Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient clas...Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.展开更多
AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activ...AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG.展开更多
Laparoscopic gastrectomy has been widely accepted as a standard alternative for the treatment of early-stage gastric adenocarcinoma because of its favorable shortterm outcomes. Although controversies exist, such as es...Laparoscopic gastrectomy has been widely accepted as a standard alternative for the treatment of early-stage gastric adenocarcinoma because of its favorable shortterm outcomes. Although controversies exist, such as establishing clear indications, proper preoperative staging, and oncologic safety, experienced surgeons and institutions have applied this approach, along with various types of function-preserving surgery, for the treatment of advanced gastric cancer. With technical advancement and the advent of state-of-the-art instruments, indications for laparoscopic gastrectomy are expected to expand as far as locally advanced gastric cancer. Laparoscopic gastrectomy appears to be promising; however, scientific evidence necessary to generalize this approach to a standard treatment for all relevant patients and care providers remains to be gathered. Several multicenter, prospective randomized trials in high-incidence countries are ongoing, and results from these trials will highlight the short- and long-term outcomes of the approach. In this review, we describe up-to-date findings and critical issues regarding laparoscopic gastrectomy for gastric cancer.展开更多
AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010,...AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.展开更多
AIM:To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection.METHODS:Using a prospective,single-blind,placebocontrolled design,patients...AIM:To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection.METHODS:Using a prospective,single-blind,placebocontrolled design,patients with advanced gastric cancer were randomized into a study group(n=61)and a control group(n=59).Patients in the study group were given somatostatin for 5-7 d starting 6 h after the operation,and patients in the control group were given normal saline.Preoperative and nonoperative complications in the perioperative period,as well as differenttypes of postoperative drainage in the two groups were compared.RESULTS:There was no significant difference between the study group and the control group for preoperative clinicopathological indicators.We found no significant difference between the two groups for the overall incidence of complications,but a lower percentage of peritoneal effusion was observed in the treatment group(1.6%vs 10.2%,P<0.05).There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula.However,there were significant differences in the amylase concentration in drainage fluid,volume and duration of drainage,volume and duration of chylous fistula and peritoneal drainage,and volume and duration of gastric tube drainage.The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred.CONCLUSION:Postoperative somatostatin reduces volume and duration of surgical drainage and related complications.Somatostatin may improve safety of gastric cancer surgery,reducing postoperative complications and promoting recovery.展开更多
Objective:Recent studies have highlighted the distinct value of tertiary lymphoid structure(TLS)for immunotherapeutic response prediction.However,it remains unclear whether TLS could play such roles in gastric cancer(...Objective:Recent studies have highlighted the distinct value of tertiary lymphoid structure(TLS)for immunotherapeutic response prediction.However,it remains unclear whether TLS could play such roles in gastric cancer(GC).Methods:In this study,tumor tissue slices from 292 GC patients from Zhongshan Hospital were firstly reviewed to explore the correlation between TLS and clinical characteristics.Subsequently,we curated 38 reported genes that may function as triggers of TLS and performed consensus molecular subtyping in public RNA-seq datasets to determine TLS patterns in GC.Based on the differentially expressed genes acquired from two TLS patterns,we quantified TLS-related genes on the principal component analysis(PCA)algorithm to develop TLS score.A Zhongshan immunotherapy cohort including 13 patients who received programmed cell death 1(PD1)blockade therapy was established to conduct RNA sequencing analysis and multiplex immunohistochemistry(mIHC)tests using formalin-fixed and paraffin-embedded(FFPE)tissues.The corresponding TLS score and immune cell counts were further compared based on therapeutic response variations.Results:Mature TLS was revealed as an independent prognostic factor in 292 GC patients.Patients with higher TLS score was characterized by prolonged survival time and superior response to immunotherapy.TLS score was correlated with immunotherapy-related characters,such as microsatellite instability(MSI)and tumor mutation burden(TMB).In addition,RNA-seq data analysis in the Zhongshan immunotherapy cohort indicated that a higher TLS score was correlated with a superior response to PD1 blockade therapy.mIHC tests also revealed that PD1+CD8+T cell counts were significantly increased in the high-TLS score group.Conclusions:This study highlighted that TLS was significantly associated with immune landscape diversity and complexity.Quantitatively evaluating TLS patterns of individual tumor will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies.展开更多
