Pub Date : 2024-11-01Epub Date: 2024-07-04DOI: 10.1007/s10120-024-01531-4
Kuan-Fu Liao, Shih-Wei Lai
{"title":"Comment on \"Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study\".","authors":"Kuan-Fu Liao, Shih-Wei Lai","doi":"10.1007/s10120-024-01531-4","DOIUrl":"10.1007/s10120-024-01531-4","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1007/s10120-024-01559-6
{"title":"Acknowledgment to Reviewers.","authors":"","doi":"10.1007/s10120-024-01559-6","DOIUrl":"https://doi.org/10.1007/s10120-024-01559-6","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.
Methods: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).
Results: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.
Conclusions: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.
{"title":"Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).","authors":"Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro","doi":"10.1007/s10120-024-01555-w","DOIUrl":"https://doi.org/10.1007/s10120-024-01555-w","url":null,"abstract":"<p><strong>Background: </strong>Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.</p><p><strong>Methods: </strong>Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).</p><p><strong>Results: </strong>Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.</p><p><strong>Conclusions: </strong>T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.</p><p><strong>Clinical trial registration: </strong>UMIN000049032.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1007/s10120-024-01558-7
Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren
Background: Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour.
Methods: This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers.
Results: Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location.
Conclusion: Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.
背景:化疗的晚期效应可能会影响癌症幸存者的死亡率。本研究旨在明确胃腺癌新辅助化疗是否会影响该肿瘤治愈者的长期生存:这是一项基于人口的全国性队列研究,研究对象包括2006年至2015年间在瑞典因胃腺癌接受胃切除术且术后存活≥5年的所有患者。队列随访至死亡或研究期结束(2020 年 12 月 31 日)。采用多变量考克斯比例危险度回归法得出危险度比 (HR),并得出 95% 的置信区间 (CI)。HR已根据年龄、性别、合并症、教育程度、日历年、肿瘤亚位置、院内并发症和脾切除术进行了调整。数据来自医疗记录和全国范围内的登记:结果:在 613 名胃癌幸存者中,新辅助化疗(269 名患者,43.9%)与粗死亡率的降低有关(HR 0.66,95% CI 0.46-0.96)。然而,在对所有混杂因素进行调整后(HR 0.83,95% CI 0.56-1.23),以及仅对年龄和合并症进行调整后(HR 0.82,95% CI 0.56-1.20),这种关联性减弱,在统计学上变得不显著。分层分析未发现新辅助化疗与年龄、性别、合并症、日历年和肿瘤亚定位等类别的长期死亡率有任何统计学意义:结论:新辅助化疗不会降低胃腺癌幸存者的长期生存率。接受新辅助化疗的患者是经过筛选的群体,他们的特点是年龄较小、严重合并症较少,因此长期生存的机会更大。
{"title":"Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.","authors":"Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren","doi":"10.1007/s10120-024-01558-7","DOIUrl":"https://doi.org/10.1007/s10120-024-01558-7","url":null,"abstract":"<p><strong>Background: </strong>Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour.</p><p><strong>Methods: </strong>This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers.</p><p><strong>Results: </strong>Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location.</p><p><strong>Conclusion: </strong>Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1007/s10120-024-01556-9
Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen
Background: Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).
Methods: Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.
Results: ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).
Conclusion: ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.
{"title":"Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.","authors":"Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen","doi":"10.1007/s10120-024-01556-9","DOIUrl":"https://doi.org/10.1007/s10120-024-01556-9","url":null,"abstract":"<p><strong>Background: </strong>Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).</p><p><strong>Methods: </strong>Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.</p><p><strong>Results: </strong>ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).</p><p><strong>Conclusion: </strong>ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1007/s10120-024-01557-8
Bokyung Ahn, Deokhoon Kim, Mi-Ju Kim, Seo-Rin Jeong, In Hye Song, Joo Young Kim, Soon Auck Hong, Sun-Young Jun, HyungJun Cho, Young Soo Park, Freddy E Escorcia, Joon-Yong Chung, Seung-Mo Hong
Background: Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown.
Methods: The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers.
Results: Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS.
Conclusion: The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and more effective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.
{"title":"Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions.","authors":"Bokyung Ahn, Deokhoon Kim, Mi-Ju Kim, Seo-Rin Jeong, In Hye Song, Joo Young Kim, Soon Auck Hong, Sun-Young Jun, HyungJun Cho, Young Soo Park, Freddy E Escorcia, Joon-Yong Chung, Seung-Mo Hong","doi":"10.1007/s10120-024-01557-8","DOIUrl":"https://doi.org/10.1007/s10120-024-01557-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown.</p><p><strong>Methods: </strong>The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers.</p><p><strong>Results: </strong>Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS.</p><p><strong>Conclusion: </strong>The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and more effective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Gastric cancer is a common malignancy with a high incidence in East Asia. Gastric resection ranges from endoscopic resection to open total gastrectomy. However, nationwide data are lacking.
