The Effectiveness of Screening Total Colonoscopy for Preoperative Patients with Gastric Cancer.

BACKGROUND: Colorectal cancer (CRC) is the most common cancer that coincides with gastric cancer (GC). Although the usefulness of total colonoscopy (TCS) as a CRC screening tool has been reported in preoperative patients with GC, the long-term outcome of patients with synchronous CRC (SCRC) remains unclear. This study aims to clarify the significance of preoperative screening TCS for GC in terms of survival outcomes. PATIENTS AND METHODS: We included 796 patients who underwent preoperative screening TCS for GC. The risk factors, clinicopathological features, and survival outcome of SCRC were examined. Furthermore, the cost-effectiveness was evaluated from the perspective of improving the rates of mortality caused by CRC. RESULTS: SCRC was observed in 43 patients (5.4%). Endoscopic treatment for SCRC was performed on 30 patients. In total, 15 patients underwent surgical resection, including 2 patients requiring additional surgery after endoscopic treatment. Regarding pathological stages, 25 patients had stage 0, 12 patients had stage I, 5 patients had stage II, and 1 patient had stage IIIB disease. The cumulative mortality rates were as follows: GC-related deaths, 12.6%; deaths from cancers other than CRC, 1%; deaths from other causes, 5.5%. No deaths were attributed to SCRC. Comparing the patients who did not undergo TCS, an incremental cost-effectiveness ratio analysis suggested that a screening cost of 5.86 million yen was required to prevent one CRC death. CONCLUSIONS: Curative treatment was possible in all patients with SCRC. No deaths were attributed to SCRC, suggesting that screening TCS for GC is effective.

Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer.

BACKGROUND: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. METHODS: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. RESULTS: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. CONCLUSIONS: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry stomach cancer subcohort.

BACKGROUND: The Cancer-VTE Registry was a large-scale, multicenter, prospective registry designed to investigate real-world data on venous thromboembolism (VTE) incidence and risk factors in adult Japanese patients with solid tumors. This pre-specified subgroup analysis aimed to estimate the incidence of VTE, including VTE types other than symptomatic VTE, and identify risk factors of VTE in stomach cancer from the Cancer-VTE Registry. METHODS: Stage II-IV stomach cancer patients who planned to initiate cancer therapy and underwent VTE screening within 2 months before registration were enrolled. RESULTS: Of 1,896 patients enrolled, 131 (6.9%) had VTE at baseline, but 96.2% were asymptomatic. Female sex, age ≥ 65 years, VTE history, and D-dimer > 1.2 µg/mL were independent risk factors of VTE at baseline. Notably, patients with D-dimer > 1.2 µg/mL at the time of cancer diagnosis had an approximately 20-fold risk of VTE. During follow-up, event incidences were symptomatic VTE, 0.3%; incidental VTE requiring treatment, 1.1%; composite VTE, 1.4%; bleeding, 1.6%; cerebral infarction/transient ischemic attack/systemic embolic events, 0.7%; and all-cause death, 15.0%. The incidence of all-cause death was higher in patients with VTE vs without VTE at baseline (adjusted hazard ratio 1.67; 95% confidence interval 1.21-2.32; p = 0.002). CONCLUSIONS: VTE prevalence at the time of cancer diagnosis was not negligible and was extremely high when the patients had high D-dimer. VTE screening by D-dimer before starting cancer treatment is advisable, even for asymptomatic patients, regardless of whether the patient is undergoing surgery or chemotherapy. TRIAL REGISTRATION: UMIN000024942.

Molecular profile of poorly cohesive gastric carcinoma with special reference to survival.

BACKGROUND: Patients with poorly cohesive gastric carcinoma (PCC) are known to have poor survival. However, detailed molecular biology of PCC has not been elucidated, except for mutations in CDH1 and RHOA. Additionally, the molecular profiles of signet-ring cell carcinoma (SRC) have not been fully investigated. We aimed to investigate the association between molecular profiles and survival in PCC and PCC subtypes. METHODS: The present study included 455 patients with gastric adenocarcinoma underwent radical gastrectomy. Whole-exome sequencing and gene expression profiling were conducted. Patients were classified according to the WHO classification as PCC or non-PCC, with PCC being further classified into SRC, combined, and PCC not-otherwise-specified (NOS). Clinicopathological factors and survival were compared with molecular profiles. RESULTS: Of the patients, 159 were classified with PCC, while 296 were classified with non-PCC. Among PCC, 44 were classified with SRC, 64 with combined, and 51 with PCC-NOS. Mutations in CDH1 and RHOA were remarkably more frequent in PCC than in non-PCC. PCC had worse overall survival (OS) and disease-specific survival (DSS) compared to non-PCC. For PCC, the SRC group had good OS and DSS, whereas PCC-NOS classification with CDH1 mutations was associated with extremely poor survival. In the PCC-NOS and combined groups, patients with mutations in the extracellular domain 1 of CDH1 had poor survival. CONCLUSIONS: Our findings suggest that PCC has poorer survival than non-PCC. Accumulation of CDH1 and RHOA mutations are unique profiles in PCC. Among PCC, CDH1 mutations may play a crucial role in the survival of non-SRC PCC.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE.

