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.

Postoperative sarcopenia increases both gastric cancer and other-cause mortality in older adults undergoing radical gastrectomy for cancer.

BACKGROUND & AIMS: Preoperative sarcopenia in gastric cancer is associated with increased postoperative complications and reduced long-term survival. However, the association between postoperative sarcopenia and long-term outcomes remains unclear. Therefore, this study aims to clarify the association between sarcopenia after gastrectomy for gastric cancer and survival outcomes. METHODS: This retrospective study included 1512 patients aged ≥65 who underwent curative gastric resection for clinical stage I-III primary gastric cancer during 2008-2018. Sarcopenia was assessed preoperatively by measuring arm muscle area and grip strength, which was repeated 1 month after surgery. We compared the clinical characteristics, surgical treatments, and long-term outcomes between the postoperative normal and sarcopenia groups. RESULTS: Sarcopenia was observed in 173 and 305 patients pre- and postoperatively, respectively. Factors increasing the risk of postoperative sarcopenia included age of ≥75, lower preoperative body mass index, diabetes, and clinical stage II/III gastric cancer. Patients with postoperative sarcopenia after surgery had a significantly lower overall survival rate (hazard ratio [HR] 2.596, p < 0.001). Furthermore, postoperative sarcopenia was linked to decreased overall survival in patients with (HR 2.813, p = 0.002) and without (HR 1.925, p < 0.001) preoperative sarcopenia. Cumulative incidence showed significantly higher rates of deaths due to gastric cancer (HR 1.928, p < 0.001) and other causes (HR 2.736, p < 0.001) in the postoperative sarcopenia group. CONCLUSIONS: Postoperative sarcopenia in gastric cancer is linked to an increased risk of death due to cancer and other causes, underscoring the importance of perioperative sarcopenia management strategies.

Gastric inflammatory myofibroblastic tumor: a case report.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) of the stomach is an uncommon mesenchymal neoplasm. We present a case of gastric submucosal tumor (SMT) where the final diagnosis was IMT. CASE PRESENTATION: A 69-year-old man presented with a 24-mm SMT on the posterior wall of the middle third of the stomach that was detected by screening upper gastrointestinal endoscopy. Abdominal contrast-enhanced computed tomography showed that the tumor was well-enhanced. Although endoscopic ultrasonography-guided biopsy was performed, the histological diagnosis was not confirmed preoperatively. Since the tumor was clinically suspected to be a gastrointestinal stromal tumor, we performed gastric wedge resection by laparoscopic-endoscopic cooperative surgery. Pathologically, proliferative spindle cells with a positive reaction for smooth muscle actin, negativity for c-kit, desmin, s-100, CD34, STAT-6, ß-catenin and anaplastic lymphoma kinase 1 were identified. Hence, the tumor was finally diagnosed as an IMT originating from the stomach. CONCLUSIONS: When an SMT of the stomach is identified, the possibility of gastric IMT should be considered.

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 profiling of gastric neuroendocrine carcinomas.

Gastric neuroendocrine carcinoma (G-NEC) usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because common pathogenic mutations are shared. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis. We aimed to elucidate the tumorigenesis of G-NEC by focusing on the proportion of NEC components. Thirteen patients with G-NEC were included in this study. Comprehensive genetic analysis using whole-exome sequencing was performed. G-NEC without an adenocarcinoma component was defined as pure NEC. TP53 was detected as the most frequent gene mutation (85% of the patients), independent of classification. RB1, KMT2C, LTBP1, and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Pure NEC has different somatic mutation profile than other NECs. This study provides insights into the mechanism of tumorigenesis in G-NEC.

Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557-558 Deletion Mutations.

Gastrointestinal stromal tumors (GIST) with KIT exon 11 deletions involving in codons 557-558 (KIT Δ557-558) exhibit higher proliferation rates and shorter disease-free survival times compared with GISTs with other KIT exon 11 mutations. We analyzed 30 GIST cases and observed genomic instability and global DNA hypomethylation only in high-risk malignant GISTs with KIT Δ557-558. Whole-genome sequencing revealed that the high-risk malignant GISTs with KIT Δ557-558 (12 cases) had more structural variations (SV), single-nucleotide variants, and insertions and deletions compared with the low-risk, less malignant GISTs with KIT Δ557-558 (six cases) and the high-risk (six cases) or low-risk (6 cases) GISTs with other KIT exon 11 mutations. The malignant GISTs with KIT Δ557-558 showed higher frequency and significance in copy number (CN) reduction on chromosome arms 9p and 22q, and 50% of them had LOH or CN-dependent expression reduction in CDKN2A. In addition, SVs with driver potential were detected in 75% of them, in which AKT3 and MGMT were recurrently identified. Genome-wide DNA methylation and gene expression analyses showed global intergenic DNA hypomethylation, SNAI2 upregulation, and higher expression signatures, including p53 inactivation and chromosomal instability, as characteristics of malignant GISTs with KIT Δ557-558 that distinguished them from other GISTs. These genomic and epigenomic profiling results revealed that KIT Δ557-558 mutations are associated with increased genomic instability in malignant GISTs. Significance: We present genomic and epigenomic insights into the malignant progression of GISTs with KIT exon 11 deletions involving in 557-558, demonstrating their unique chromosomal instability and global intergenic DNA hypomethylation.

