Roles and application of exosomes in the development,diagnosis and treatment of gastric cancer

As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

The 2023 update of the Chinese Society of Clinical Oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision medicine.These updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer patients.Key revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric cancer.For advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients.Additionally,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer.The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

Treatment of early gastric cancer in the Western World

The incidence rate of gastric cancer is much higher in Asia than in the Western industrial nations.According to the different screening programs in Japan and Korea about fifty percent of treated patients had an early tumor stage.In contrast,European and American patients with gastric cancer had an advanced tumor stage.Therefore,the experience for the various therapeutic options for gastric cancer may be different between these regions.In this review we tried to point out the treatment modalities in Western industrial countries for early gastric cancer.

Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer

5-aminolevulinic acid(ALA) is a naturally occurring amino acid that is a protoporphyrin IX(Pp IX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, Pp IX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to Pp IX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis(PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy(PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and nearinfrared rays as light sources.

Clinical implications of interleukins-31, 32, and 33 in gastric cancer

BACKGROUND Gastric cancer(GC) is one of the most common malignancies in China with a high morbidity and mortality.AIM To determine whether interleukin(IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients.METHODS Tissue array(n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA.RESULTS We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues(P < 0.05). IL-33 in peripheral blood of GC patients was significantly lower than that of healthy individuals(1.50 ± 1.11 vs 9.61 ± 8.00 ng/m L, P <0.05). Decreased IL-31, IL-32, and IL-33 in GC were observed in younger patients(< 60 years), and IL-32 and IL-33 were lower in female patients(P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people(P < 0.05).CONCLUSION Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.

结直肠癌的早期诊断策略和治疗进展

通过筛查和早期发现,可以降低结直肠癌(CRC)的发病率,有效切除肿瘤病变可以降低CRC的病死率。虽然对CRC的危险因素、发病机制和前体病变的了解已经取得进展,但最近年轻人群CRC发病率升高,原因尚不清楚。在过去十年中,出现了多种侵入性、半侵入性和非侵入性筛查方式。目前对结肠镜检查质量的重视提高了筛查的有效性,人工智能等影像新技术在肿瘤检测中的作用正在迅速显现。而且,CRC有效干预措施,如保肛治疗新术式、靶向治疗及免疫治疗领域的新进展,被证明可以提高CRC患者的生存率。该文旨在总结目前国内外CRC筛查方式和指南的证据,并综述CRC治疗领域的进展。

胃癌外科综合治疗的若干进展与展望

胃癌是国内、外常见恶性肿瘤,手术仍是治疗胃癌的主要方法。一系列临床研究改变了传统胃癌手术理念,避免盲目扩大手术切除范围。腹腔镜手术治疗早期和局部进展期胃癌的疗效并不劣于开腹手术。胃癌微创手术发展的关键是把握合理的手术指征,建立手术技术培训系统,以及优化成本与效益。理性认识胃癌扩大术脏器切除与保留脏器功能的关系。注重局部进展期胃癌围术期治疗的全程管理。并提倡晚期胃癌的术前转化治疗。对广泛转移晚期胃癌的姑息性切除术应慎之又慎,建议综合治疗,旨在延长病人生命。

The Chinese Society of Clinical Oncology(CSCO):clinical guidelines for the diagnosis and treatment of gastric cancer

China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.

The Chinese Society of Clinical Oncology(CSCO):Clinical guidelines for the diagnosis and treatment of gastric cancer,2021

There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.

Artificial intelligence in theranostics of gastric cancer, a review

Gastric cancer (GC) is one of the commonestcancers with high morbidity and mortality in the world.How to realize precise diagnosis and therapy of GC ownsgreat clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to earlydiagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in earlyscreening, diagnosis, therapy and prognosis of stomachcarcinoma. Especially AI combined with breath screeningearly GC system improved 97.4 % of early GC diagnosisratio, AI model on stomach cancer diagnosis system of salivabiomarkers obtained an overall accuracy of 97.18 %, speci-ficity of 97.44 %, and sensitivity of 96.88 %. We also discussconcept, issues, approaches and challenges of AI applied instomach cancer. This review provides a comprehensive viewand roadmap for readers working in this field, with the aimof pushing application of AI in theranostics of stomachcancer to increase the early discovery ratio and curativeratio of GC patients.

