D2 Gastrectomy Research Articles

Laparoscopic D2 plus complete mesogastrium excision using the "enjoyable space" approach versus conventional D2 total gastrectomy for local advanced gastric cancer: short-term outcomes.

IntroductionLaparoscopy-assisted radical total gastrectomy is technically demanding.AimTo introduce the “enjoyable space” approach to achieve D2 plus complete mesogastrium excision (CME) and to investigate its safety and feasibility.Material and methodsBetween January 2015 and December 2017, 165 patients with primary advanced upper gastric cancer underwent laparoscopy-assisted radical total gastrectomy. Among these patients, 81 underwent conventional D2 total gastrectomy (D2 group) and 84 underwent D2 plus CME total gastrectomy (D2 + CME group). Clinicopathological characteristics, surgical outcomes and postoperative complications were compared between the two groups.ResultsThere were no significant differences between the two groups (p > 0.05) in clinicopathological characteristics. However, the D2 + CME group had a longer mean operative time, lower mean blood loss and slightly higher mean number of retrieved lymph nodes (LNs) than the D2 group (p < 0.05 each). The mean time to first flatus, liquid diet, and soft diet and the duration of hospital stay were similar between the two groups (p > 0.05 each). No significant difference in postoperative complication rates was found between the groups (16.0% vs. 9.5%, p > 0.05).ConclusionsThe “enjoyable space” approach is an option to achieve D2 + CME, and its safety and feasibility over conventional method are confirmed with lower intraoperative blood loss and more harvested LNs.

Role of D2 gastrectomy in gastric cancer with clinical para-aortic lymph node metastasis

BACKGROUNDOwing to the technical difficulty of pathological diagnosis, imaging is still the most commonly used method for clinical diagnosis of para-aortic lymph node metastasis (PALM) and evaluation of therapeutic effects in gastric cancer, which leads to inevitable false-positive findings in imaging. Patients with clinical PALM may have entirely different pathological stages (stage IV or not), which require completely different treatment strategies. There is no consensus on whether surgical intervention should be implemented for this group of patients. In particular, the value of D2 gastrectomy in a multidisciplinary treatment (MDT) approach for advanced gastric cancer with clinical PALM remains unknown.AIMTo investigate the value of D2 gastrectomy in a MDT approach for gastric cancer patients with clinical PALM.METHODSIn this real-world study, clinico-pathological data of all gastric cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2011 and 2016 were reviewed to identify those with clinically enlarged PALM. All the clinico-pathological data were prospectively documented in the patient medical record. For all the gastric cancer patients with advanced stage disease, especially those with suspicious distant metastasis, the treatment methods were determined by a multidisciplinary team.RESULTSIn total, 48 of 7077 primary gastric cancer patients were diagnosed as having clinical PALM without other distant metastases. All 48 patients received chemotherapy as the initial treatment. Complete or partial response was observed in 39.6% (19/48) of patients in overall and 52.1% (25/48) of patients in the primary tumor. Complete response of PALM was observed in 50.0% (24/48) of patients. After chemotherapy, 45.8% (22/48) of patients received D2 gastrectomy, and 12.5% (6/48) of patients received additional radiotherapy. The postoperative major complication rate and mortality were 27.3% (6/22) and 4.5% (1/22), respectively. The median overall survival and progression-free survival of all the patients were 18.9 and 12.1 mo, respectively. The median overall survival of patients who underwent surgical resection or not was 50.7 and 12.8 mo, respectively. The 3-year and 5-year survival rates were 56.8% and 47.3%, respectively, for patients who underwent D2 resection. Limited PALM and complete response of PALM after chemotherapy were identified as favorable factors for D2 gastrectomy.CONCLUSIONFor gastric cancer patients with radiologically suspicious PALM that responds well to chemotherapy, D2 gastrectomy could be a safe and effective treatment and should be adopted in a MDT approach for gastric cancer with clinical PALM.

