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1.
BMC Cancer ; 24(1): 1014, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148031

RESUMO

BACKGROUND: The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. METHODS: We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. RESULTS: 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p < 0.0001). Patients with greater SII-PNI scores had a poorer prognosis (p < 0.0001). The SII-PNI score was found to be an independent predictor of both overall survival (HR = 4.982, 95%CI: 1.890-10.234, p = 0.001) and disease-free survival (HR = 4.763, 95%CI: 1.994-13.903, p = 0.001) in a multivariate analysis. CONCLUSION: The clinical potential and accuracy of low-cost stratification based on SII-PNI score in forecasting tumor response and prognosis in LAGC is satisfactory.


Assuntos
Terapia Neoadjuvante , Avaliação Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/imunologia , Masculino , Feminino , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inflamação , Estado Nutricional , Estudos Prospectivos , Quimioterapia Adjuvante/métodos
2.
Int J Surg ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954670

RESUMO

BACKGROUND: Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively to sort lymph nodes (LNs) in gastric cancer patients. However, no study has compared the two tracers in gastric cancer patients. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted from January 2022 to March 2023. Patients with potentially resectable gastric cancer (cT1-4a N0/+ M0) were randomized to the CNSI or ICG group. RESULTS: This study enrolled 96 patients. Ninety patients were in the modified intention-to-treat population, including 46 patients (32 males and 14 females; mean [SD] age, 57.4 [9.4] years) in the CNSI group and 44 patients (31 males and 13 females; mean [SD] age, 60.8 [8.8] years) in the ICG group. The mean (SD) number of retrieved LNs was 69.8 (21.9) and 53.6 (17.2) in the CNSI and ICG groups, respectively (P<0.001). The mean (SD) number of retrieved micro-LNs was 19.9 (13.3) and 11.6 (9.9) in the CNSI and ICG groups, respectively (P=0.001). The mean (SD) number of metastatic LNs was 8.1 (11.9) and 5.2 (9.2) in the CNSI and ICG groups, respectively (P=0.19). CONCLUSIONS: Compared with ICG, CNSI can increase the number of LNs detected, especially micro-LNs. Both tracers have high diagnostic value for detecting metastatic LNs. CNSI-guided lymphography may be a superior method for improving the accuracy of LN dissection.

3.
Oncogene ; 43(34): 2548-2563, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39014193

RESUMO

Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.


Assuntos
Adenosina , Metástase Linfática , RNA Circular , Proteínas de Ligação a RNA , Transdução de Sinais , Neoplasias Gástricas , Fator A de Crescimento do Endotélio Vascular , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Metástase Linfática/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Transdução de Sinais/genética , Camundongos , Masculino , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Prognóstico , Feminino , Camundongos Nus
4.
J Exp Clin Cancer Res ; 43(1): 181, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937855

RESUMO

BACKGROUND: This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC). METHODS: We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC. RESULTS: Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944-0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926-1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936-1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874-1.000). CONCLUSIONS: Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.


Assuntos
Biomarcadores Tumorais , Perfilação da Expressão Gênica , Micrometástase de Neoplasia , Recidiva Local de Neoplasia , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Biópsia Líquida/métodos , Feminino , Micrometástase de Neoplasia/genética , Masculino , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Pessoa de Meia-Idade , Transcriptoma , Idoso
5.
Am J Cancer Res ; 14(5): 2124-2140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859826

RESUMO

Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.