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.

Molecular genetic positioning of small intestine and papilla of Vater carcinomas including clinicopathological classification.

BACKGROUND: Small intestine carcinoma (SIC) cases in Japan have recently been treated with chemotherapy according to colorectal carcinoma classification, while papilla of Vater carcinoma (PVC) cases according to cholangiocarcinoma (CHC) classification. However, few research reports support the molecular genetic validity of these therapeutic choices. PATIENTS AND METHODS: Here, we investigated the clinicopathological and molecular genetic factors of SIC and PVC. We used the data from the Japanese version of The Cancer Genome Atlas. Additionally, molecular genetic data on gastric adenocarcinoma (GAD), colorectal adenocarcinoma (CRAD), pancreatic ductal adenocarcinoma (PDAC), and CHC were also referred to. RESULTS: This study consisted of tumor samples from 12 patients of SIC and three patients of PVC treated from January 2014 to March 2019. Among them, six patients had pancreatic invasion. t-Distributed stochastic neighbor embedding analysis showed that the gene expression pattern of SIC was similar not only to those of GAD and CRAD, but also to that of PDAC in the pancreatic invasion patients. In addition, PVC resembled the GAD, CRAD, and PDAC, rather than the CHC. The molecular genetic characteristics of the six patients with pancreatic invasion were: one had high microsatellite instability, two had a TP53 driver mutation, and three had tumor mutation burden values <1 mutation/Mb with no driver mutation. CONCLUSIONS: In this study, the extensive gene expression profiling of organ carcinomas newly suggests that SIC or PVC may resemble GAD, CRAD, and PDAC. In addition, the data demonstrate that pancreatic invasive patients may be classified into several subtypes using molecular genetic factors.

Report of two patients in whom comparisons of the somatic mutation profile were useful for the diagnosis of metastatic tumors.

BACKGROUND: When a patient has multiple tumors in different organs, it is very important to identify whether the tumors are multiple cancers or metastasis from one tumor in order to establish an optimal treatment strategy. However, it is difficult to obtain an accurate diagnosis from conventional diagnostic strategies, including immunohistochemistry. We report two patients with multiple tumors in which a somatic mutation comparison using next-generation sequencing (NGS) was useful for the diagnosis of a metastatic tumor. CASE PRESENTATIONS: Patient 1: A 64-year-old man was diagnosed with gastric and lung cancer. After radical chemoradiotherapy for lung cancer, gastrectomy was planned for gastric cancer. At gastrectomy, the patient underwent a multiple omics analysis for "Project HOPE". The gene mutational signature of the gastric tumor showed signature 4 of COSMIC mutational signature version 2, which was associated with smoking and has not been found in gastric cancer. To confirm that the gastric tumor was metastasis from lung cancer, we conducted a somatic mutation comparison of the two tumors with 409-gene panel sequencing, which revealed that 28 of 97 mutations in the lung tumor completely matched those of the gastric tumor. Based on these findings, the gastric tumor was diagnosed as metastasis from lung cancer. Patient 2: A 47-year-old woman underwent distal gastrectomy for gastric cancer. A colon tumor was detected 6 years after gastrectomy. The colon lesion was a submucosal tumor-like elevated tumor, and was suspected to be metastasis from gastric cancer. The patient underwent sigmoidectomy, and participated in "Project HOPE". The possibility of primary colon cancer could not be ruled out, and we conducted a somatic mutation comparison of the two tumors as we did with Patient 1. Panel sequencing revealed 11 mutations in the gastric tumors, 4 of which completely matched those of the colon tumor. The colon tumor was diagnosed as metastasis from gastric cancer. CONCLUSION: We reported two patients with multiple tumors in which a somatic mutation comparison using NGS was useful for the diagnosis of a metastatic tumor.