Correlation of CHAF1A with adjuvant chemotherapy outcome and microsatellite instability in gastric cancer.

e15511 Background: Clinical outcomes of adjuvant chemotherapy in gastric cancer (GC) have considerable stage-independent variability, which underscores the need for predictive molecular markers. Previous studies indicated that CHAF1A played a critical role in tumor growth, but whether it was associated with adjuvant chemotherapy in GC was still unknown. This retrospective study investigated the prognostic value of CHAF1A in adjuvant chemotherapy of GC. Methods: A total of 325 stage IB-III patients with fluoropyrimidines (FU)-based adjuvant chemotherapy after curative D2 gastrectomy meeting eligibility criteria were selected. CHAF1A protein expression was determined by immunohistochemical method. The primary outcomes were Overall survival (OS) and Disease-free survival (DFS). Kaplan-Meier method was used to estimate survival curve and Cox model for multifactor analysis. Results: CHAF1A mRNA was overexpressed in GC tissues and positive CHAF1A protein expression was not associated with OS and DFS in overall patients treated by FU-based chemotherapy ( P = 0.391 and 0.511, respectively). However, as stratified by tumor sites, positive CHAF1A expression was associated with poor OS and DFS in non-cardia cancer ( P = 0.009 and 0.007, respectively) but not in cardia cancer ( P = 0.229 and 0.112, respectively). Multivariate analysis indicated that CHAF1A expression level was still an independent predictor for both OS (HR = 2.42; 95% CI: 1.12-5.20; P = 0.024) and DFS (HR = 1.91; 95% CI: 1.03-3.54; P = 0.039) in non-cardia GC. Furthermore, CHAF1A was correlated with the status of microsatellite instability ( P = 0.025). Conclusions: CHAF1A might be a predictor for outcomes of FU-based adjuvant chemotherapy in patients with non-cardia GC, but needed further prospective studies to confirm.

Is it worthy of adding dissection of the superior mesenteric vein lymph node (14v) to standard D2 gastrectomy for distal gastric cancers with No. 6 lymph node metastasis?

Radical gastrectomy with D2 lymphadenectomy has been widely recognized as standard surgical procedure for advanced gastric cancer, while the role of No. 14v lymphadenectomy in distal gastric cancer remains controversial. Clinicopathological data of 793 distal gastric cancer patients who underwent at least a radical D2 lymphadenectomy with No. 6 nodes metastasis were retrospectively reviewed. Fifty patients received No. 14v lymphadenectomy. Patients with No. 14v nodes metastasis (21/50, 42.0%) had poor prognosis. The No. 14v nodes metastasis was not an independent prognostic factor (P = 0.075). In distal gastric cancer patients with No. 6 nodes metastasis, No. 14v lymphadenectomy deteriorated overall survival, what's more, No. 14v lymphadenectomy was an independent risk prognostic factor (hazard ratio: 1.404; 95% confidence interval 1.043-1.889; P = 0.025). There was no significant difference in overall or locoregional and other types of recurrence rate between the 14vD+ and the 14vD- groups. The proportion of complication rate was greater in 14vD+ group (P = 0.001). Extended D2 gastrectomy including No. 14v lymphadenectomy seems to be associated with poor overall survival and increased complication rate of distal gastric cancer patients with No. 6 nodes metastasis.

Survival Benefit of Neoadjuvant Chemotherapy with S-1 Plus Docetaxel for Locally Advanced Gastric Cancer: A Propensity Score-Matched Analysis

BackgroundPostoperative docetaxel plus S-1 (DS) chemotherapy is expected to be the standard therapeutic strategy for pStage III gastric cancer based on the results of the JACCRO GC-07 study. Neoadjuvant chemotherapy (NAC) is thought to have several advantages over adjuvant settings.ObjectiveThis study aimed to compare the efficacies of NAC DS and the surgery-first strategy for advanced gastric cancer patients with D2 gastrectomy.MethodsThis was a retrospective, single-institution observational study. Of 171 patients with locally advanced (cStage IIB or III) gastric cancer who underwent curative D2 gastrectomy and received NAC DS and/or S-1 adjuvant chemotherapy between 2011 and 2017, 76 (after propensity score matching for 132 patients who met the eligibility criteria) were enrolled in this study. The 3-year progression-free survival (PFS) rate was used to directly compare efficacies between NAC DS patients and surgery-first patients.ResultsThe 3-year PFS rates for the NAC DS group were significantly higher than those for the surgery-first group (80.0 vs. 58.7; p = 0.037), and the progression hazard ratio of the NAC DS group compared with the surgery-first group was 0.394 (95% confidence interval 0.159–0.978; p = 0.045).ConclusionsThe NAC DS group showed a high 3-year PFS compared with the surgery-first group, with standard S-1 postoperative chemotherapy or observation. NAC DS can be expected to be beneficial as the standard therapy for advanced gastric cancer and should be adopted for the test arm of a randomized controlled phase III trial.