BACKGROUND: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy. METHODS: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification). RESULTS: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort. CONCLUSIONS: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery.

Comparisons of surgical outcomes between robotic and laparoscopic total gastrectomy in patients with clinical stage I/IIA gastric cancer.

BACKGROUND: The robotic approach is especially promising for challenging surgeries, such as total gastrectomy. However, it remains unclear whether robotic total gastrectomy (RTG) is superior to conventional laparoscopic total gastrectomy (LTG). The present study aimed to clarify the impact of RTG on short- and long-term outcomes for patients with clinical stage I/IIA gastric cancer. METHODS: This study included 98 patients with clinical stage I/IIA gastric cancer who underwent minimally invasive total gastrectomy from October 2013 to December 2020 at the Shizuoka Cancer Center. The short- and long-term outcomes of RTG were compared with those of LTG. RESULTS: This study included 36 RTG and 58 LTG patients. RTG was associated with a significantly longer operative time than LTG (p = 0.023). All complications tended to be lower in the RTG group than in the LTG group (2.8% and 15.5%, respectively; p = 0.083). There were no patients with anastomotic leakage in the RTG group. The multivariate analysis identified LTG as the only independent risk factor for postoperative complications (odds ratio, 6.620; 95% confidence interval, 1.132-126.4; p = 0.034). The survival of the RTG and LTG groups was equivalent. CONCLUSIONS: RTG reduced the risk of complications compared to LTG. Patients treated using the two approaches showed equivalent survival.

Advantages of a robotic approach compared with laparoscopy gastrectomy for patients with high visceral fat area.

BACKGROUND: Gastric cancer surgery for obese patients is regarded as a technically challenging procedure. The morbidity after gastrectomy has been reported to be significantly higher in patients with high visceral fat area (VFA). Robotic gastrectomy (RG) is expected to be advantageous for complicated operations. However, whether RG is superior to conventional laparoscopic gastrectomy (LG) for patients with visceral fat obesity remains unclear. The present study aimed to clarify the impact of RG on the short- and long-term outcomes of patients with high VFAs. METHODS: This study included 1306 patients with clinical stage I/II gastric cancer who underwent minimally invasive gastrectomy between January 2012 and December 2020. The patients were subclassified according to VFA. The short- and long-term outcomes of RG were compared with those of LG in two VFA categories. RESULTS: This study included 394 (high-VFA, 151; low-VFA, 243) and 882 patients (high-VFA, 366; low-VFA, 516) in the RG and LG groups, respectively. RG was associated with a significantly longer operative time than LG (high-VFA, P < 0.001; low-VFA, P < 0.001). The incidence rates of overall and intra-abdominal infectious complications in the high-VFA patients were lower in the RG group than in the LG group (P = 0.019 and P = 0.048, respectively) but not significantly different from those in the low-VFA patients. In the multivariate analysis, LG was identified as the only independent risk factor of overall (odds ratio [OR] 3.281; P = 0.012) and intra-abdominal infectious complications (OR 3.462; P = 0.021) in the high-VFA patients. The overall survival of high-VFA patients was significantly better in the RG group than in the LG group (P = 0.045). CONCLUSIONS: For patients with visceral fat obesity, RG appears to be advantageous to LG in terms of reducing the risk of complications and better long-term survival.

Prognostic factors in patients who received paraaortic lymph node dissection for locally advanced gastric cancer with extensive lymph node metastasis.