6.
Am J Cancer Res ; 14(5): 2272-2286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859846

RESUMO

OBJECTIVE: To establish nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer liver metastasis (GCLM) patients. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database for 5,451 GCLM patients diagnosed between 2010 and 2015 were analyzed. The cohort was divided into a training set (3,815 cases) and an internal validation set (1,636 cases). External validation included 193 patients from the Fourth Hospital of Hebei Medical University and 171 patients from the People's Hospital of Shijiazhuang City, spanning 2016-2018. Multivariable Cox regression analysis identified eight independent prognostic factors for OS and CSS in GCLM patients, including age, histological type, grade, tumor size, surgery, chemotherapy, bone metastasis, and lung metastasis. Two nomogram models were developed based on these factors and evaluated using time-dependent receiver operating characteristic curve analysis, calibration curves, and decision curve analysis. RESULTS: Internal validation showed that the nomogram models outperformed the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system in predicting 1-year, 2-year, and 3-year OS and CSS in GCLM patients (1-year OS: 0.801 vs. 0.593, P < 0.001; 1-year CSS: 0.807 vs. 0.598, P < 0.001; 2-year OS: 0.803 vs. 0.630, P < 0.001; 2-year CSS: 0.802 vs. 0.633, P < 0.001; 3-year OS: 0.824 vs. 0.691, P < 0.001; 3-year CSS: 0.839 vs. 0.692, P < 0.001). CONCLUSION: This study developed and validated nomogram models using SEER database data to predict OS and CSS in GCLM patients. These models offer improved prognostic accuracy over traditional staging systems, aiding in clinical decision-making.

7.
Ann Med ; 56(1): 2319749, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38733306

RESUMO

PURPOSE: Remnant cholesterol (RC) is the cholesterol content of triglyceride-rich lipoproteins. This study aimed to investigate the association between RC levels and kidney stones in U.S. adults. METHODS: Data were obtained from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES). A total of 10,551 participants with complete data were included and analyzed in this study. Univariate and multivariate logistic regression analysis, restricted cubic spline function, subgroup analysis and mediation analysis were preformed to estimate the independent relationship between RC levels and kidney stones. RESULTS: Participants with stone formation had higher levels of RC than those with without stone formation (25.78 ± 13.83 vs 23.27 ± 13.04, p< 0.001). The results of logistic regression analysis and dose-response risk curves revealed a positive nonlinear association between RC levels and risk of kidney stones [univariate: adjusted odds ratio (aOR) =2.388, 95% CI: 1.797-3.173, p< 0.001; multivariate: aOR = 1.424, 95% CI: 1.050-1.929, p = 0.023]. Compared with the discordantly low RC group, the discordantly high RC group was associated with increased risk of kidney stones (aOR = 1.185, 95% CI: 1.013-1.386, p= 0.034). Similar results were demonstrated according to the discordance of different clinical cut points. And metabolic syndrome parameters and vitamin D levels parallelly mediated the association between RC and kidney stone risk. CONCLUSIONS: Higher RC levels were independently associated with an increased risk of kidney stone incidence.


Higher remnant cholesterol levels were independently associated with an increased risk of kidney stone incidence.


Assuntos
Colesterol , Cálculos Renais , Inquéritos Nutricionais , Triglicerídeos , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Colesterol/sangue , Estados Unidos/epidemiologia , Fatores de Risco , Triglicerídeos/sangue , Idoso , Modelos Logísticos , Estudos Transversais
8.
World J Gastrointest Surg ; 16(4): 1109-1120, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38690052

RESUMO

BACKGROUND: The incidence of gastric cancer has significantly increased in recent years. Surgical resection is the main treatment, but the method of digestive tract reconstruction after gastric cancer surgery remains controversial. In the current study, we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after surgery. To this end, we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction (DTR) and esophageal jejunum Roux-en-Y reconstruction (RY). AIM: To explore the application effect of DTR in total laparoscopic radical total gastrectomy (TLTG) and evaluate its safety and efficacy. METHODS: We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January 2023. Among them, 35 cases were treated with DTR, and the remaining 42 cases were treated with traditional RY. After 1:1 propensity score matching, the cases were grouped into 31 cases per group, with evenly distributed data. The clinical characteristics and short- and long-term clinical outcomes of the two groups were statistically analyzed. RESULTS: The two groups showed no significant differences in basic data, intraoperative blood loss, number of lymph node dissections, first defecation time after operation, postoperative hospital stay, postoperative complications, and laboratory examination results on the 1st, 3rd, and 5th days after operation. The operation time of the DTR group was longer than that of the RY group [(307.58 ± 65.14) min vs (272.45 ± 62.09) min, P = 0.016], but the first intake of liquid food in the DTR group was shorter than that in the RY group [(4.45 ± 1.18) d vs (6.0 ± 5.18) d, P = 0.028]. The incidence of reflux heartburn (Visick grade) and postoperative gallbladder disease in the DTR group was lower than that in the RY group (P = 0.033 and P = 0.038). Although there was no significant difference in body weight, hemoglobin, prealbumin, and albumin between the two groups at 1,3 and 6 months after surgery, the diet of patients in the DTR group was better than that in the RY group (P = 0.031). CONCLUSION: The clinical effect of DTR in TLTG is better than that of RY, indicating that it is a more valuable digestive tract reconstruction method in laparoscopic gastric cancer surgery.