Methods: This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the types of resection performed for malignant gastric tumors between 2014 and 2021, patients' age and sex distributions, and regional disparities were investigated.
Results: The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while that of total gastrectomies decreased from 17 to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection were aged ≥ 65 years. The annual incidence of gastric resection per million population was highest in Tottori (n = 1236) and lowest in Okinawa (n = 251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).
Conclusions: Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than open total gastrectomy. However, regional disparities remain in resection type. Standardization of treatment and a more even distribution of specialists are needed.
{"title":"Clinical epidemiology of the endoscopic, laparoscopic, and surgical resection of malignant gastric tumors in Japan, 2014-2021: a retrospective study using open data from a national claims database.","authors":"Akahito Sako, Tomoyuki Yada, Keiichi Fujiya, Ryo Nakashima, Kensuke Yoshimura, Hidekatsu Yanai, Naomi Uemura","doi":"10.1007/s10120-024-01553-y","DOIUrl":"https://doi.org/10.1007/s10120-024-01553-y","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is a common malignancy with a high incidence in East Asia. Gastric resection ranges from endoscopic resection to open total gastrectomy. However, nationwide data are lacking.</p><p><strong>Methods: </strong>This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the types of resection performed for malignant gastric tumors between 2014 and 2021, patients' age and sex distributions, and regional disparities were investigated.</p><p><strong>Results: </strong>The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while that of total gastrectomies decreased from 17 to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection were aged ≥ 65 years. The annual incidence of gastric resection per million population was highest in Tottori (n = 1236) and lowest in Okinawa (n = 251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).</p><p><strong>Conclusions: </strong>Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than open total gastrectomy. However, regional disparities remain in resection type. Standardization of treatment and a more even distribution of specialists are needed.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer.
Methods
We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo.
Results
In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index.
Conclusions
We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer.
{"title":"Lipolysis-stimulated lipoprotein receptor promote lipid uptake and fatty acid oxidation in gastric cancer","authors":"Kota Kawabata, Tsuyoshi Takahashi, Koji Tanaka, Yukinori Kurokawa, Kazuyoshi Yamamoto, Takuro Saito, Kota Momose, Kotaro Yamashita, Tomoki Makino, Takashi Yokouchi, Kunihiko Kawai, Satoshi Serada, Minoru Fujimoto, Kiyokazu Nakajima, Tetsuji Naka, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.1007/s10120-024-01552-z","DOIUrl":"https://doi.org/10.1007/s10120-024-01552-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1007/s10120-024-01554-x
Lingyu Xu, Siqi Jiang, Tianyang Li, Yan Xu
The article by Shin et al. provides valuable insights into the correlation between the gastric mucosa-associated gastric microbiome (MAM) and metachronous recurrence. However, the use of the Cox proportional hazards model in their analysis presents several limitations. The study may result in mixed censoring outcomes, and the assumption of constant hazard ratios over time may not hold. Considering these limitations, future research should adopt alternative approaches, such as the accelerated failure time (AFT) model, to provide a more comprehensive understanding of the relationship between gastric MAM and metachronous recurrence.
Shin 等人的文章就胃黏膜相关胃微生物组(MAM)与远期复发之间的相关性提供了有价值的见解。然而,他们在分析中使用的 Cox 比例危险模型存在一些局限性。该研究可能会导致混合普查结果,而且随着时间推移危险比恒定的假设可能不成立。考虑到这些局限性,未来的研究应采用其他方法,如加速衰竭时间(AFT)模型,以更全面地了解胃癌 MAM 与远期复发之间的关系。
{"title":"Limitations of the cox proportional hazards model and alternative approaches in metachronous recurrence research","authors":"Lingyu Xu, Siqi Jiang, Tianyang Li, Yan Xu","doi":"10.1007/s10120-024-01554-x","DOIUrl":"https://doi.org/10.1007/s10120-024-01554-x","url":null,"abstract":"<p>The article by Shin et al. provides valuable insights into the correlation between the gastric mucosa-associated gastric microbiome (MAM) and metachronous recurrence. However, the use of the Cox proportional hazards model in their analysis presents several limitations. The study may result in mixed censoring outcomes, and the assumption of constant hazard ratios over time may not hold. Considering these limitations, future research should adopt alternative approaches, such as the accelerated failure time (AFT) model, to provide a more comprehensive understanding of the relationship between gastric MAM and metachronous recurrence.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurate prediction of peritoneal recurrence for gastric cancer (GC) is crucial in clinic. The collagen alterations in tumor microenvironment affect the migration and treatment response of cancer cells. Herein, we proposed multitask machine learning-based tumor-associated collagen signatures (TACS), which are composed of quantitative collagen features derived from multiphoton imaging, to simultaneously predict peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS).