Clinical significance of CD8+ T cell immunoreceptor with Ig and ITIM domains+ in locally advanced gastric cancer treated with SOX regimen after D2 gastrectomy

ABSTRACTGastric cancer (GC) development and progression is significantly associated with tumour immune escape. T cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibits T-cell responses and is associated with human cancers and T cell exhaustion phenotypes, but its role in cancers remains unclear. TIGIT and programmed cell death protein (PD)-1 levels were detected in 441 human GC specimens using histochemistry. We used flow cytometry to evaluate percentage of TIGIT+ constituting CD8+ T cells of 23 patients with GC who underwent D2 gastrectomy and the S-1 plus oxaliplatin (SOX) regimen. We investigated the influence of SOX regimen and TIGIT functional antibody on CD8 tumour-infiltrating lymphocytes (TILs). Results showed that PD-1 and TIGIT were significantly over expressed in GC and predicted poorer outcome, agreeing with bioinformatics analysis. Significantly reduced percentages of CD8+ TIGIT+ cells were observed in patients after D2 gastrectomy (pre- vs post-surgery, 38 ± 8.7% vs. 26.7% ± 5.2%, p < 0.0001). TIGIT expression on CD8+T cells was modulated by chemotherapeutics (pre- and post-chemotherapy, 31.3 ± 9% vs. 25.1 ± 4.5%, respectively, p = 0.0047) and higher TIGIT expression in post-chemotherapy group was associated with relapsed GC (p = 0.036). In vitro experiments revealed increased CD8+ TIL proliferation and interferon (IFN)-γ production following SOX regimen and TIGIT functional antibody treatments. In conclusion, TIGIT contributes to CD8+ TILs immune dysfunction in patients with GC. Combination of anti-TIGIT therapy and chemotherapy could be considered a therapy for GC.

Combined Surgery and Extensive Intraoperative Peritoneal Lavage vs Surgery Alone for Treatment of Locally Advanced Gastric Cancer

Peritoneal metastasis is the most frequent pattern of postoperative recurrence in patients with gastric cancer. Extensive intraoperative peritoneal lavage (EIPL) is a new prophylactic strategy for treatment of peritoneal metastasis of locally advanced gastric cancer; however, the safety and efficacy of EIPL is currently unknown. To evaluate short-term outcomes of patients with advanced gastric cancer who received combined surgery and EIPL or surgery alone. From March 2016 to November 2017, 662 patients with advanced gastric cancer receiving D2 gastrectomy were enrolled in a large, multicenter, randomized clinical trial from 11 centers across China. In total, 329 patients were randomly assigned to receive surgery alone, and 333 patients were randomly assigned to receive surgery plus EIPL. Clinical characteristics, operative findings, and postoperative short-term outcomes were compared between the 2 groups in the intent-to-treat population. Short-term postoperative complications and mortality. The present analysis included data from 550 patients, 390 men and 160 women, with a mean (SD) age of 60.8 (10.7) years in the surgery alone group and 60.6 (10.8) in the surgery plus EIPL group. Patients assigned to the surgery plus EIPL group exhibited reduced mortality (0 of 279 patients) compared with those assigned to surgery alone (5 of 271 patients [1.9%]) (difference, 1.9%; 95% CI, 0.3%-3.4%; P = .02). A significant difference in the overall postoperative complication rate was observed between patients receiving surgery alone (46 patients [17.0%]) and those receiving surgery plus EIPL (31 patients [11.1%]) (difference, 5.9%; 95% CI, 0.1%-11.6%; P = .04). Postoperative pain occurred more often following surgery alone (48 patients [17.7%]) than following surgery plus EIPL (30 patients [10.8%]) (difference, 7.0%; 95% CI, 0.8%-13.1%; P = .02). Inclusion of EIPL can increase the safety of D2 gastrectomy and decrease postoperative short-term complications and wound pain. As a new, safe, and simple procedure, EIPL therapy is easily performed anywhere and does not require any special devices or techniques. Our study suggests that patients with advanced gastric cancer appear to be candidates for the EIPL approach. ClinicalTrials.gov identifier: NCT02745509.