PURPOSE: While paraaortic lymph node (PAN) dissection (PAND) has been found to be efficacious for patients with extensive lymph node metastasis (ELM) of locally advanced gastric cancer (LGC), the optimal indications for PAND remain to be elucidated. Thus, the prognostic factors among these patients were evaluated. METHODS: A total of 35 patients with ELM of LGC who underwent gastrectomy with D2 and PAND between August 2008 and December 2019 were included and evaluated for long-term outcomes and prognostic factors. RESULTS: Preoperative chemotherapy was administered to 33 patients [neoadjuvant chemotherapy (NAC), n = 26; palliative chemotherapy followed by conversion surgery, n = 7], none of whom suffered surgical mortality. The pathological analysis identified PAN metastasis in 11 patients (31.4%). The 5-year overall and relapse-free survival (RFS) survival were 66.4% and 52.6%, respectively. Locoregional recurrence was found in one patient. The multivariate analysis revealed that NAC (P = 0.011) and < 3 metastatic PANs on preoperative imaging (P = 0.017) were independently associated with RFS. CONCLUSION: D2 and PAND after NAC can be a promising approach for patients with ELM of LGC. In particular, patients with a limited number of metastatic PANs can be considered good candidates for PAND.

Endoscopic submucosal dissection versus surgery in elderly patients with early gastric cancer of relative indication for endoscopic resection.

OBJECTIVES: Surgery is recommended for early gastric cancer (EGC) beyond the endoscopic resection (ER)-indication for the risk of lymph node metastasis; however, ER may be chosen as a "relative ER-indication" considering age and comorbidities. This study aimed to compare outcomes of endoscopic submucosal dissection (ESD) only and surgery (primary surgery and additional surgery after non-curative ESD) among elderly patients with relative ER-indication EGC and to further assess prognostic factors. METHODS: Outcomes of ESD and surgery (417 cases; 114 ESD, 303 surgery) in elderly patients (≥75 years) with relative ER-indication EGC were retrospectively analyzed. Prognostic factors were also examined. RESULTS: During the observation period (median; ESD, 34 months; surgery, 61 months), 29% of ESD and 35% of surgery patients died, including 4% and 5% from gastric cancer (GC), respectively. ESD showed lower overall survival (OS) than surgery (P = 0.027) but comparable disease-free survival (P = 0.916). OS-associated factors were age and prognostic nutritional index (PNI) in males (age ≥79, hazard ratio [HR] 2.21, P = 0.001; PNI <45, HR 2.06, P = 0.031) and age in females (age ≥82, HR 4.06, P = 0.004). Treatment was not a prognostic factor in either subgroup. Pathological category ≥pT1b2 (submucosal invasion ≥500 µm) and lymphovascular invasion (LVI) were significantly associated with GC death (mortality: ≥pT1b2, 7.7%, P = 0.002; LVI, 10.1%, P < 0.001). CONCLUSIONS: In elderly patients with relative ER-indication EGC, ESD may have comparable long-term efficacy to surgery, and treatment selection had a minor contribution to OS. For patients with poor preoperative prognostic factors, diagnostic ESD may be performed first, followed by additional surgery based on pathological results.

Discrepancy between endoscopic and pathological ulcerative findings in clinical intramucosal early gastric cancer.

BACKGROUND: Ulcerative finding (UL) is one of the factors that define the indication and curability of endoscopic resection (ER) in early gastric cancer (EGC). Discrepancies between endoscopic UL (cUL) and pathological UL (pUL) sometimes occur in clinical practice. The aim of this study was to investigate the discrepancy rate in UL diagnosis and the risk factors associated with such discrepancies. METHODS: Patients with clinical intramucosal (cT1a) EGC who underwent ER or surgery between September 2002 and December 2017 were analyzed. The proportion of cUL-negative (cUL0) lesions that were identified as pUL-positive (pUL1) and that of cUL-positive (cUL1) lesions that were identified as pUL-negative (pUL0) were calculated. Logistic regression analysis was performed to estimate the associations between discrepancy in UL diagnosis and clinical variables of the lesion, such as the size, histology, location, and macroscopic type. RESULTS: In total, 5382 lesions were evaluated; 5.5% of cUL0 lesions (256/4619) were identified as pUL1, while 38.7% of cUL1 lesions (295/763) were pUL0. Multivariate analysis indicated that in cUL1 lesions, tumor location in the lower third of the stomach (odds ratio 3.11, 95% confidence interval 1.90-5.08) was identified as an independent risk factor for overestimation. CONCLUSIONS: Endoscopic diagnosis of UL in cT1a EGC was overestimated in 38.7% of lesions, especially for lesions located in the lower third of the stomach. This discrepancy should be considered in the management of cT1a EGC with UL.