Methods
Among 713 consecutive patients, with 275 in training cohort, 222 patients in internal validation cohort, and 216 patients in external validation cohort, we developed and validated a multitask machine learning model for simultaneously predicting peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). The accuracy of the model for prediction of peritoneal recurrence and prognosis as well as its association with adjuvant chemotherapy were evaluated.
Results
The TACSPR and TACSDFS were independently associated with peritoneal recurrence and disease-free survival in three cohorts, respectively (all P < 0.001). The TACSPR demonstrated a favorable performance for peritoneal recurrence in all three cohorts. In addition, the TACSDFS also showed a satisfactory accuracy for disease-free survival among included patients. For stage II and III diseases, adjuvant chemotherapy improved the survival of patients with low TACSPR and low TACSDFS, or high TACSPR and low TACSDFS, or low TACSPR and high TACSDFS, but had no impact on patients with high TACSPR and high TACSDFS.
Conclusions
The multitask machine learning model allows accurate prediction of peritoneal recurrence and survival for GC and could distinguish patients who might benefit from adjuvant chemotherapy.
背景准确预测胃癌(GC)腹膜复发在临床上至关重要。肿瘤微环境中的胶原蛋白改变会影响癌细胞的迁移和治疗反应。在此,我们提出了基于多任务机器学习的肿瘤相关胶原特征(TACS),该特征由多光子成像得到的定量胶原特征组成,可同时预测腹膜复发(TACSPR)和无病生存(TACSDFS)。方法在713例连续患者(其中275例为训练队列,222例为内部验证队列,216例为外部验证队列)中,我们开发并验证了同时预测腹膜复发(TACSPR)和无病生存(TACSDFS)的多任务机器学习模型。结果在三个队列中,TACSPR 和 TACSDFS 分别与腹膜复发和无病生存率独立相关(均为 P <0.001)。在所有三个队列中,TACSPR 在腹膜复发方面表现良好。此外,TACSDFS 对纳入患者的无病生存率也显示出令人满意的准确性。对于II期和III期疾病,辅助化疗提高了低TACSPR和低TACSDFS、或高TACSPR和低TACSDFS、或低TACSPR和高TACSDFS患者的生存率,但对高TACSPR和高TACSDFS患者没有影响。
{"title":"Multitask machine learning-based tumor-associated collagen signatures predict peritoneal recurrence and disease-free survival in gastric cancer","authors":"Meiting Fu, Yuyu Lin, Junyao Yang, Jiaxin Cheng, Liyan Lin, Guangxing Wang, Chenyan Long, Shuoyu Xu, Jianping Lu, Guoxin Li, Jun Yan, Gang Chen, Shuangmu Zhuo, Dexin Chen","doi":"10.1007/s10120-024-01551-0","DOIUrl":"https://doi.org/10.1007/s10120-024-01551-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Accurate prediction of peritoneal recurrence for gastric cancer (GC) is crucial in clinic. The collagen alterations in tumor microenvironment affect the migration and treatment response of cancer cells. Herein, we proposed multitask machine learning-based tumor-associated collagen signatures (TACS), which are composed of quantitative collagen features derived from multiphoton imaging, to simultaneously predict peritoneal recurrence (TACS<sub>PR</sub>) and disease-free survival (TACS<sub>DFS</sub>).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Among 713 consecutive patients, with 275 in training cohort, 222 patients in internal validation cohort, and 216 patients in external validation cohort, we developed and validated a multitask machine learning model for simultaneously predicting peritoneal recurrence (TACS<sub>PR</sub>) and disease-free survival (TACS<sub>DFS</sub>). The accuracy of the model for prediction of peritoneal recurrence and prognosis as well as its association with adjuvant chemotherapy were evaluated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The TACS<sub>PR</sub> and TACS<sub>DFS</sub> were independently associated with peritoneal recurrence and disease-free survival in three cohorts, respectively (all <i>P</i> < 0.001). The TACS<sub>PR</sub> demonstrated a favorable performance for peritoneal recurrence in all three cohorts. In addition, the TACS<sub>DFS</sub> also showed a satisfactory accuracy for disease-free survival among included patients. For stage II and III diseases, adjuvant chemotherapy improved the survival of patients with low TACS<sub>PR</sub> and low TACS<sub>DFS</sub>, or high TACS<sub>PR</sub> and low TACS<sub>DFS</sub>, or low TACS<sub>PR</sub> and high TACS<sub>DFS</sub>, but had no impact on patients with high TACS<sub>PR</sub> and high TACS<sub>DFS</sub>.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The multitask machine learning model allows accurate prediction of peritoneal recurrence and survival for GC and could distinguish patients who might benefit from adjuvant chemotherapy.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}