Gastric cancer is one of the most common malignant tumors worldwide.China is a large country in which gastric cancer ranks among the top 3 malignant tumors in terms of incidence,and related morbidity and mortality1.In...Gastric cancer is one of the most common malignant tumors worldwide.China is a large country in which gastric cancer ranks among the top 3 malignant tumors in terms of incidence,and related morbidity and mortality1.In the past 20 years,China has made the most outstanding achievements in the diagnosis and treatment of gastric cancer among countries worldwide.The overall 5-year survival rate of patients in China has increased by nearly 10%2.However,early gastric cancer accounts for only 20%of clinically confirmed cases,the overall effects of therapies for gastric cancer still must be improved3.The REGATTA study has confirmed that palliative surgery cannot improve the long-term survival of patients with stage IV gastric cancer4.展开更多
BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and c...BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype of GISTs.展开更多
In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developi...In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developing detection and treatment methods should continue.The diagnostic path typically begins with learning the medical history of a patient;this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy.Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization.Thus,there is a need for novel cancer detection methods such as liquid biopsy,elastography,synthetic biosensors,fluorescence imaging,and reflectance confocal microscopy.Conventional therapeutic methods,although still common in clinical practice,pose many limitations and are unsatisfactory.Nowadays,there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy,exosome-based therapy,nanotechnology,dendritic cells,chimeric antigen receptors,immune checkpoint inhibitors,natural product-based therapy,tumor-treating fields,and photodynamic therapy.The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions.As evidenced,modern methods are not without drawbacks;there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity,specificity,safety,and efficacy.Nevertheless,an appropriate route has been taken,as confirmed by the approval of some modern methods by the Food and Drug Administration.展开更多
AIM To investigate the clinical significance of preoperative systemic immune-inflammation index(SII) in patients with colorectal cancer(CRC). METHODS A retrospective analysis of 1383 cases with CRC was performed follo...AIM To investigate the clinical significance of preoperative systemic immune-inflammation index(SII) in patients with colorectal cancer(CRC). METHODS A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII =(P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR) in patients with CRC.RESULTS The optimal cut-off point for SII was defined as 340. The overall survival(OS) and disease-free survival(DFS) were better in patients with low NLR, PLR, and SII(P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics(ROC) curve for SII(0.707) was larger than those for NLR(0.602) and PLR(0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.展开更多
AIM: To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer (HNPCC) in suspected Chinese patients. METHODS: Five independent Chinese ki...AIM: To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer (HNPCC) in suspected Chinese patients. METHODS: Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC). Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool (BLAST), and tested in the corresponding family members by direct DNA sequencing. RESULTS: Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A→G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC (HNPCCS) kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A→G was identified in the HNP2 kindred's proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION: Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.展开更多
Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The curre...Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The current body of research on Britanin includes thirty papers predominantly related to neoplasms,the majority of which are gastrointestinal tumors that have not been summarized before.To drive academic debate,the present paper reviews the available research on Britanin in gastrointestinal tumors.It also outlines novel research directions using data not directly concerned with the digestive system,but which could be adopted in future gastrointestinal research.Britanin was found to counteract liver,colorectal,pancreatic,and gastric tumors,by regulating proliferation,apoptosis,autophagy,immune response,migration,and angiogenesis.As confirmed in pancreatic,gastric,and liver cancer,its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation,as well as Bcl-2-associated X protein upregulation.Moreover,it has been found to induce the Akt kinase and Forkhead box O1 axis,activate the AMP-activated protein kinase pathway,elevate interleukin-2 and peroxisome proliferator-activated receptor-γlevels,reduce interleukin-10,as well as downregulate matrix metalloproteinase-9,Twist family bHLH transcription factor 1,and cyclooxygenase-2.It also inhibits Myc–HIF1αinteraction and programmed death ligand 1 transcription by interrupting the Ras/RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling.Future research should aim to unravel the link between Britanin and acetylcholinesterase,mast cells,osteolysis,and ischemia,as compelling data have been provided by studies outside the gastrointestinal context.Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells,while still being effective against the latter,further in-depth studies with the use of animal models are merited.The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent,which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.展开更多
基金partial financial support provided by Novomics (Seoul, Korea)
文摘Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.
基金Supported by National Natural Science Foundation of China, Grant, No. 30571833Natural Science Foundation of Guangdong Province, 05001785China Postdoctoral Science Foundation 20100470963
文摘AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG.