胃癌穿孔的诊断和治疗

目的通过２４例胃癌穿孔病例临床资料的分析，对胃癌穿孔的诊断和治疗进行探讨。方法我院普外科１９９０年２月～１９９８年５月收治的胃癌穿孔病例２４例，男２０例，女４例，年龄５２～８４岁；术前诊断１４例，术中及术后诊断１０例。结果６例行单纯穿孔修补加活检术，１８例行胃癌根治术或全胃切除术；大体类型多为溃疡型（２２／２４例，８７５％）；病理多为低分化或未分化癌（１８／２２例，８１８％）；穿孔修补平均生存时间６月，胃癌根治或姑息切除平均生存时间１７月。结论胃癌穿孔病例存在着一定的临床特点，如患者年龄偏大、一般情况差、溃疡及穿孔直径大等，处理上应积极手术治疗，尽可能行根治或姑息手术切除病灶。

术前小探头超声内镜检查在早期胃癌治疗方式选择中的作用

目的评价小探头超声内镜(EUS)在早期胃癌(EGC)治疗方式选择中的作用。方法回顾性分析2011年1月-2013年12月北京大学肿瘤医院151例单发EGC临床病理资料。分析EUS判断EGC浸润深度的准确率及影响因素,评价基于EUS选择EGC治疗方法的策略。结果 EUS对EGC浸润深度判断的准确率为74.8%。多因素分析结果显示,肿瘤直径>2 cm、内镜下溃疡形成及病灶位于胃中上2/3是导致分期错误的危险因素(P<0.05)。75.3%(107/142)的EGC病例通过基于EUS评估获得了适合的治疗。结论小探头EUS在EGC浸润深度评估及治疗方式选择中具有良好实用性,当病灶直径大于2 cm、合并溃疡形成或位于胃中上部时,应当谨慎对待EUS结果。

胃癌的分子机制及靶向诊断研究进展

胃癌的发生发展涉及多个分子信号通路和许多细胞因子,其中比较重要的包括PI3K/AKT、MAPK通路,HER、VEGF/VEGFR、MET等生长因子及受体家族,COX-2、NF-κB、STAT、白介素家族等炎症相关因子,他们参与了胃癌细胞凋亡抑制、增殖促进、周期调控以及胃癌侵袭迁移、血管生成等过程。这些因子在胃癌中特异性表达,可以作为肿瘤标记物用于胃癌的靶向治疗,相应药物多已进入临床试验阶段。在上述理论基础上,胃癌靶向诊断也有了新的进展,闪烁扫描法、内镜等手段逐渐趋于成熟,但特异性探针的研究多处于临床前期阶段,仍有待进一步的发展。

早期胃癌手术率的演变及经验

目的总结上海瑞金医院7年间早期胃癌手术率的演变。方法统计2001年～2007年间外科胃癌切除手术例数、经切除标本病理学证实的早期胃癌数以及早期胃癌占胃癌总数的比例；按国际标准对确诊的早期胃癌进行形态学分类。结果7年间共行胃癌切除术2129例，经手术确认的早期胃癌340例。2001年～2004年间早期胃癌手术率为12．3％；2005年～2007年建立了多科联合的胃肠肿瘤学科群，早期胃癌手术率平均为19，6％，最高年手术率达到21，8％。检出的早期胃癌中以0-ⅡIc型最为多见，占67．1％；其次为0-Ⅲ型，占19．1％。结论早期胃癌的检出是一项经验积累的工作，多科协作是提高早期胃癌手术率的重要方法，我国应当努力开展无症状早期胃癌患者的筛选及诊断工作。