Efficacy of minimally invasive distal gastrectomy for elderly patients with clinical stage I/IIA gastric cancer: a propensity-score matched analysis.

BACKGROUND: Phase III trials have shown the non-inferiority of minimally invasive distal gastrectomy (MIDG) comparison with open distal gastrectomy (ODG) in patients with gastric cancer; however, it remains unclear whether MIDG is also effective in the elderly. This study aimed to clarify the efficacy of MIDG in elderly gastric cancer patients. PATIENTS AND METHODS: This study included 316 patients older than 75 years with clinical stage I/IIA gastric cancer who underwent distal gastrectomy from August 2008 to December 2016 at the Shizuoka Cancer Centre. The long-term outcomes between MIDG and ODG were compared after propensity score matching. RESULTS: After propensity score matching, there were 97 patients each in the MIDG and ODG groups, with an improved balance of confounding factors between the two groups. MIDG was associated with significantly longer operative time and a lower level of blood loss than ODG. The incidence of complications was comparable between the two groups. Survival outcomes were better in the MIDG group than in the ODG group (overall survival; P = 0.034, relapse-free survival; P = 0.027). In the multivariable analysis, ODG [hazard ratio (HR) 1.971, P = 0.046], being 80 years or older (HR 2.285, P = 0.018), male sex (HR 2.428, 95% P = 0.024), and poor physical status (HR 2.324, P = 0.022) were identified as independent prognostic factors for overall survival. CONCLUSIONS: We found that MIDG showed better efficacy than ODG in elderly gastric cancer patients. MIDG is an acceptable option for elderly patients.

Long-term outcomes of robotic gastrectomy for clinical stage I gastric cancer: a single-center prospective phase II study.

INTRODUCTION: The outcomes of robotic gastrectomy (RG) for gastric cancer remain unclear due to a lack of prospective studies. We had previously designed and conducted a prospective phase II study of RG that showed favorable short-term outcomes. Herein, we aimed to determine the long-term outcomes of RG for clinical stage I gastric cancer. PATIENTS AND METHODS: This single-center, prospective phase II study enrolled patients with clinical stage I gastric cancer undergoing RG. The survival outcomes, which were the secondary endpoints of the study, were evaluated. RESULTS: Between December 2012 and April 2015, 120 patients were enrolled in this study. The 5-year overall survival (OS) was 96.7% (95% confidence interval [CI] 91.5-98.7%). The 5-year recurrence-free (RFS) and disease-specific survival (DSS) rates were 96.7% (95% CI 91.5-98.7%) and 99.2% (95% CI 94.3-99.9%), respectively. When confining the analysis to distal and pylorus-preserving gastrectomy, the 5-year OS, RFS, and DSS were 98.1% (95% CI 92.7-99.5%), 98.1% (95% CI 92.7-99.5%), and 100%, respectively. Only one patient died due to relapse of gastric cancer, while three died from other causes. CONCLUSIONS: Long-term outcomes of RG was comparable to those of open and laparoscopic gastrectomy when the surgeries were performed by experienced surgeons in a high-volume center.

The Effect of Minimally Invasive Gastrectomy for Gastric Cancer on Postoperative Gallstone Formation.

BACKGROUND: Gallstones are known to occur quite frequently after gastrectomy. Most of the studies about postoperative cholelithiasis have focused on open gastrectomy, whereas laparoscopic gastrectomy has recently gained popularity as a type of minimally invasive surgery (MIS). Hence, the efficacy of MIS in preventing post-gastrectomy gallstone formation remains to be elucidated. This study aimed to evaluate the risk of gallstone formation after MIS for clinical stage I/IIA gastric cancer. METHODS: A total of 1166 patients undergoing gastrectomy for clinical stage I/IIA gastric cancer between 2009 and 2016 were included in this study. Gallstones were detected on abdominal ultrasound and/or computed tomography. Multivariate logistic regression analysis was used to determine factors associated with postoperative gallstone formation. RESULTS: Gallstone formation was observed in 174 patients (15%), of whom 22 (2%) experienced symptomatic cholelithiasis. In multivariate analysis, the following were identified as risk factors for post-gastrectomy gallstone formation: open approach with an odds ratio (OR) of 1.670 and a 95% confidence interval (CI) of 1.110-2.510 (P = 0.014), older age (OR 1.880; 95% CI 1.290-2.730; P < 0.001), high body mass index (OR 1.660; 95% CI 1.140-2.420; P = 0.008), Roux-en-Y (RY) reconstruction (OR 1.770; 95% CI 1.230-2.530; P = 0.002), hepatic branch vagotomy (OR 1.600; 95% CI 1.050-2.440; P = 0.029), and intra-abdominal infectious complications (OR 3.040; 95% CI 1.680-5.490; P < 0.001). CONCLUSION: Our study suggested that MIS along with the preservation of the hepatic vagus nerve and non-RY reconstruction could help prevent post-gastrectomy gallstone development.

