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Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.
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Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.
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Neoplasias Retais , Reto , Humanos , Reto/patologia , Estudos Prospectivos , Qualidade de Vida , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H. pylori eradication on AG and IM. METHODS: We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM. RESULTS: Twenty articles with a total of 5242 participants were included in this meta-analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD -0.36; 95% CI: -0.52, -0.19, p < 0.01), GA score in the corpus (WMD -0.35; 95% CI: -0.52, -0.19, p < 0.01), IM score in the antrum (WMD -0.16; 95% CI: -0.26, -0.07, p < 0.01) and IM score in the corpus (WMD -0.20; 95% CI: -0.37, -0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow-up time. Although Publication bias was observed for AG, the association remained significant after trim-and-fill adjustment. CONCLUSIONS: H. pylori eradication could significantly improve AG and IM at early stage.
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Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Humanos , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Atrofia , Metaplasia/complicaçõesRESUMO
Rare-earth-doped silica-based composite glasses (Re-SCGs) are widely used as high-quality laser gain media in defense, aerospace, energy, power, and medical applications. The variable regional chemical environments of Re-SCGs can induce new photoluminescence properties of rare-earth ions but can cause the selective aggregation of rare-earth ions, limiting the application of Re-SCGs in the field of high-power lasers. Here, topological engineering is proposed to adjust the degree of cross-linking of phase-separation network chains in Re-SCGs. A combination of experimental and theoretical characterization techniques suggested that the selective aggregation of rare-earth ions originates from the formation of phase-separated structures in glasses. The decomposition of nanoscale phase separation structures to the sub-nanometer scale, enabled by incorporating Al3+ ions, not only maintains the high luminescence efficiency of rare earth ions but also increases light transmittance and reduces light scattering. Furthermore, our investigation encompassed the exploration of the inhibitory mechanism of Al3+ ions on phase-separation structures, as well as their influence on the spectral characteristics of Re-SCGs. This work provides a new design concept for composite glass materials doped with rare-earth ions and could broaden their application in the field of high-power lasers.
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AIM: For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. METHOD: The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. DISCUSSION: The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.
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Nd3+-doped three-level (4F3/2-4I9/2) fiber lasers with wavelengths in the range of 850-950â nm are of considerable interest in applications such as bio-medical imaging and blue and ultraviolet laser generation. Although the design of a suitable fiber geometry has enhanced the laser performance by suppressing the competitive four-level (4F3/2-4I11/2) transition at â¼1 µm, efficient operation of Nd3+-doped three-level fiber lasers still remains a challenge. In this study, taking a developed Nd3+-doped silicate glass single-mode fiber as gain medium, we demonstrate efficient three-level continuous-wave lasers and passively mode-locked lasers with a gigahertz (GHz) fundamental repetition rate. The fiber is designed using the rod-in-tube method and has a core diameter of 4 µm with a numerical aperture of 0.14. In a short 4.5-cm-long Nd3+-doped silicate fiber, all-fiber CW lasing in the range of 890 to 915â nm with a signal-to-noise ratio (SNR) greater than 49â dB is achieved. Especially, the laser slope efficiency reaches 31.7% at 910â nm. Furthermore, a centimeter-scale ultrashort passively mode-locked laser cavity is constructed and ultrashort pulse at 920â nm with a highest GHz fundamental repetition is successfully demonstrated. Our results confirm that Nd3+-doped silicate fiber could be an alternative gain medium for efficient three-level laser operation.