基金Supported by ETRI R&D Program(14ZC1400The Development of a Realistic Surgery Rehearsal System based on Patient Specific Surgical Planning)funded by the Government of South Korea
文摘Laparoscopic gastrectomy has been widely accepted as a standard alternative for the treatment of early-stage gastric adenocarcinoma because of its favorable shortterm outcomes. Although controversies exist, such as establishing clear indications, proper preoperative staging, and oncologic safety, experienced surgeons and institutions have applied this approach, along with various types of function-preserving surgery, for the treatment of advanced gastric cancer. With technical advancement and the advent of state-of-the-art instruments, indications for laparoscopic gastrectomy are expected to expand as far as locally advanced gastric cancer. Laparoscopic gastrectomy appears to be promising; however, scientific evidence necessary to generalize this approach to a standard treatment for all relevant patients and care providers remains to be gathered. Several multicenter, prospective randomized trials in high-incidence countries are ongoing, and results from these trials will highlight the short- and long-term outcomes of the approach. In this review, we describe up-to-date findings and critical issues regarding laparoscopic gastrectomy for gastric cancer.
基金Supported by National Natural Science Foundation of China,No. 30700805 and 81272643Project 5010 from Sun Yat-Sen University, No. 20100816Young Teacher Training Project of SunYat-Sen University, No. 09ykpy49
文摘AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.
基金Supported by Guangdong Province Science and Technology Plan Project,No.2011b031800240 and No.2012b031800389Guangdong Province Natural Science Fund,No.520130 10015528
文摘AIM:To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection.METHODS:Using a prospective,single-blind,placebocontrolled design,patients with advanced gastric cancer were randomized into a study group(n=61)and a control group(n=59).Patients in the study group were given somatostatin for 5-7 d starting 6 h after the operation,and patients in the control group were given normal saline.Preoperative and nonoperative complications in the perioperative period,as well as differenttypes of postoperative drainage in the two groups were compared.RESULTS:There was no significant difference between the study group and the control group for preoperative clinicopathological indicators.We found no significant difference between the two groups for the overall incidence of complications,but a lower percentage of peritoneal effusion was observed in the treatment group(1.6%vs 10.2%,P<0.05).There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula.However,there were significant differences in the amylase concentration in drainage fluid,volume and duration of drainage,volume and duration of chylous fistula and peritoneal drainage,and volume and duration of gastric tube drainage.The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred.CONCLUSION:Postoperative somatostatin reduces volume and duration of surgical drainage and related complications.Somatostatin may improve safety of gastric cancer surgery,reducing postoperative complications and promoting recovery.
基金supported by grants from the National Natural Science Foundation of China(No.82172803 and No.82072679)the 2020 Zhongshan Hospital Clinical Research Special Fund(No.2020ZSLC15)。
文摘Objective:Recent studies have highlighted the distinct value of tertiary lymphoid structure(TLS)for immunotherapeutic response prediction.However,it remains unclear whether TLS could play such roles in gastric cancer(GC).Methods:In this study,tumor tissue slices from 292 GC patients from Zhongshan Hospital were firstly reviewed to explore the correlation between TLS and clinical characteristics.Subsequently,we curated 38 reported genes that may function as triggers of TLS and performed consensus molecular subtyping in public RNA-seq datasets to determine TLS patterns in GC.Based on the differentially expressed genes acquired from two TLS patterns,we quantified TLS-related genes on the principal component analysis(PCA)algorithm to develop TLS score.A Zhongshan immunotherapy cohort including 13 patients who received programmed cell death 1(PD1)blockade therapy was established to conduct RNA sequencing analysis and multiplex immunohistochemistry(mIHC)tests using formalin-fixed and paraffin-embedded(FFPE)tissues.The corresponding TLS score and immune cell counts were further compared based on therapeutic response variations.Results:Mature TLS was revealed as an independent prognostic factor in 292 GC patients.Patients with higher TLS score was characterized by prolonged survival time and superior response to immunotherapy.TLS score was correlated with immunotherapy-related characters,such as microsatellite instability(MSI)and tumor mutation burden(TMB).In addition,RNA-seq data analysis in the Zhongshan immunotherapy cohort indicated that a higher TLS score was correlated with a superior response to PD1 blockade therapy.mIHC tests also revealed that PD1+CD8+T cell counts were significantly increased in the high-TLS score group.Conclusions:This study highlighted that TLS was significantly associated with immune landscape diversity and complexity.Quantitatively evaluating TLS patterns of individual tumor will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies.
