Gastric Cancer最新文献

Background

A postoperative pancreatic fistula (POPF) is a critical complication of radical gastrectomy for gastric cancer, mainly because surgeons occasionally misrecognize the pancreas and fat during lymphadenectomy. Therefore, this study aimed to develop an artificial intelligence (AI) system capable of identifying and highlighting the pancreas during robot-assisted gastrectomy.

Methods

A pancreas recognition algorithm was developed using HRNet, with 926 training images and 232 validation images extracted from 62 scenes of robot-assisted gastrectomy videos. During quantitative evaluation, the precision, recall, intersection over union (IoU), and Dice coefficients were calculated based on the surgeons’ ground truth and the AI-inferred image from 80 test images. During the qualitative evaluation, 10 surgeons answered two questions related to sensitivity and similarity for assessing clinical usefulness.

Results

The precision, recall, IoU, and Dice coefficients were 0.70, 0.59, 0.46, and 0.61, respectively. Regarding sensitivity, the average score for pancreas recognition by AI was 4.18 out of 5 points (1 = lowest recognition [less than 50%]; 5 = highest recognition [more than 90%]). Regarding similarity, only 54% of the AI-inferred images were correctly differentiated from the ground truth.

Conclusions

Our surgical AI system precisely highlighted the pancreas during robot-assisted gastrectomy at a level that was convincing to surgeons. This technology may prevent misrecognition of the pancreas by surgeons, thus leading to fewer POPFs.

Background

While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years).

Methods

We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson’s Test.

Results

The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: − 0.95; 95% confidence interval [CI] − 1.25 to − 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: − 1.23; 95% CI − 1.39 to − 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: − 1.82; 95% CI − 2.15 to − 1.56; P < 0.001 and AAPC: − 1.69, 95% CI − 1.79 to − 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: − 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: − 0.11, P = 0.13).

Conclusions

The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.

Background

Fluorescent lymphography (FL) using indocyanine green (ICG) allows for the visualization of all draining lymph nodes (LNs), thereby increasing LN retrieval. However, no studies have assessed the efficacy of FL in high body mass index (BMI) gastric cancer patients, even as LN yield decreases with increasing BMI in gastrectomy. This study aimed to investigate the influence of FL on LN retrieval in high BMI gastric cancer patients.

Methods

Gastric cancer patients who underwent laparoscopic or robotic gastrectomies from 2013 to 2021 were included. Patients were classified into two groups, with FL (FL group) or without FL (non-FL group). The effect of FL on LN retrieval was assessed by BMI. Inverse probability of treatment weighting (IPTW) was used to ensure comparability between groups.

Results

Retrieved LN number decreased as BMI increased regardless of FL application (P < 0.001). According to the IPTW analysis, the mean retrieved LN number was significantly higher in the FL group (48.4 ± 18.5) than in the non-FL group (39.8 ± 16.3, P < 0.001), irrespective of BMI. The FL group exhibited a significantly higher proportion of patients with 16 or more LNs (99.5%) than the non-FL group (98.1%, P < 0.001). The FL group also had a significantly higher proportion of patients with 30 or more LNs (86.6%) than the non-FL group (72.2%, P < 0.001). In both the normal and high-BMI patients, the FL group had a significantly larger percentage of patients with a higher nodal classification than the non-FL group.

Conclusion

FL resulted in more LN retrieval, even in high BMI patients. FL ensures accurate staging by maintaining the appropriate retrieved LN number in high BMI gastric cancer patients.

Background: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial.

Methods: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m², day 1), oxaliplatin (100 mg/m², day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria.

Results: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred.

Conclusions: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Introduction: Contour maps enable risk classification of GIST recurrence in individual patients within 10 postoperative years. Although contour maps have been referred to in Japanese guidelines, their usefulness and role in determining indications for adjuvant therapy is still unclear in Japanese patients. The aims of this study are to investigate the validity of contour maps in Japanese patients with GIST and explore the new strategy for adjuvant therapy.

Materials and methods: A total of 1426 Japanese GIST patients who were registered to the registry by the Kinki GIST Study Group between 2003 and 2012 were analyzed. Patients who had R0 surgery without perioperative therapy were included in this study. The accuracy of contour maps was validated.

Results: Overall, 994 patients have concluded this study. Using contour maps, we validated the patients. The 5-year recurrence-free survival rates of patients within the GIST classification groups of 0-10%, 10-20%, 20-40%, 40-60%, 60-80%, 80-90%, and 90-100% were 98.1%, 96.6%, 92.3%, 48.0%, 37.3%, 41.0% and 42.4%, respectively. We confirmed that this classification by contour maps was well reflected recurrence prediction. Further, in the high-risk group stratified by the modified National Institutes of Health consensus criteria (m-NIHC), the 10-year RFS rate was remarkably changed at a cutoff of 40% (0-40% group vs. 40-100% group: 88.7% vs. 50.3%, p < 0.001).