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BACKGROUND: The extent of lymphadenectomy in patients with pT2 colorectal cancer (CRC) remains controversial. This study aimed to elucidate the effects of D3 and D2 lymph node dissection (LND) on survival in patients diagnosed with pT2 CRC. METHODS: This was a retrospective cohort study from a high-volume cancer center in Japan. From April 2007 to December 2020, 6273 patients with primary CRC were included in the study; among these, 616 patients diagnosed with pT2 CRC underwent radical colorectal resection. Propensity score matching (PSM) was applied to balance potential confounding factors, and a total of 104 matched pairs were extracted from the entire cohort. Independent risk factors associated with prognosis were determined by Cox regression analysis. The main outcome measures were overall survival (OS) and cancer-specific survival (CSS). RESULTS: Before PSM, there was a statistically significant difference across the cohort in OS and CSS (p = 0.000 and 0.013) between D3 and D2 LND groups; the estimated hazard ratio (HR) was 2.2 (95% confidence interval (CI), 1.1-4.4, p = 0.031) for OS in the D3 LND and 4.4 (95% CI, 1.7 to 11, p = 0.0027) for CSS (p = 0.013). There was also a significant difference (p = 0.024) in OS between the D3 and D2 LND groups in the matched cohort, with an estimated HR for OS of 3.3 (95% CI, 1.2 to 9.1, p = 0.024) and an estimated HR for CSS of 7.2 (95% CI, 1.6 to 33, p = 0.011). CONCLUSIONS: D3 LND had a significant survival advantage in the treatment of pT2 CRC. The results of this study provide a theoretical basis for the application of D3 LND in radical surgery for preoperative T2 CRC.
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Neoplasias Colorretais , Excisão de Linfonodo , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Excisão de Linfonodo/efeitos adversos , Prognóstico , Neoplasias Colorretais/patologia , Linfonodos/cirurgia , Linfonodos/patologiaRESUMO
PURPOSE: This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA. METHODS: The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period. RESULTS: Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment (P = 0.237). CONCLUSIONS: Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , China , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Prognóstico , Estados UnidosRESUMO
BACKGROUND: Currently, young colon cancer (CC) patients continue to increase and represent a heterogeneous patient group. The aim of this study was to explore the optimal minimum lymph node count after CC resection for young patients. METHODS: We performed a comprehensive search of the Surveillance, Epidemiology, and End Results (SEER) database, 2360 CC patients aged from 20 to 40 were analyzed. X-tile was used to determine the optimal cut-off point of lymph node based on survival outcomes of young patients. The cancer specific survival (CSS) was estimated with Kaplan-Meier method, the Cox proportional hazards regression model was used to analyse independent prognostic factors and exact 95% confidence intervals (CIs). RESULTS: Using X-tile analysis, 22-node measure was identified as the optimal choice for CC patients aged < 40. The 5-year CSS were 85.8% and 80.9% for patients examining ≥22 nodes and < 22 nodes. Furthermore, we identified that examining < 22 nodes was an independent adverse prognostic factor in patients aged < 40. In addition, the revised 22-node measure could examine more positive nodes than the standard 12-node measure in young patients. CONCLUSIONS: For young colon cancer patients, the lymph node examination should be differently evaluated. We suggest that 22-node measure may be more suitable for CC patients aged < 40. TRIAL REGISTRATION: Retrospectively registered.
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Neoplasias do Colo/patologia , Excisão de Linfonodo/métodos , Metástase Linfática/diagnóstico , Estadiamento de Neoplasias/métodos , Adulto , Neoplasias do Colo/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Adulto JovemRESUMO
PURPOSE: The relationships between XPC polymorphisms (Lys939Gln and Ala499Val) and the susceptibility to colorectal cancer (CRC) have been studied by several researchers, but the results were inconclusive. To get a more precise estimation of the relationships, we conducted this meta-analysis. METHODS: A total of 9 case-control studies, including 3679 cases and 33551 controls for Lys939Gln and 1327 cases and 30438 controls for Ala499Val, were selected. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive, dominant and recessive models. RESULTS: When all the studies were pooled into the meta-analysis, no evidence showing a significant association between XPC polymorphisms and CRC risk was noticed. In the subgroup analysis by ethnicity and study design, no significant association was also found. CONCLUSION: In conclusion, this meta-analysis indicated that the XPC polymorphisms were not risk factors for the development of CRC.