Outcomes of preoperative S-1 and docetaxel combination chemotherapy in patients with locally advanced gastric cancer.

The therapeutic outcomes of stage III gastric cancer patient receiving D2 gastrectomy and adjuvant chemotherapy remain unsatisfactory. To improve the long-term outcomes in this population, the combination of docetaxel and S-1 (DS) therapy can be expected to be a useful regimen as neoadjuvant chemotherapy (NAC). This study aimed to prospectively evaluate the efficacy of NAC-DS for clinical stage III gastric cancer. Between January 2010 and December 2013, 26 patients were enrolled. Patients with clinical stage III gastric cancer received two courses of docetaxel 40mg/m2 on day 1, 15 and S-1 40mg/m2 bid orally on day 1-7, 15-21 every 4 weeks, followed by radical D2 gastrectomy. Short- and long-term outcomes were evaluated. This study was approved by the ethics committee of Yokohama City University, and was registered in the University Hospital Medical Information Network (UMIN) database (ID: 000011521). Of 26 patients, 24 (92.3%) patients completed two courses of NAC. After NAC-DS, Grade 3 neutropenia was observed in 5 (19.2%) patients including one patient with febrile neutropenia, anemia in 1 (3.8%) patient and diarrhea in 1 (3.8%) patient. All patients underwent R0 gastrectomy and pathological response was found in 15 (57.6%) patients. Postoperatively, Clavien-Dindo grade II complication occurred in 8 (30.7%) patients and no mortality was observed. The 5-year overall survival (OS) was 57.7%, median OS was 78.7months and recurrence free survival (RFS) was 49.0%, median RFS was 45.4months with 66.5months median follow-up. Pathological response (HR = 0.091, 95% CI 0.011-0.730, p = 0.016) and > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for recurrence, > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for overall survival by multivariate analysis. NAC-DS demonstrated acceptable toxicity with a high R0 resection rate in clinical stage III gastric cancer patients, especially in patients with good nutritional status. Further prospective study is warranted to compare the long-term outcomes between with and without NAC-DS.

Timing and site-specific trends of recurrence in patients with pathological stage II or III gastric cancer after curative gastrectomy followed by adjuvant S-1 monotherapy.

Adjuvant S-1 monotherapy prolongs the survival of patients with pathological stage II or III gastric cancer undergoing D2 gastrectomy. This therapeutic regimen is standard in Japan. Unfortunately, some patients who undergo this treatment suffer from recurrent disease. However, information regarding the timing and site-specific trends of recurrence is insufficient. Among 396 patients who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy between 2008 and 2012, 122 experienced a recurrence. We retrospectively determined the timing and sites of recurrence. The median RFS of the 122 patients was 19.5 months, and their 1-, 3- and 5-year RFS rates were 67.2%, 23.0% and 5.7%, respectively. There were no significant differences in RFS among disease substages. Local recurrence, lymph node involvement and peritoneal and hematogenous metastases were found in 6, 25, 63 and 42 patients, respectively. Approximately 10% of patients presented with contemporaneous sites of recurrence. Local recurrence and lymph node metastasis plateaued 3years after gastrectomy. Peritoneal and hematogenous metastasis increased within 5years after surgery. In patients with hematogenous metastasis, the number of liver metastases plateaued but increased in others. In patients with recurrent disease who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy, 80% of recurrences occur within 3years after gastrectomy. The timing of recurrence is not significantly different among substages. Although the rates of local recurrence and lymph node and liver metastasis plateau after 3 years, peritoneal and the other hematogenous metastases increase within 5years.

Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501)

The prognosis of patients with linitis plastica (type 4) and large (≥ 8cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer.

93 Background: Neoadjuvant chemotherapy is promising to improve the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both active for metastatic gastric cancer. Methods: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and docetaxel/cisplatin/S-1 (DCS) using a two-by-two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or schirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 eligible patients in total so that the treatment group with the superior observed 3-year OS rate by more than 60% as compared with 50% of the control group was to be selected with a probability of 85% or higher. Results: Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). The 3-year OS was 58.1% (95% CI, 45.8-70.3%) in CS and 60.0% (95% CI, 48.0-71.9%) in DCS with hazard ratio of 0796 (95% CI, 0.475-1.335), while that was 53.1% (95% CI, 40.9-65.4%) in the two courses and 65.0% (95% CI, 53.2-76.8%) in the four courses with hazard ratio of 0.722 (95% CI, 0.429-1.216). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% (95% CI, 45.8-70.3%) both for two and four courses in CS, while that was 48.5% (95% CI, 31.4-65.5%) for two courses of DCS and was 71.9% (95% CI, 56.3-87.5%) for four courses of DCS. Conclusions: Considering high 3-year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer. Clinical trial information: UMIN000006378.

Subgroup analysis of JCOG0501 phase III study to confirm superiority of additional neoadjuvant chemotherapy with S-1 plus cisplatin to D2 gastrectomy with S-1 adjuvant chemotherapy for resectable type IV or large type III gastric cancer.

110 Background: We previously reported that the superiority of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin was not demonstrated for schirrhous or similar macroscopic type (type 4 or large type 3) gastric cancer. However, overall survival (OS) in both arms was better than previous reports (3-year OS: 62.4% in gastrectomy plus adjuvant S-1 [arm A] and 60.9% in NAC followed by gastrectomy plus adjuvant S-1 [arm B]). Therefore, we explored whether histology and peritoneal cytology are associated with treatment effect. Methods: After staging laparoscopy, a total of 300 eligible patients with clinically resectable disease were randomized to arm A, or arm B. In this report, treatment effect was explored in key subgroups such as histology and peritoneal cytology using the data from JCOG0501. Cox regression model was used to investigate the interaction between arms and subgroups. Results: Hazard ratio (HR) classified by histology (excluding one missing) was 0.686 (95% CI: 0.414-1.138) for non-signet type (n = 123) and 1.158 (95% CI: 0.805-1.666) for signet type (n = 176) (p = 0.098 for interaction). HR by peritoneal cytology was 0.870 (95%CI: 0.616-1.228) for the negative (n = 240) and 1.051 (95% CI: 0.598-1.845) for the positive (n = 60) (p = 0.513 for interaction). 3 year-OS of signet ring cell histology was 63.2% (95% CI: 52.2-72.4) in arm A and 51.7% (95% CI: 40.9-61.5) in arm B, that of non-signet ring cell histology was 62.3% (95% CI: 48.9-73.1) in arm A and 74.2% (95% CI: 61.4-83.3) in arm B, and that of peritoneal cytology positive was 35.7% (95% CI: 18.9-53.0) in arm A and 25.0% in arm B (95% CI: 11.8-40.7), and that of peritoneal cytology negative was 68.6% (95% CI: 59.5-76.1) in arm A and 70.6% (95% CI: 61.5-77.9) in arm B. Conclusions: NAC might be beneficial for non-signet ring cell histology. Considering the survival results, primary surgery followed by S-1 could be recommended for this disease even though histology was signet ring cell type or peritoneal cytology was positive. Clinical trial information: UMIN000000279.

Laparoscopy-assisted versus open D2 distal gastrectomy for advanced gastric cancer: Five year overall survival and morbidity results from a randomized phase II multicenter clinical trial (COACT 1001).

