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 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.

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.

Preventive effect on delayed gastric emptying of preserving the infra-pyloric vein in laparoscopic pylorus-preserving gastrectomy for early gastric cancer.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has the postoperative advantages of a better quality of life and less weight loss than distal gastrectomy. However, postoperative delayed gastric emptying (DGE) due to antral hypomotility can be a problem. Although preserving the infra-pyloric vein (IPV) is reported to improve congestion of the antrum and prevent DGE, the benefits of this procedure have not been confirmed. The present study aimed to clarify the preventive effect on DGE of preserving the IPV. METHODS: A total of 148 patients [IPV-preserved (IPVP): 78 patients and IPV-non-preserved (IPVN): 70 patients] who underwent laparoscopic and robotic PPG (LRPPG) for early gastric cancer were enrolled in this study. The clinicopathologic characteristics and incidence of DGE were compared between the groups. The nutritional risk index (NRI) at 1, 2, and 3 years after the operation and the relapse-free survival (RFS) were also compared. RESULTS: There were no significant differences in the clinicopathological characteristics between the two groups. DGE was observed in 15 of 148 patients (10.1%). The incidence of DGE did not differ markedly between the 2 groups (IPVP vs. IPVN; 11.5% vs. 8.6% p = 0.596). There were no significant differences in other complications between the groups either (IPVP vs. IPVN; 19.2% vs. 21.4%; p = 0.838). The NRI and 3-year RFS were not significantly different between the two groups. CONCLUSION: Regarding LRPPG, preserving the IPV did not help prevent DGE and resulted in no significant difference in the outcomes.

Impact of preoperative wait time on survival in patients with clinical stage II/III gastric cancer.

BACKGROUND: Preoperative wait time is affected by various factors, and a certain time is needed before surgery. There is a concern that cancer treatment delay can lead to poor survival. The present study aimed to evaluate the impact of preoperative wait time on survival in patients with clinical stage (cStage) II/III gastric cancer. METHODS: The study included patients with cStage II/III primary gastric cancer undergoing surgery between 2002 and 2012. Preoperative wait time was defined as the time from endoscopy for initial diagnosis to surgery. Patients were divided into the following three groups according to wait time: short wait group (≤ 30 days), intermediate wait group (> 30 and ≤ 60 days), and long wait group (> 60 and ≤ 90 days). Patient characteristics and survival were compared among the groups. RESULTS: This study included 467 male (67%) and 229 female (33%) patients, and the median patient age was 67 years. The numbers of cStage II and III patients were 332 (48%) and 364 (52%), respectively. The median wait time was 45 days. The body mass index was lower in the short wait group than in the other groups. A shorter wait time tended to be associated with a more advanced cStage. Although survival was significantly worse in the short wait group than in the long wait group, wait time was not identified as an independent prognostic factor in multivariate analysis. CONCLUSION: Preoperative wait time up to 90 days does not affect survival in patients with cStage II/III gastric cancer.

Iteroparity of stream resident masu salmon Oncorhynchus masou.

The degree of iteroparity in stream-resident forms of masu salmon Oncorhynchus masou was examined using mark-recapture studies in natural streams. In a partially migratory population, at least 10% of resident males survived after maturation and repeatedly matured for up to 5 years. In the landlocked amago salmon subspecies, the post-maturation survival rate was at least 7% and repeat maturation was observed for up to 3 years for both males and females.

Spatio-temporal dynamics of alternative male phenotypes in coho salmon populations in response to ocean environment.

1. The coexistence of alternative reproductive phenotypes will probably be shaped by spatial and temporal variability in the environment. However, the effects of such variability on coexistence and the scale at which it operates are seldom understood. 2. To quantify such effects, we examined spatial and temporal dynamics in the abundance and frequency of alternative phenotypes of male coho salmon, Oncorhynchus kisutch Walbaum, which mature as either large fighters (age-3 'hooknoses') or small sneakers (age-2 'jacks'). Using over 20 years of data on coded-wire tagged fish released from nine Oregon hatcheries, we tested for the effects of ocean environment independent of those due to freshwater rearing. 3. Annual fluctuations of the abundance of jack and hooknose males within populations were correlated strongly by brood year (cohort) but not by return year (breeding group). This occurred independently of significant effects of release practice (i.e. the number of fish released, body size at release and date of release), indicating that a synchronized fluctuation in mortality during the first year at sea was the predominant cause. As a result, the annual frequency of the alternative phenotypes at breeding varied considerably within populations. 4. Spatial patterns in the annual fluctuations of the two phenotypes were similar (i.e. synchronous among populations), except that jacks showed local spatial structure (decreased synchrony with distance) not evident among hooknoses. This suggests that oceanic processes affecting the two phenotypes operate at different spatial scales. Despite effects on salmon abundance, the ocean environment had little influence through its effects on salmon growth on the relative frequencies of the alternative phenotypes within and among populations. 5. The results provide insight into the evolutionary dynamics of alternative phenotypes, including an intragenerational time lag that increases annual variability in phenotype frequencies at breeding (return years) and the significance of local freshwater processes, rather than oceanic processes, on phenotype expression. Freshwater processes, such as juvenile growth, timing of migration and breeding competition, operating at evolutionary and intragenerational time-scales, are probably the predominant forces affecting phenotype frequency.