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Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Polimorfismo Genético , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: The purpose of this study was to compare short-term clinical outcomes of ileocolonic functional end-to-end anastomosis (FEEA) and end-to-side anastomosis (ESA) following resection of the right colon for cancer. METHODS: We enrolled 379 patients who underwent ileocolonic anastomosis following resection of the right colon for cancer by a single surgeon, from January 2009 through June 2012. Patient characteristics, operative results, and postoperative complications were analyzed. RESULTS: A total of 164 patients received ESA and 215 patients received FEEA. The FEEA group had a lower incidence of anastomotic error (0.9% versus 4.3%; P = 0.04) and a shorter operating time (140.4 ± 14.9 min versus 150.5 ± 20.1 min; P = 0.001). The length of hospital stay (10.9 ± 3.5 days versus 11.3 ± 4.0 days; P = 0.36) and anastomotic leakage (1.8% versus 0.5%; P = 0.20) were similar in both groups. No relevant differences between FEEA and ESA were observed for blood loss, retrieved lymph nodes, first flatus and postoperative complications. CONCLUSION: An FEEA after right hemicolectomy for colon cancer is a safe and reliable anastomotic technique, resulting in a favorable outcome in selected patients with the right colon cancer.
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Anastomose Cirúrgica/efeitos adversos , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Fístula Anastomótica/etiologia , Neoplasias do Colo/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: The extent of lymphadenectomy appropriate for patients with cT2 colorectal cancer (CRC) remains controversial. This study was conducted to compare the survival outcomes of patients with cT2 CRC after D3 or D2 lymph node dissection (LND). PATIENTS AND METHODS: Qualifying subjects (N=590) had undergone radical colorectal resections for cT2 CRC and were grouped according to tumor histological type as either well-differentiated (WDA) or non-well-differentiated (nWDA) adenocarcinoma. Each group was further stratified into D3 or D2 LND according to the extent of lymph node dissection. Propensity score matching (PSM) was applied to balance potential confounding factors, and identify independent prognostic risk factors using Cox regression analysis. Primary outcome measures were overall survival (OS), cancer-specific survival, (CSS) and relapse-free survival rate (RFS). RESULTS: Prior to PSM, OS and CSS differed significantly (p=0.001 and p=0.021, respectively) for D3 and D2 LND subsets in the nWDA group. Estimated hazard ratios (HRs) for OS and CSS were 3 [95% confidence interval (CI)=1.3-6.8; p=0.0084] and 3.2 (95%CI=1-10; p=0.047), respectively, in the D3 LND subset. After matching, significant differences in OS (p=0.007) and CSS (p=0.012) were also observed, with corresponding estimated HRs of 4 (95%CI=1.2-14; p=0.028) and 16 (95%CI=1.2-220; p=0.034). In the WDA group, D2 and D3 LND procedures displayed similar favorable prognoses before and after matching. Postoperative complications emerged as independent risk factors for prognosis in the WDA group of patients with cT2 CRC. CONCLUSION: D3 LND improved survival outcomes in patients with non-well-differentiated cT2 CRC. In patients with well-differentiated cT2 adenocarcinoma, D3 LND was preferred to reduce perioperative complications.