Background: For advanced gastric cancer (AGC), D2 gastrectomy is the standard treatment. However, a laparoscopic D2 gastrectomy(LG) is technically challenging surgery. Our previous report of COACT 1001 study, which is randomized phase II study to evaluate the feasibility of LG compared with open surgery(OG) for AGC, showing primary endpoint of non-compliance of lymph node dissection and three-year disease-free survival supported role of LG for AGC. Herein we report five-year overall and disease-free survival outcome of the study.

Techniques and Current Role of Sentinel Lymph Node (SLN) Concept in Gastric Cancer Surgery.

Gastric cancer patients represent a rather divergent patient group and in certain carefully selected cases of early forms of gastric cancer the D2 gastrectomy could be considered a more radical procedure than the biological and oncological characteristics of the primary tumor on the gastric wall would require. As any unnecessary dissection increases morbidity without always respective survival benefits, an approach that could accurately predict and actually dictate the exact extent of lymph node dissection would be ideal. It is more than logical the assumption that the standard D2 lymphadenectomy could represent an overtreatment in distinct patients groups such as patients with early gastric cancer with favorable pathological characteristics and clinically negative nodes not suitable for endoscopic treatment because this early stage disease shows limited lymph node metastasis incidence and excellent overall survival. Considering that the D2 gastrectomy has a negative impact on the quality of life of gastric cancer patients due to the post-gastrectomy functional results, a concept of a more targeted lymph node dissection, when appropriate, is certainly appealing. It is yet to be proven whether sentinel lymph node navigation surgery can fulfill such expectations providing the appropriate balance between morbidity and oncological safety in selected gastric cancer patients.

Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer.

Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs.Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy.Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance.Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series.

Оценка безопасности комплексного лечения (пролонгированная неоадъювантная химиолучевая терапия в режиме гиперфракционирования с последующей гастрэктомией D2) при местно-распространённом раке желудка

Оценка безопасности комплексного лечения (пролонгированная неоадъювантная химиолучевая терапия в режиме гиперфракционирования с последующей гастрэктомией D2) при местно-распространённом раке желудка

Ten Thousand Consecutive Gastrectomies for Gastric Cancer: Perspectives of a Master Surgeon.

As radical gastrectomy with lymph node dissection is currently the best strategy to cure gastric cancer, the role of the surgeon remains quite important in conquering it. Dr. Sung Hoon Noh, a surgeon and surgical oncologist specializing in gastric cancer, has treated gastric cancer for 30 years and has conducted over 10000 cases of gastrectomy for gastric cancer. He first adapted an electrocautery device into gastric cancer surgery and has led standardization of surgical procedures, including spleen preserving gastrectomy. His procedures based on patient-oriented insights have become the basis of the concept of enhanced recovery after surgery. He has also contributed to improving patient's survival through adoption of a multidisciplinary approach: he proved the benefit of adjuvant chemotherapy after radical D2 gastrectomy for stage II/III gastric cancer in clinical trials, updating treatment guidelines throughout the world. Dr. Noh also opened the era of precision medicine for treating gastric cancer, as he developed and validated a mRNA expression based algorithm to predict prognosis and response to chemotherapy. This article reviews his contribution and long history of service in the field of gastric cancer. The perspectives of this master surgeon, based on his profound experience and insights, will outline directions for integrative multidisciplinary health care and how can surgeons prepare for the future.

Early-stage outcomes of bursectomy in surgery of gastric cancer and radical gastric resection

Aim: Bursectomy, mainly defined as a complete dissection of the peritoneal lining covering the anterior plane of the transverse mesocolon and the pancreas with an omentectomy during gastrectomy, has been performed for the serosa-positive gastric cancers. Recently, some researchers have interrogated whether bursectomy for gastric cancer is essential from a surgical point of view, thus, we aimed to investigate the short-term surgical and early-stage clinicopathological outcomes of bursectomy in the treatment of advanced gastric cancer patients by a single center study and retrospective controlled trial. Material and Methods: From January 2016 to December 2017, retrospective findings of selected 100 gastric cancer patients in advanced tumor stages and underwent D2 radical gastrectomy were grouped and analyzed in terms of bursectomy performed or not in Bakirkoy Dr. Sadi Konuk Training and Research Hospital.Results: In conclusion, 50 patients were in bursectomy (B) group and 50 patients in non-bursectomy (NB) group. Clinical features (age, gender, and gastrectomy pattern and tumor location) of both groups showed no statistically significant difference. Postoperative mortality rate were also similar of both groups (4%). All other post-operative complications were not significantly distinctive for two groups. Conclusions: Bursectomy may increase the surgical duration of D2 gastrectomy and but not early-stage outcomes and post-operative complications. Experienced surgeons can perform the procedure safely. However, long-term, large sample sized, and high-quality randomized controlled trials are needed for the survival benefits of bursectomy.