Robotic Gastrectomy Compared with Laparoscopic Gastrectomy for Clinical Stage I/II Gastric Cancer Patients: A Propensity Score-Matched Analysis.

BACKGROUND: Robotic gastrectomy (RG) has been developed to address the drawbacks of laparoscopic gastrectomy (LG); however, whether or not RG is superior to conventional LG remains to be seen. The present study aimed to clarify the impact of RG on clinical stage I/II gastric cancer patients. METHODS: The present study included 1208 patients with clinical stage I/II gastric cancer who had minimally invasive gastrectomy from January 2012 to March 2020 at the Shizuoka Cancer Center. The short- and long-term outcomes of RG and LG were compared after propensity score matching. RESULTS: This study involved 835 LG and 345 RG patients. After propensity score matching, there were 342 patients each in the RG and LG groups, with an improved balance of confounding factors between the two groups. RG was associated with a significantly longer operative time and lower amylase concentration in the drainage fluid on the first postoperative day than LG. Furthermore, the incidence of intra-abdominal infectious complications in the RG was lower than that in the LG (4.4% vs. 9.4%; P = 0.015). The survival of the RG and LG groups was equivalent. CONCLUSIONS: RG reduced the risk of intra-abdominal infectious complications in comparison with LG in the propensity score-matched analysis. Patients treated by the two approaches showed equivalent survival.

Preserving a Replaced Left Hepatic Artery Arising from the Left Gastric Artery During Laparoscopic Distal Gastrectomy for Gastric Cancer.

BACKGROUND: A replaced left hepatic artery (RLHA) arising from the left gastric artery (LGA) is occasionally encountered during laparoscopic gastrectomy. Although the RLHA is usually divided at the root level as RLHA preservation might result in inadequate lymph node dissection, blood flow disruption by RLHA division may lead to hepatic ischemia. To date, there is no consensus on RLHA preservation. Thus, we aimed to evaluate the efficacy of RLHA preservation by investigating the short-term outcomes of patients with RLHA who underwent laparoscopic distal gastrectomy (LDG). METHODS: A total of 106 patients with an aberrant LHA from the LGA were identified as having gastric cancer and underwent LDG from 2012 to 2018. Finally, 55 patients were retrospectively diagnosed with RLHA by preoperative computed tomography and included in this study. Patients were classified into the divided (n = 18) or preserved (n = 37) group. Clinicopathological factors and surgical outcomes were compared between the two groups. RESULTS: The RLHA preservation rate in patients who had been preoperatively diagnosed with RLHA was 88%. No significant difference was found in the number of harvested lymph nodes between the groups. The incidence of hepatic infarction was significantly higher in the divided group (16.7% vs. 0%, p = 0.031). Moreover, RLHA division caused postoperative transaminase elevation and was an independent risk factor for postoperative transaminase elevation (odds ratio: 55.8, p < 0.001). CONCLUSIONS: Surgical procedures of RLHA preservation reduced postoperative transaminase elevation and hepatic infarction in patients who underwent LDG. Surgeons should confirm the RLHA preoperatively and preserve it to prevent hepatic damage.

A Randomized Phase II Study to Evaluate Prolonged Prophylactic Antibacterial Drug Treatment for Patients with Elevated Drain Amylase Concentration After Gastrectomy with D2 Lymph Node Dissection (REDUCED2).