Detection of secondary upper gastrointestinal tract cancer during follow-up esophagogastroduodenoscopy after gastrectomy for gastric cancer.

Aim: Esophagogastroduodenoscopy (EGD) may contribute to early detection of secondary cancer in the upper gastrointestinal tract although the clinical relevance of follow-up after gastrectomy remains unclear. This study aimed to elucidate the effectiveness of follow-up EGD by investigating the incidence of secondary cancer in any part of the upper gastrointestinal tract. Methods: Data from 1438 patients who underwent curative partial gastrectomy for primary gastric cancer between 2008 and 2014 and follow-up EGD at least once during a 5-year follow-up period were retrospectively reviewed. Incidence rates of remnant gastric cancer, laryngeal cancer, and esophageal cancer detected after follow-up EGD were determined, and risk factors for secondary cancers were examined. The characteristics of clinicopathological diagnoses of secondary cancers were reviewed and compared according to the frequency of follow-up EGD. Results: The average annual frequency of EGD was 0.7, while the 5-year cumulative incidence rates of remnant gastric cancer and secondary laryngeal and esophageal cancers were 2.9% and 1.3%, respectively. Risk factors for remnant gastric cancer included heavy smoking, proximal gastrectomy, and tumor size ≥ 30 mm. All secondary cancers were resectable upon diagnosis, with endoscopically resectable cancer accounting for 81.0% of cases. Our results found a significantly higher proportion of endoscopically resectable cancers during regular follow-up than during infrequent follow-up. Conclusions: Follow-up EGD can be a useful modality for detecting secondary upper gastrointestinal tract cancer, likely leading to curative treatment for secondary cancer. Focusing on patients presenting with risk factors may increase the value of follow-up EGD after gastrectomy.

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.

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.

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.

The impact of pancreas compression time during minimally invasive gastrectomy on the postoperative complications in gastric cancer.

AIM: Pancreas compression during minimally invasive gastrectomy causes blunt injury to the pancreas and leads to postoperative complications. However, the extent of practical compression associated with the incidence of postoperative complications remains unknown. This study aimed to evaluate the impact of pancreas compression, particularly the duration of compression, on short-term outcomes in minimally invasive gastrectomy for gastric cancer. METHODS: This study included 178 patients who underwent laparoscopic or robotic gastrectomy at the Shizuoka Cancer Center in 2018. The total time of pancreas compression during gastrectomy was measured using video-reviews, and the correlation between the time and surgical outcomes was evaluated. RESULTS: A duration of 3 min was selected as the cutoff value of pancreas compression time to predict high drain amylase concentration on postoperative day 1 (≥1000 U/L). The incidence of clinically relevant pancreatic fistula (1.5% vs 12.4%, P = .011) and all postoperative complications (12.3% vs 30.1%, P = .010) were significantly higher in the longer-compression group than in the shorter-compression group. The multivariable analysis identified longer compression as the only independent risk factor for postoperative complications. CONCLUSION: More than a few minutes of pancreas compression during minimally invasive gastrectomy was associated with a higher incidence of postoperative complications.

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.

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.

Utility of a modified age-adjusted Charlson Comorbidity Index in predicting cause-specific survival among patients with gastric cancer.

INTRODUCTION: The current study aimed to evaluate the ability of a modified version of the age-adjusted Charlson Comorbidity Index (mACCI) in predicting cause-specific survival (CSS) among patients with gastric cancer who underwent curative gastrectomy and compared it with the conventional ACCI. MATERIALS AND METHODS: Patients who underwent gastrectomy for gastric cancer from 2007 to 2016 (n = 2885) were included. A mACCI was established by excluding scores for other malignancies, such as other cancers, leukemia, and lymphoma. After determining the optimal cutoff ACCI and mACCI values for CSS, clinicopathological factors and survival outcomes were assessed according to the ACCI and mACCI. RESULTS: Both ACCI and mACCI were identified as independent prognostic factors for overall survival (p < 0.001 and p < 0.001, respectively). However, only mACCI was identified as an independent prognostic factor for CSS (p < 0.001). The present study suggested that mACCI was a better indicator of CSS in patients with gastric cancer who underwent curative gastrectomy than ACCI. CONCLUSION: Our findings showed that the mACCI was a strong predictor of CSS in patients with gastric cancer who underwent curative gastrectomy. We believe that the mACCI will become a novel marker that would guide treatment decisions for patients with gastric cancer suffering from comorbidities.