TOTAL OMENTECTOMY IN GASTRIC CANCER SURGERY: IS IT ALWAYS NECESSARY?

ABSTRACTBackground: Traditionally, total omentectomy is performed along with gastric resection and extended lymphadenectomy in gastric cancer (GC) surgery. However, solid evidences regarding its oncologic benefit is still scarce. Aim: To evaluate the incidence of metastatic omental lymph nodes (LN) in patients undergoing curative gastrectomy for GC, as well as its risk factors and patients’ outcomes. Methods: All consecutive patients submitted to D2/modified D2 gastrectomy due to gastric adenocarcinoma from March 2009 to April 2016 were retrospectively reviewed from a prospective collected database. Results: Of 284 patients included, five (1.8%) patients had metastatic omental LN (one: pT3N3bM0; two: pT4aN3bM0; one: pT4aN2M0 and one pT4bN3bM0). Four of them deceased and one was under palliative chemotherapy due relapse. LN metastases in the greater omentum significantly correlated with tumor’s size (p=0.018), N stage (p<0.001), clinical stage (p=0.022), venous invasion growth (p=0.003), recurrence (p=0.006), site of recurrence (peritoneum: p=0.008; liver: p=0.023; ovary: p=0.035) and death (p=0.008). Conclusion:The incidence of metastatic omental LN of patients undergoing radical gastrectomy due to GC is extremely low. Total omentectomy may be avoided in tumors smaller than 5.25 cm and T1/T2 tumors. However, the presence of lymph node metastases in the greater omentum is associated with recurrence in the peritoneum, liver, ovary and death.

Impact of intra-peritoneal fat distribution on intra-operative bleeding volume with D2 lymphadenectomy in Chinese patients with gastric cancer

To explore the quantitative measurements and evaluation of intra-peritoneal fat distribution by MDCT and its significance in predicting intra-operative bleeding volume during D2 lymphadenectomy in gastric cancer (GC) patients. From June 2016 to September 2017, GC patients scheduled for open gastrectomy with D2 lymph-node dissection were enrolled. According to the BMI, the subjects were then classified as normal BMI(BMI<25kg/m2); overweight (BMI=25-30 kg/m2) and obese (BMI≥30kg/m2). According to the intraoperative blood loss (IBL), the patients were further separated into high IBL (IBL; ≥ 300ml) or low IBL (<300ml). Clinicopathological parameters between the groups were statistically compared and univariate and multivariate analysis were used to identify predictive factors such as intra-peritoneal fat areas (IFA) and intra-peritoneal fat areas ratio (IFAR) for high IBL. A total of 226 patients were included in the study where 53 patients underwent distal while 173 underwent total gastrectomy. According to the BMI classification, there were 25 normal BMI, 108 overweight and 25 obese subjects. According to the IBL, there were 98 high IBL and 128 low IBL subjects. IFA and IFAR were significantly greater in the high IBL group than in the low IBL group. There was no significant difference in any other clinicopathological factors between the high IBL group and the low IBL group. Multivariate analysis revealed that high IFA and IFAR independently predicted high IBL. The use of MDCT to evaluate the precise distribution of abdominal fat during preoperative examination can prompt surgeons to develop techniques to decrease intraoperative bleeding in obese patients. Nevertheless, it is yet necessary to be surgically more meticulous when dealing with patients with high IFA or high IFA/IFAR in order to improve the outcome of D2 gastrectomy.