9.
Cost Eff Resour Alloc ; 22(1): 38, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711056

RESUMO

BACKGROUND: Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. METHOD: The data were extracted from the Fourth Hospital of Hebei Medical University's (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann-Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. RESULTS: Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241). CONCLUSION: The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.

10.
Am J Cancer Res ; 14(4): 1747-1767, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726268

RESUMO

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

11.
Am J Cancer Res ; 14(4): 1675-1684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726280

RESUMO

Mitoxantrone Hydrochloride Injection for Tracing (MHI), a modified new drug marketed in China, has been approved by the National Medical Products Administration for lymph node tracing in thyroid cancer and sentinel lymph node biopsy in breast cancer. This single-center, single-blind, dose-escalation phase I clinical trial aimed to investigate the safety of MHI on lymph node tracing in gastric cancer. In this study, four dose groups (1.0 mL, 1.5 mL, 2.0 mL, and 3.0 mL) with 3 gastric cancer patients in each group were set. The safety, tolerability, pharmacokinetics and preliminary efficacy of different doses were investigated. Results showed that none of the patients experienced dose-limiting toxicity or developed serious adverse events or adverse drug reactions. Pharmacokinetic analyses revealed minimal absorption of the tracer, resulting in low and transient blood drug concentrations across all participants. The mean time to peak concentration was (0.561 ± 0.3728) h (with mean peak concentration (Cmax) of 10.300 ng/mL), (0.500 ± 0.0167) h (mean Cmax of 13.687 ng/mL), (0.494 ± 0.0096) h (mean Cmax of 30.933 ng/mL), and (0.661 ± 0.2791) h (mean Cmax of 21.067 ng/mL) in the 1.0 mL, 1.5 mL, 2.0 mL, and 3.0 mL dose groups, respectively. The mean lymph node staining rates were 21.0%, 24.7%, 32.5%, and 44.5%, and the mean metastatic lymph node staining rates were 20.6%, 36.1%, 42.4%, and 21.0% in each group. This study confirmed that MHI was safe, well-tolerated, and had low systemic effects when used for lymphatic tracing of gastric cancer, and the tracing effect was better in the 3 mL dose group. This trail was registered on the website of Centre for Drug Evaluation State Drug and Food Administration (http://www.chinadrugtrials.org.cn/index.html) with the name of clinical study of lymphatic tracer in lymph node tracing of gastric cancer, the code was CTR20201906.

12.
Abdom Radiol (NY) ; 49(7): 2165-2176, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38727742

RESUMO

PURPOSE: Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. METHODS: This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. RESULTS: Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. CONCLUSION: Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.


Assuntos
Nomogramas , Neoplasias Gástricas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Idoso , Instabilidade de Microssatélites , Adulto , Medição de Risco , Idoso de 80 Anos ou mais , Meios de Contraste
13.
Mol Carcinog ; 63(7): 1378-1391, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38656643

RESUMO

Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer (GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-ß1/SMAD2/3 signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, and lymph node (LN) metastasis in GC. Experiments using a popliteal LN metastasis model in BALB/c nude mice demonstrated that miR-431-5p significantly reduced popliteal LN metastasis. Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-ß1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.