文摘Gastric cancer is one of the most common malignant tumors worldwide.China is a large country in which gastric cancer ranks among the top 3 malignant tumors in terms of incidence,and related morbidity and mortality1.In the past 20 years,China has made the most outstanding achievements in the diagnosis and treatment of gastric cancer among countries worldwide.The overall 5-year survival rate of patients in China has increased by nearly 10%2.However,early gastric cancer accounts for only 20%of clinically confirmed cases,the overall effects of therapies for gastric cancer still must be improved3.The REGATTA study has confirmed that palliative surgery cannot improve the long-term survival of patients with stage IV gastric cancer4.
基金Supported by the National Natural Science Foundation of China Program Grant,No.82203108China Postdoctoral Science Foundation,No.2022M722275+1 种基金Beijing Bethune Charitable Foundation,No.WCJZL202105Beijing Xisike Clinical Oncology Research Foundation,No.Y-zai2021/zd-0185。
文摘BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype of GISTs.
文摘In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developing detection and treatment methods should continue.The diagnostic path typically begins with learning the medical history of a patient;this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy.Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization.Thus,there is a need for novel cancer detection methods such as liquid biopsy,elastography,synthetic biosensors,fluorescence imaging,and reflectance confocal microscopy.Conventional therapeutic methods,although still common in clinical practice,pose many limitations and are unsatisfactory.Nowadays,there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy,exosome-based therapy,nanotechnology,dendritic cells,chimeric antigen receptors,immune checkpoint inhibitors,natural product-based therapy,tumor-treating fields,and photodynamic therapy.The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions.As evidenced,modern methods are not without drawbacks;there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity,specificity,safety,and efficacy.Nevertheless,an appropriate route has been taken,as confirmed by the approval of some modern methods by the Food and Drug Administration.
基金Supported by National Nature Science Foundation of China,No.81672343 and No.81372341Guangdong Province Natural Science Fund of China,No.2014A030310111Guangdong Science and Technology Plan Project of China,No.2013B021800131and No.201604020003
文摘AIM To investigate the clinical significance of preoperative systemic immune-inflammation index(SII) in patients with colorectal cancer(CRC). METHODS A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII =(P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR) in patients with CRC.RESULTS The optimal cut-off point for SII was defined as 340. The overall survival(OS) and disease-free survival(DFS) were better in patients with low NLR, PLR, and SII(P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics(ROC) curve for SII(0.707) was larger than those for NLR(0.602) and PLR(0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.
基金The Special Funds of China Education Ministry for Returnees, No. 2003-14
文摘AIM: To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer (HNPCC) in suspected Chinese patients. METHODS: Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC). Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool (BLAST), and tested in the corresponding family members by direct DNA sequencing. RESULTS: Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A→G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC (HNPCCS) kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A→G was identified in the HNP2 kindred's proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION: Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.
文摘Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The current body of research on Britanin includes thirty papers predominantly related to neoplasms,the majority of which are gastrointestinal tumors that have not been summarized before.To drive academic debate,the present paper reviews the available research on Britanin in gastrointestinal tumors.It also outlines novel research directions using data not directly concerned with the digestive system,but which could be adopted in future gastrointestinal research.Britanin was found to counteract liver,colorectal,pancreatic,and gastric tumors,by regulating proliferation,apoptosis,autophagy,immune response,migration,and angiogenesis.As confirmed in pancreatic,gastric,and liver cancer,its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation,as well as Bcl-2-associated X protein upregulation.Moreover,it has been found to induce the Akt kinase and Forkhead box O1 axis,activate the AMP-activated protein kinase pathway,elevate interleukin-2 and peroxisome proliferator-activated receptor-γlevels,reduce interleukin-10,as well as downregulate matrix metalloproteinase-9,Twist family bHLH transcription factor 1,and cyclooxygenase-2.It also inhibits Myc–HIF1αinteraction and programmed death ligand 1 transcription by interrupting the Ras/RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling.Future research should aim to unravel the link between Britanin and acetylcholinesterase,mast cells,osteolysis,and ischemia,as compelling data have been provided by studies outside the gastrointestinal context.Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells,while still being effective against the latter,further in-depth studies with the use of animal models are merited.The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent,which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.