) according to the 7th edition of the Americal Joint Committee on Cancer System, were randomized to receive either TLDG or LADG. For surgical quality control, the surgeons participating in this trial had to have performed at least 50 gastrectomies and at least 30 gastrectomies annually (regardless of open or laparoscopic surgery for gastric cancer). The patients who are allocated to TLDG group undergo intracorporeal anastomosis and those who are assigned to LADG undergo extracorporeal anastomosis for gastrointestinal reconstruction. DISCUSSION: Thirty-one surgeons from 26 institutions were engaged in this trial. The primary endpoint is 30-day morbidity, and secondary endpoint is QOL assessed by the questionnaire score. The KLASS 07 trial is the first multi-center RCT to investigate whether there are significant and quantifiable differences between the QOL of TLDG and LADG. The findings from this trial are expected to be the critical clues for designing the detailed procedures during laparoscopic surgery for gastric cancer. TRIAL REGISTRATION: The protocol of KLASS 07 (CKLASS 01) was registered in http://register.clinicaltrials.gov as NCT03393182 (Date of registration: January 2nd, 2018.).

Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage.

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).

Mutation heterogeneity between primary gastric cancers and their matched lymph node metastases.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer.

BACKGROUND: Our goal was to evaluate changes in PD-L1 expression in primary tumours of metastatic gastric cancer before and after chemotherapy. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Borrmann Type 1 Cancer is Associated with a High Recurrence Rate in Locally Advanced Gastric Cancer.

BACKGROUND: 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. METHODS: Between January 1989 and December 2013, 1949 patients with advanced gastric cancer who underwent curative gastrectomy at our institution were enrolled in the study. RESULTS: 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. CONCLUSIONS: 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.

Efficacy of Adjuvant S-1 Versus XELOX Chemotherapy for Patients with Gastric Cancer After D2 Lymph Node Dissection: A Retrospective, Multi-Center Observational Study.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Adjuvant XELOX chemotherapy was more effective than S-1 for patients with stage 3B or 3C gastric cancer after D2 lymph node dissection.

Prognostic value of Dickkopf-1 and ß-catenin expression in advanced gastric cancer.

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 < 0.001). The combined expression of DKK1 and ß-catenin was significantly associated with high N stage (N2 and N3) (P = 0.042). In addition, patients with high DKK expression demonstrated poorer overall (OS) (P < 0.001) and disease-free survival (DFS) (P = 0.001). However, there were no differences between high DKK1 expression with ß-catenin positivity and high DKK1 expression with ß-catenin negativity (OS, P = 0.379: DFS, P = 0.255). Multivariate analysis revealed that high DKK1 alone or high DKK1 with ß-catenin positivity were independent prognostic factors for both OS (high DKK1: hazard ratio [HR], 2.130; 95% confidence interval [CI]; 1.370-3.312, P = 0.001; high DKK1 with ß-catenin positivity: HR, 2.140; 95% CI, 1.343-3.409: P = 0.001) and DFS (high DKK1: HR, 2.092; 95% CI, 1.180-3.708; P = 0.012; high DKK1 with ß-catenin positivity: HR, 2.357; 95% CI, 1.291-4.306; P = 0.005). CONCLUSION: Our results indicate that high DKK1 expression regardless of ß-catenin positivity is a crucial prognostic factor for predicting tumor recurrence and survival in patients with resected AGC.

Splenic Infarction as a Delayed Febrile Complication Following Radical Gastrectomy for Gastric Cancer Patients: Computed Tomography-Based Analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Radical Gastrectomy After Chemotherapy May Prolong Survival in Stage IV Gastric Cancer: A Korean Multi-institutional Analysis.

ABASTRACT: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Adjuvant surgery might improve the survival rate of patients with stage IV gastric cancer, particularly in R0 resection cases.