Journal of Gastric Cancer最新文献

Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context.

Materials and methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10³/mm³)/lymphocyte count (10³/mm³). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance.

Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014).

Conclusions: The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.

Materials and methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.

Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60). In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.

Conclusions: CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM.

Materials and methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed.

Results: The median patient age was 56 years (range, 34-66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology. The median tumor size was 5.8 cm (range, 2.0 cm-15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%). Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM. C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis.

Conclusions: Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Purpose: Despite extensive research on gastric cancer (GC), efforts to consolidate the numerous associations between possible factors and GC risk remain lacking. This systematic review aimed to provide an overview of potential GC-associated pairs.

Materials and methods: We systematically searched PubMed, Embase, and Cochrane databases, from their inception to April 23, 2022, for eligible systematic reviews and meta-analyses to investigate the association between any possible factors and GC risk. After the inclusion of 75 systematic reviews and meta-analyses, 117 association pairs were examined. We reanalyzed the included meta-analyses and produced effect estimates using uniform analytical models. The certainty of the evidence for each association pair was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria.

Results: Iatrogenic factors, including antibacterial drugs, were associated with an increased risk of GC. Epstein-Barr virus and Helicobacter pylori infections were also associated with an increased risk of GC, while human T-lymphotropic virus type 1 (HTLV-1) infections were associated with a reduced risk. Dietary habit was a major factor influencing moderate to high GRADE associations. Positive associations were observed for heavy alcohol consumption (relative risk [RR], 1.13; 95% confidence interval [CI], 1.06-1.12), refined grain consumption (RR, 1.36; 95% CI, 1.21-1.53), and habitual salt intake (RR, 1.41; 95% CI, 1.04-1.91).

Conclusions: The associations between GC risk and dietary and nutritional factors were considerably heterogeneous, whereas other factors, such as lifestyle and iatrogenic and environmental exposures, were consistent across regions. Therefore, dietary interventions for GC prevention should be tailored specific to regions.

Trial registration: PROSPERO Identifier: CRD42020209817.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer.

Materials and methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery.

Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both). Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064).

Conclusions: Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Purpose: This study aimed to evaluate the outcomes and current status of reduced-port laparoscopic distal gastrectomy (RLDG) compared with multiport laparoscopic distal gastrectomy (MLDG) based on a 2019 nationwide survey of surgical gastric cancer treatments by the Korean Gastric Cancer Association (KGCA).

Materials and methods: The study was conducted retrospectively from March to December 2020 using data from the 2019 KGCA nationwide survey database. To compare RLDG and MLDG based on age, sex, body mass index, American Society of Anesthesiologists score, histological type, tumor invasion, and lymph node metastasis, propensity score matching was performed.

Results: Of the 14,076 registered patients with gastric cancer, the five-port approach was the most favored for multiport gastrectomy, accounting for 6,396 (70.9%) cases, followed by the four-port approach, with 1,462 (16.2%) cases. The single-port approach was used in 303 (3.4%) cases, the two-port approach in 95 (1.1%) cases, and the three-port approach in 731 (8.1%) cases. RLDG was performed in 805 patients (6.4%), MLDG was conducted in 4,831 patients (34.3%), and 804 patients were 1:1 matched in each group. The average operation time was shorter in the RLDG (168.2±49.1 min vs. 179.5±61.5 min, P<0.001). No significant difference was found in blood loss (84.8±115.9 cc vs. 75.5±119.6 cc, P=0.152), overall complication rates (11.3% vs. 13.1%, P=0.254), or complications ≥ to grade IIIa (3.2% vs. 4.4%, P=0.240).

Conclusions: This study revealed that RLDG is a safe and effective surgical option for gastric cancer with the potential to offer shorter operation times without increasing the risk of complications.

This corrects the article on p. 356 in vol. 24, PMID: 39375052.

Purpose: Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex.

Materials and methods: We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service-Health Screening database, using data from 2009-2019. Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities.

Results: The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500-999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.98). Especially in males with WC <90 cm and BMI <23 kg/m², a lower risk of GC was observed in the group with METs/week of 1-499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67-0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females.

Conclusions: Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023.

Materials and methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys.

Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023. Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014. The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023. However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively.

Conclusions: The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Gastric cancer (GC) is a highly heterogeneous disease that varies in both histological presentation and genetic characteristics. Recent advances in the treatment of metastatic and unresectable GC have made several biomarker tests essential for patient management. Predictive biomarkers such as human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), mismatch-repair (MMR) proteins, claudin 18.2, and fibroblast growth factor receptor 2b (FGFR2b) are commonly evaluated using immunohistochemistry. However, the expression levels of these biomarkers may vary across different tumor areas, and the accuracy of biomarker diagnosis can be affected by sample quantity, sample location, and collection method. Therefore, tumor heterogeneity presents substantial challenges for accurate biomarker-based diagnosis and prediction of therapeutic responses. Tumor heterogeneity can be categorized into spatial heterogeneity, which refers to variations within the primary tumor (intra-tumoral) or between primary and metastatic sites, and temporal heterogeneity, which encompasses changes over time. This review addresses the tumor heterogeneity in predictive biomarker expression in GC, focusing on HER2, PD-L1, MMR, the Epstein-Barr virus, claudin 18.2, and FGFR2b.