Assuntos
Regulação Neoplásica da Expressão Gênica , Linfangiogênese , Metástase Linfática , Camundongos Endogâmicos BALB C , MicroRNAs , Neovascularização Patológica , Transdução de Sinais , Proteína Smad2 , Proteína Smad3 , Neoplasias Gástricas , Fator de Crescimento Transformador beta1 , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Animais , MicroRNAs/genética , Linfangiogênese/genética , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neovascularização Patológica/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Proteína Smad3/metabolismo , Proteína Smad3/genética , Proteína Smad2/metabolismo , Proteína Smad2/genética , Camundongos Nus , Masculino , Feminino , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Prognóstico , Pessoa de Meia-Idade , Angiogênese
14.
Nutrition ; 123: 112408, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38513525

RESUMO

BACKGROUND: Sarcopenia, defined as decreased muscle mass and function, correlates with postoperative morbidity and mortality in cancer surgery. However, sarcopenia's impact specifically following robotic gastrectomy for gastric cancer has not been clearly defined. This study aimed to determine the influence of sarcopenia on short- and long-term clinical outcomes after robotic gastrectomy for gastric cancer. METHODS: This retrospective study analyzed 381 gastric cancer patients undergoing robotic gastrectomy. Sarcopenia was diagnosed by preoperative computed tomography (CT) body composition analysis. Propensity score matching created 147 pairs of sarcopenia and nonsarcopenia patients for comparison. Outcomes included postoperative complications, survival, inflammatory markers, length of stay, intensive care unit (ICU) transfer, and readmissions. RESULTS: Sarcopenia patients exhibited significantly higher rates of overall (53.7% versus 21.1%, P < 0.001), serious (12.9% versus 4.1%, P = 0.007), and grade III-IV complications compared to nonsarcopenia pairs after matching. Sarcopenia independently predicted reduced 3-years overall (HR = 2.53, 95% CI: 1.19-5.40, P = 0.016) and disease-free survival (HR = 1.99, 95% CI: 1.09-3.66, P = 0.026). Sarcopenia patients also showed heightened postoperative leukocyte, neutrophil, platelet, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte to lymphocyte ratio (MLR) levels alongside suppressed lymphocytes, monocytes, and neutrophil to lymphocyte ratio (NLR). CONCLUSION: Preoperative sarcopenia is correlated with increased postoperative complications and poorer long-term survival in gastric cancer patients undergoing robotic gastrectomy. Sarcopenia assessment can optimize preoperative risk stratification and perioperative management in this population.


Assuntos
Gastrectomia , Complicações Pós-Operatórias , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Sarcopenia , Neoplasias Gástricas , Humanos , Sarcopenia/etiologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Masculino , Feminino , Estudos Retrospectivos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso , Pessoa de Meia-Idade , Prognóstico , Período Pré-Operatório , Tempo de Internação/estatística & dados numéricos
15.
Eur J Clin Invest ; 54(8): e14201, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38533747

RESUMO

BACKGROUND: Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy. METHODS: This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival. RESULTS: Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, p < 0.001) and severe complications (12.4% vs. 4.9%, p < 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all p < 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57-5.20, p = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51-15.27, p = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, p = 0.015) and disease-free survival (80.3% vs. 88.4%, p=0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32-6.08, p=0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01-3.30, p=0.032). CONCLUSION: Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification.


Assuntos
Gastrectomia , Complicações Pós-Operatórias , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Gastrectomia/efeitos adversos , Masculino , Feminino , Complicações Pós-Operatórias/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Readmissão do Paciente/estatística & dados numéricos , Sarcopenia/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem
16.
Front Oncol ; 13: 1201928, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841441

RESUMO

Background: Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients. Methods/design: This is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification. Discussion: This study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner. Clinical trial registration: http://clinicaltrials.gov/, identifier NCT05410847.

