Journal of Gastric Cancer最新文献

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy.

Materials and methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level.

Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020).

Conclusions: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Trial registration: ClinicalTrials.gov Identifier: NCT02289547.

Purpose: Although chylous ascites is a frequent complication of radical gastrectomy for gastric cancer, proper diagnostic criteria and optimal treatment strategies have not been established. This study aimed to identify the clinical features of chylous ascites and evaluate the treatment outcomes.

Materials and methods: We retrospectively analyzed the data of patients who underwent radical gastrectomy between 2013 and 2019. Diagnosis was made when milky fluid or elevated triglyceride levels (≥100 mg/dL) appeared in the drains without a preceding infection. The clinical features, risk factors, and treatment outcomes were assessed according to the initial treatment modalities for fasting and non-fasting groups.

Results: Among the 7,388 patients who underwent radical gastrectomy for gastric cancer, 156 (2.1%) experienced chylous ascites. The median length of hospital stay was longer in patients with chylous ascites than in those without (median [interquartile range]: 8.0 [6.0-12.0] vs. 6.0 [5.0-8.0], P<0.001). Low body mass index (adjusted odds ratio [aOR]=0.9; P<0.001), advanced gastric cancer (aOR=1.51, P=0.024), open surgery (reference: laparoscopic surgery; aOR=1.87, P=0.003), and extent of surgical resection (reference: subtotal gastrectomy, total gastrectomy, aOR=1.5, P=0.029; proximal gastrectomy, aOR=2.93, P=0.002) were associated with the occurrence of chylous ascites. The fasting group (n=12) was hospitalized for a longer period than the non-fasting group (n=144) (15.0 [12.5-19.5] vs. 8.0 [6.0-10.0], P<0.001). There was no difference in grade III complication rate (16.7% vs. 4.2%, P=0.117) or readmission rate (16.7% vs. 11.1%, P=0.632) between the groups.

Conclusions: A fat-controlled diet and medication without fasting provided adequate initial treatment for chylous ascites after radical gastrectomy for gastric cancer.

Purpose: In this study, polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for mismatch repair (MMR) protein expression in patients with gastric cancer (GC).

Materials and methods: In 5,676 GC cases, PCR-based MSI testing using five microsatellites (BAT-26, BAT-25, D5S346, D2S123, and D17S250) and IHC for MLH1 were performed. Re-evaluation of MSI testing/MLH1 IHC and additional IHC for MSH2, MSH6, and PMS2 were performed in discordant/indeterminate cases.

Results: Of the 5,676 cases, microsatellite stable (MSS)/MSI-low and intact MLH1 were observed in 5,082 cases (89.5%), whereas MSI-high (MSI-H) and loss of MLH1 expression were observed in 502 cases (8.8%). We re-evaluated the remaining 92 cases (1.6%) with a discordant/indeterminate status. Re-evaluation showed 1) 37 concordant cases (0.7%) (18 and 19 cases of MSI-H/MMR-deficient (dMMR) and MSS/MMR-proficient (pMMR), respectively), 2) 6 discordant cases (0.1%) (3 cases each of MSI-H/pMMR and MSS/dMMR), 3) 14 MSI indeterminate cases (0.2%) (1 case of dMMR and 13 cases of pMMR), and 4) 35 IHC indeterminate cases (0.6%) (22 and 13 cases of MSI-H and MSS, respectively). Finally, MSI-H or dMMR was observed in 549 cases (9.7%), of which 47 (0.8%) were additionally confirmed as MSI-H or dMMR by re-evaluation. Sensitivity was 99.3% for MSI testing and 95.4% for MMR IHC.

Conclusions: Considering the low incidence of MSI-H or dMMR, discordant/indeterminate results were occasionally identified in GCs, in which case complementary testing is required. These findings could help improve the accuracy of MSI/MMR testing in daily practice.

Purpose: This study aimed to examine the effects of 4 main types of gastrectomy for proximal gastric cancer on postoperative symptoms, living status, and quality of life (QOL) using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45).

Materials and methods: We surveyed 1,685 patients with upper one-third gastric cancer who underwent total gastrectomy (TG; n=1,020), proximal gastrectomy (PG; n=518), TG with jejunal pouch reconstruction (TGJP; n=93), or small remnant distal gastrectomy (SRDG; n=54). The 19 main outcome measures (MOMs) of the PGSAS-45 were compared using the analysis of means (ANOM), and the general QOL score was calculated for each gastrectomy type.

Results: Patients who underwent TG experienced the lowest postoperative QOL. ANOM showed that 10 MOMs were worse in patients with TG. Four MOMs improved in patients with PG, while 1 worsened. One MOM was improved in patients with TGJP versus 8 MOMs in patients with SRDG. The general QOL scores were as follows: SRDG (+39 points), TGJP (+6 points), PG (+3 points), and TG (-1 point).

Conclusions: The TG group experienced the greatest decline in postoperative QOL. SRDG and PG, which preserve part of the stomach without compromising curability, and TGJP, which is used when TG is required, enhance the postoperative QOL of patients with proximal gastric cancer. When selecting the optimal gastrectomy method, it is essential to understand the characteristics of each and actively incorporate guidance to improve postoperative QOL.

Background: There are no clear guidelines to determine whether to perform D1 or D1+ lymph node dissection in early gastric cancer (EGC). This study aimed to develop a nomogram for estimating the risk of extraperigastric lymph node metastasis (LNM).

Materials and methods: Between 2009 and 2019, a total of 4,482 patients with pathologically confirmed T1 disease at 6 affiliated hospitals were included in this study. The basic clinicopathological characteristics of the positive and negative extraperigastric LNM groups were compared. The possible risk factors were evaluated using univariate and multivariate analyses. Based on these results, a risk prediction model was developed. A nomogram predicting extraperigastric LNM was used for internal validation.

Results: Multivariate analyses showed that tumor size (cut-off value 3.0 cm, odds ratio [OR]=1.886, P=0.030), tumor depth (OR=1.853 for tumors with sm2 and sm3 invasion, P=0.010), cross-sectional location (OR=0.490 for tumors located on the greater curvature, P=0.0303), differentiation (OR=0.584 for differentiated tumors, P=0.0070), and lymphovascular invasion (OR=11.125, P<0.001) are possible risk factors for extraperigastric LNM. An equation for estimating the risk of extraperigastric LNM was derived from these risk factors. The equation was internally validated by comparing the actual metastatic rate with the predicted rate, which showed good agreement.

Conclusions: A nomogram for estimating the risk of extraperigastric LNM in EGC was successfully developed. Although there are some limitations to applying this model because it was developed based on pathological data, it can be optimally adapted for patients who require curative gastrectomy after endoscopic submucosal dissection.

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline.

Materials and methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values.

Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05).

Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

Trial registration: ClinicalTrials.gov Identifier: NCT01170663.

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC.

Materials and methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq).

Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics.

Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Purpose: This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC).

Materials and methods: Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed.

Results: The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group.

Conclusions: Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted.

This corrects the article on p. 3 in vol. 23, PMID: 36750993.