10年间早期胃癌手术率演变及经验

目的总结上海交通大学医学院附属瑞金医院10年间早期胃癌手术率演变。方法统计2001年1月～2010年12月间瑞金医院经外科手术治疗的胃癌患者例数,分析其中病理证实的早期胃癌数及其占胃癌总数的比例;按国际标准对确诊的早期胃癌进行形态分型。结果 10年间共行胃癌切除术4 197例,经手术确认早期胃癌727例。2001年～2004年间早期胃癌手术率为12.3%;在建立了多学科联合的胃肠肿瘤学科群后,2005年～2010年的早期胃癌手术率上升至19.0%,年手术率最高达20.7%,检出的早期胃癌中以凹陷型病灶多见,其中0-Ⅱc型327例(54.8%),0-Ⅲ型92例(15.4%),复合型63例(10.6%)。结论早期胃癌的检出有赖于多学科协作,我国早期胃癌手术率的提高仍需进一步开展无症状人群的筛查及高危人群的随访。

分子标志物在胃癌发病机制及转化医学研究中的应用

该项目以分子标志物为切入点,以高通量组学技术为基础,筛选出胃癌相关的分子标志物,对胃癌候选分子标志物进行生物学功能研究。结果发现,IPO-38、胃泌素、IL-33以及循环血中的FAM5C和MYLK高甲基化等胃癌血清诊断学标志物可作为胃癌早期诊断的标志物。研究还发现,FRZB、TXNL2、PHF10、MPS-1、PTP1B在胃癌组织中均呈高表达,与肿瘤细胞的增殖、分化、凋亡和侵袭等有关;胃癌细胞中AE1高表达可以将p16扣押在胞质,阻止其入核而起到原癌基因的作用;IRX1和miR-126在胃癌组织中均呈低表达,在胃癌中的作用类似抑癌基因。该研究为筛选胃癌候选标志物、开发诊断、分子靶点和预后判断等临床转化研究奠定了良好的基础,并荣获2008年国家科技进步二等奖和2012年上海市科技进步一等奖。

胃癌急性穿孔的诊断与外科治疗

目的 :探讨胃癌急性穿孔的诊断和外科治疗。方法 :对我院 1998年～ 1999年间 45例胃癌急性穿孔患者的临床资料进行回顾性分析。结果 :胃癌穿孔多见于高龄 ,均为进展期溃疡型癌 ,病理多为低分化或未分化腺癌 (37/ 45例 ,82 2 %) ,全组 45例行单纯穿孔修补 2 0例 ,姑息性胃癌切除 10例 ,胃癌根治切除 15例 ,3种术式术后并发症发生率分别为 30 %、 10 %、 13%;术后平均生存时间分别为 6 1个月、 16个月、 2 6个月 ,全组 2例死亡均为单纯穿孔修补病例。死亡原因为脏器功能衰竭和局部再穿孔。结论 :胃癌穿孔常表现为年龄偏大 ,全身情况差 ,溃疡及穿孔直径大 ,邻近器官转移或侵润等 ,术中应提高对本病的认识和警惕性 ,应积极手术治疗 ,尽可能行姑息性或根治性胃癌切除术。

胃癌急性穿孔手术治疗34例分析

目的探讨胃癌急性穿孔手术治疗方法的选择。方法对34例胃癌急性穿孔患者分别行胃远端大部分切除术(19例)、单纯穿孔修补术(9例)和胃癌根治术(6例),比较各种手术的生存期。结果治愈30例,死亡4例。术后27例获得随访,19例行胃远端大部分切除存活时间10～24个月,平均15.0个月;9例行穿孔修补术存活时间3～7个月,平均5.7个月;6例行胃癌根治术存活时间17～40个月,平均32.8个月。结论胃癌急性穿孔的早期诊断、术式的正确选择和手术时机的把握,是降低病死率,提高生存质量的重要因素,其中胃远端大部分切除术为首选。

早期胃癌的诊断及外科治疗体会（附82例临床分析）

本文回顾总结早期胃癌８２网的临床资料。１年、３年、５年随访生存率分别是１００％、９９％和９７％。认为对“高危人群”要定期检查，定期随访。胃镜检查是诊断早期胃癌的主要依据。早期胃癌手术方式应采取胃癌根治性Ｒ＿２切除手术方式。

早期胃癌的诊断及外科治疗体会──附82例临床分析

本文回顾总结早期胃癌８２例的临床资料。１年、３年、５年随访生存率分别是１００％，９９％和９７％。认为对“高危人群”要定期检查。定期随访。胃镜检查是诊断早期胃癌的主要依据。早期胃癌手术方式应采取胃癌根治住Ｒ＿２切除手术方式。