Conclusion: Contour maps are effective in predicting individual recurrence rates. And it may be useful for the decision of individual strategy for high-risk patients combined with m-NIHC.

Background: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea.

Methods: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed.

Results: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males.

Conclusions: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Helicobacter pylori (H. pylori, Hp) has been designated a class I carcinogen and is closely associated with severe gastric diseases. During colonization in the gastric mucosa, H. pylori develops immune escape by inducing host immune tolerance. The gastric epithelium acts as the first line of defense against H. pylori, with Toll-like receptors (TLRs) in gastric epithelial cells being sensitive to H. pylori components and subsequently activating the innate immune system. However, the mechanism of immune tolerance induced by H. pylori through the TLR signalling pathway has not been fully elucidated. In this research, we detected the expression of TLRs and inflammatory cytokines in GES-1 cells upon sustained exposure to H. pylori or H. pylori lysate from 1 to 30 generations and in Mongolian gerbils infected with H. pylori for 5 to 90 weeks. We found that the levels of TLR6 and inflammatory cytokines first increased and then dropped during the course of H. pylori treatment in vitro and in vivo. The restoration of TLR6 potentiated the expression of IL-1β and IL-8 in GES-1 cells, which recruited neutrophils and reduced the colonization of H. pylori in the gastric mucosa of gerbils. Mechanistically, we found that persistent infection with H. pylori reduces the sensitivity of TLR6 to bacterial components and regulates the expression of inflammatory cytokines in GES-1 cells through TLR6/JNK signaling. The TLR6 agonist obviously alleviated inflammation in vitro and in vivo. Promising results suggest that TLR6 may be a potential candidate immunotherapy drug for H. pylori infection.

Background: Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited.

Methods: GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur-gimeracil-oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed.

Results: A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups.

Conclusion: Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups.

Background: Mucosal gastric atrophy and intestinal metaplasia (IM) increase the risk for the development of gastric cancer (GC) as they represent a field for development of dysplasia and intestinal-type gastric adenocarcinoma.

Methods: We have investigated the expression of two dysplasia markers, CEACAM5 and TROP2, in human antral IM and gastric tumors to assess their potential as molecular markers.

Results: In the normal antral mucosa, weak CEACAM5 and TROP2 expression was only observed in the foveolar epithelium, while inflamed antrum exhibited increased expression of both markers. Complete IM exhibited weak CEACAM5 expression at the apical surface, but no basolateral TROP2 expression. On the other hand, incomplete IM demonstrated high levels of both CEACAM5 and TROP2 expression. Notably, incomplete IM with dysplastic morphology (dysplastic incomplete IM) exhibited higher levels of CEACAM5 and TROP2 expression compared to incomplete IM without dysplastic features (simple incomplete IM). In addition, dysplastic incomplete IM showed diminished SOX2 and elevated CDX2 expression compared to simple incomplete IM. CEACAM5 and TROP2 positivity in incomplete IM was similar to that of gastric adenomas and GC. Significant association was found between CEACAM5 and TROP2 positivity and histology of GC.

Conclusions: These findings support the concept that incomplete IM is more likely associated with GC development. Overall, our study provides evidence of the heterogeneity of gastric IM and the distinct expression profiles of CEACAM5 and TROP2 in dysplastic incomplete IM. Our findings support the potential use of CEACAM5 and TROP2 as molecular markers for identifying individuals with a higher risk of GC development in the context of incomplete IM.

Background: Gastric cancer (GC), the fourth leading cause of cancer-related death worldwide, with most deaths caused by advanced and metastatic disease, has limited curative options. Here, we revealed the importance of proprotein convertases (PCs) in the malignant and metastatic potential of GC cells through the regulation of the YAP/TAZ/TEAD pathway and epithelial-to-mesenchymal transition (EMT) in cancer stem cells (CSC).

Methods: The general PCs inhibitor, decanoyl-RVKR-chloromethyl-ketone (CMK), was used to repress PCs activity in CSCs of various GC cell lines. Their tumorigenic properties, drug resistance, YAP/TAZ/TEAD pathway activity, and invasive properties were then investigated in vitro, and their metastatic properties were explored in a mouse xenograft model. The prognostic value of PCs in GC patients was also explored in molecular databases of GC.

Results: Inhibition of PCs activity in CSCs in all GC cell lines reduced tumorsphere formation and growth, drug efflux, EMT phenotype, and invasive properties that are associated with repressed YAP/TAZ/TEAD pathway activity in vitro. In vivo, PCs' inhibition in GC cells reduced their metastatic spread. Molecular analysis of tumors from GC patients has highlighted the prognostic value of PCs.

Conclusions: PCs are overexpressed in GC and associated with poor prognosis. PCs are involved in the malignant and metastatic potential of CSCs via the regulation of EMT, the YAP/TAZ/TEAD oncogenic pathway, and their stemness and invasive properties. Their repression represents a new strategy to target CSCs and impair metastatic spreading in GC.