INTRODUCTION: After D2 gastrectomy for advanced gastric cancer, patients with a high drainage fluid amylase level (d-AMY) on the first postoperative day (1POD) have an especially high risk of severe abdominal infectious complications (AICs), which could be fatal. On the hypothesis that prolonged antibiotic administration could reduce the incidence of severe AICs, we conducted a randomized phase II study to evaluate the optimal treatment duration of prophylactic antibiotics for patients who underwent D2 gastrectomy and had elevated d-AMY on 1POD. METHODS: Patients whose d-AMY was >3000 IU/L on 1POD after D2 gastrectomy for gastric cancer were randomly assigned to normal prophylactic antibiotic treatment given only on the day of surgery (Group A) or to prolonged antibiotic treatment given for 1 week after surgery (Group B). The primary endpoint was the incidence of severe AICs (Clavien-Dindo grade IIIa or higher). This trial was registered as UMIN000012152. RESULTS: This study was started in December 2013 and stopped in February 2019 because of poor patient accrual. Finally, 35 and 37 patients were assigned to groups A and B, respectively. The incidences of AICs were 22.9% (eight of 35) in group A and 13.5% (five of 37) in group B. One-sided P value of the Fisher exact test was 0.234. No adverse reactions to antibiotic prophylaxis were observed in any of the patients. CONCLUSIONS: Prolonged prophylactic antibiotic administration had a marginal benefit in preventing grade III or higher AICs and caused no treatment-related morbidities.

Prediction of S-1 adjuvant chemotherapy benefit in Stage II/III gastric cancer treatment based on comprehensive gene expression analysis.

BACKGROUND: Studies to identify predictive biomarkers of adjuvant chemotherapy with S-1 after gastrectomy in Stage II/III gastric cancer patients have been done; however, more clarity and understanding are needed. Our aim in the present study was to identify biomarkers predicting benefit due to S-1 adjuvant chemotherapy using comprehensive gene expression analysis. METHODS: We retrospectively analyzed 102 patients receiving adjuvant chemotherapy with S-1 and 46 patients not receiving S-1 adjuvant chemotherapy after gastrectomy for gastric cancer treatment between January 2014 and December 2016. Hierarchical clustering analysis was performed based on the gene expression data obtained using cDNA microarray. Differentially expressed genes (DEGs) were identified using thresholds of absolute fold changes of > 4.0 and a false discovery rate P value of < 0.01. Gene Ontology (GO) analysis and GO network visualization were performed using the ClueGO app in Cytoscape. RESULTS: Hierarchical clustering analysis in patients treated with S-1 adjuvant chemotherapy revealed two clusters with favorable and unfavorable survival outcomes. We identified 147 upregulated DEGs and 192 downregulated DEGs in the favorable outcome group. GO analysis to identify significantly upregulated genes showed enrichment in immune-related genes and GO terms. Upregulation of these immune-related genes was not associated with survival in patients not receiving S-1 adjuvant chemotherapy. CONCLUSIONS: The upregulation and enrichment of immune-related genes and GO terms may be predictive biomarkers in patients who would benefit from adjuvant S-1 chemotherapy to treat Stage II/III gastric cancer.

Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence.

BACKGROUND: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. METHODS: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. RESULTS: Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, ß-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified ß-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001). CONCLUSIONS: The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. ß-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.

Obesity is a risk factor for internal hernia after laparoscopic or robot-assisted gastrectomy with mesenteric defect closure for gastric cancer.

BACKGROUND: Internal hernia (IH) is a life-threatening complication after gastrectomy. The increase in the frequency of minimally invasive surgery is considered to be related to the increase in the frequency of IH, and mesenteric defect closure has been recommended to reduce this complication. However, IH can occur even when mesenteric defects are closed, so the risk of IH in the patients with mesenteric closure remains uncertain. We attempted to clarify the risk factors for IH in these patients. METHODS: From 2013 to 2017, we retrospectively reviewed 310 patients with gastric cancer who underwent laparoscopic or robot-assisted gastrectomy with Roux-en-Y (RY) or double-tract (DT) reconstruction with mesenteric defect closure. Univariate and multivariate analyses were performed to identify the risk factors. RESULTS: The incidence of IH was 1.3% (n = 4). A preoperative body mass index (BMI) ≥ 25 kg/m2 (p = 0.044), postoperative chemotherapy (p = 0.034), and body weight loss rate at 6 months ≥ 15% (p = 0.045) were risk factors for IH on a univariate analysis. A multivariate analysis showed that a BMI at the time of surgery of ≥ 25 kg/m2 was an independent risk factor for IH (odds ratio = 11.9, p = 0.049). CONCLUSIONS: Preoperative obesity is an independent risk factor for IH after minimally invasive gastrectomy followed by RY or DT reconstruction with mesenteric defect closure. We need to conduct vigilant follow-up for IH, especially in these patients.