17.
Int J Surg ; 109(12): 4000-4008, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37678277

RESUMO

BACKGROUND: Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone. MATERIALS AND METHODS: Three hundred patients younger than 60 years with potentially resectable advanced gastric cancer (cT3-4, Nany, M0) were enrolled in this randomized controlled clinical trial between November 2014 and June 2018. The primary endpoint of the study was the pathological complete response (pCR) rate. Secondary endpoints included 3-year overall survival (OS), 3-year disease-free survival. RESULTS: In total, 280 patients (93 in the DOX group, 92 in the XELOX group, and 95 in the surgery group) were included in the per-protocol analysis. The DOX group demonstrated a significantly higher pCR rate compared to the XELOX group (16.1 vs. 4.3%, P =0.008). For patients with intestinal type, the DOX group exhibited significantly higher rates of both pCR and major pathological response compared to the XELOX group ( P =0.007, P <0.001). The 3-year OS rates of the DOX group, the XELOX group and the surgery group were 56.9, 44.6, and 34.7%, respectively. The 3-year disease-free survival rates were 45.2, 40.2, and 28.4%, respectively. The neoadjuvant DOX regimen demonstrated a significant improvement in the 3-year OS of patients compared to the neoadjuvant XELOX regimen ( P =0.037). CONCLUSION: The neoadjuvant DOX regimen has shown the potential to increase the pCR rate and improve the prognosis of patients with advanced gastric cancer who are under 60 years old.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Pessoa de Meia-Idade , Capecitabina/uso terapêutico , Neoplasias Gástricas/cirurgia , Docetaxel/uso terapêutico , Terapia Neoadjuvante , Oxaliplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adenocarcinoma/cirurgia , Fluoruracila
19.
Eur Radiol ; 33(12): 9275-9285, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37414883

RESUMO

OBJECTIVE: Accurate prediction of preoperative occult peritoneal metastasis (OPM) is critical to selecting appropriate therapeutic regimen for gastric cancer (GC). Considering the clinical practicability, we develop and validate a visible nomogram that integrates the CT images and clinicopathological parameters for the individual preoperative prediction of OPM in GC. METHODS: This retrospective study included 520 patients who underwent staged laparoscopic exploration or peritoneal lavage cytology (PLC) examination. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of OPM risk. The performance of the model was detected by using ROC, accuracy, and C-index. The bootstrap resampling method was considered internal validation of the model. The Delong test was used to evaluate the difference in AUC between the two models. RESULTS: Grade 2 mural stratification, tumor thickness, and the Lauren classification diffuse were significant predictors of OPM (p < 0.05). The nomogram of these three factors (compared with the original model) showed a higher predictive effect (p < 0.001). The area under the curve (AUC) of the model was 0.830 (95% CI 0.788-0.873), and the internally validated AUC of 1000 bootstrap samples was 0.826 (95% CI 0.756-0.870). The sensitivity, specificity, and accuracy were 76.0%, 78.8%, and 78.3%, respectively. CONCLUSIONS: CT phenotype-based nomogram demonstrates favorable discrimination and calibration, and it can be conveniently used for preoperative individual risk rating of OPM in GC. CLINICAL RELEVANCE STATEMENT: In this study, the preoperative OPM prediction model based on CT images (mural stratification, tumor thickness) combined with pathological parameters (the Lauren classification) showed excellent predictive ability in GC, and it is also suitable for clinicians to use rather than limited to professional radiologists. KEY POINTS: • Nomogram based on CT image analysis can effectively predict occult peritoneal metastasis in gastric cancer (training area under the curve (AUC) = 0.830 and bootstrap AUC = 0.826). • Nomogram model combined with CT features performed better than the original model (established using only clinicopathological parameters) in differentiating occult peritoneal metastasis of gastric cancer.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Neoplasias Peritoneais/diagnóstico , Citologia , Nomogramas , Tomografia Computadorizada por Raios X/métodos
20.
BMC Cancer ; 23(1): 536, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308852

RESUMO

BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.


Assuntos
Carcinoma , Neoplasias Gástricas , Humanos , Metástase Linfática , Estudos Retrospectivos , Suplementos Nutricionais
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