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Adenocarcinoma , Neoplasias Colorretais , Humanos , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo/métodos , Neoplasias Colorretais/patologia , Adenocarcinoma/patologia , Prognóstico , Linfonodos/patologia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: While intracorporeal anastomosis (IA) has been widely used in totally laparoscopic right colectomy, its application in laparoscopic segmental left colectomy for splenic flexure cancer remains underexplored, particularly in large-scale studies with long-term outcomes. This research aims to assess the technical feasibility and oncological efficacy of IA in treating colonic splenic flexure carcinoma, drawing insights from both short-term and long-term outcomes of a retrospective cohort. MATERIALS AND METHODS: A retrospective analysis was conducted on 342 patients diagnosed with colonic splenic flexure carcinoma in three Chinese medical centers. These patients underwent laparoscopic segmental left colectomy between December 2014 and December 2019 across three medical institutions. Comprehensive data encompassing demographics, disease features, pathological characteristics, operative details, and both short-term and long-term outcomes were gathered and scrutinized. Using propensity scores, each patient from the IA cohort was paired with a counterpart from the extracorporeal anastomosis (EA) cohort. RESULTS: IA was performed on 129 patients, while 213 underwent EA. Post-propensity score matching resulted in 129 matched pairs. After matching, many baseline characteristics were balanced. The IA cohort exhibited several advantages, including shorter incision lengths ( P <0.001) and more extensive proximal and distal resection margins ( P =0.003, P <0.001). Additionally, the IA method facilitated a more rapid postoperative recovery as indicated by quicker return of bowel movements (resumption of passing flatus [2.7 (1.0-7.0) days vs. 3.3 (2.0-8.0) days, P <0.001] and defecation [3.7 (1.0-9.0)] days vs. 4.5 (2.0-9.0) days, P <0.001]), faster discharges [6.6 (3.0-15.0) days vs. 8.3 (5.0-20.0) days, P <0.001], and decreased need for rescue analgesics ( P <0.001). The rate of postoperative complications, as rated by the Clavien-Dindo classification, remained consistent across both techniques ( P =0.087). Furthermore, the cosmetic outcome rated by Patient Scar Assessment Questionnaire and Scoring System (PSAQ) was markedly superior in the IA group ( P <0.001). Both approaches demonstrated equivalent 5-year overall (82.7% vs. 82.1%, P =0.419) and disease-free survival (80.9% vs. 78.1%, P =0.476). Subsequent stratification analysis revealed that IA achieved comparable 5-year overall (80.7% vs. 82.0%, P =0.647) and disease-free survival (78.1% vs. 76.4%, P =0.734) in patients with locally advanced colon cancer. CONCLUSION: Employing IA for laparoscopic segmental left colectomy in cases of splenic flexure carcinoma is not only safe but also offers enhanced cosmetic results and expedited postoperative recovery. Oncologically speaking, IA in left segmental colectomy for splenic flexure carcinoma can yield therapeutic outcomes comparable to those of EA, even in patients with locally advanced colon cancer.
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Carcinoma , Colo Transverso , Neoplasias do Colo , Laparoscopia , Neoplasias Esplênicas , Humanos , Colo Transverso/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Neoplasias do Colo/cirurgia , Neoplasias Esplênicas/cirurgia , Colectomia/efeitos adversos , Colectomia/métodos , Anastomose Cirúrgica/métodos , Carcinoma/cirurgiaRESUMO
Colorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different characteristics in immunotherapy. Low sensitivity of diagnostic biomarkers and metastasis are still the principal cause of mortality, especially in MSI. Here, applying computational programs, we identified recurring expression programs based on single cell RNA sequencing (scRNA-Seq) data of CRC cell lines. Notably, three MSI specific recurring modules were identified by non-negative matrix factorization (NMF). High NMF score genes enriched in the function of metabolism and inflammatory response. Focusing on top specific active transcription factor (TF), RUNX3 (Runt-related transcription factor 3), our results suggest that T cell infiltration was increased in RUNX3 high MSI CRC samples. Unbiased Gene Set Enrichment Analysis (GSEA) showed that RUNX3 was strongly associated with immune and metastasis related functions, such as Interferon Gamma (IFN-γ) and EPITHELIAL MESENCHYMAL TRANSITION (EMT). In addition, RUNX3 shows specific highly activated at epigenetic level in MSI compared with other gastrointestinal carcinomas. Positive correlation between RUNX3 and most immune checkpoints further confirmed RUNX3 might have crucial roles in MSI cancer progression and immunotherapy. Taken together, these results indicate significant tumor heterogeneity of two CRC subtypes at single-cell level and epigenetic modification level. These results also linked transcriptional dysregulation with immune infiltration at single-cell level in MSI, which may advance the application of scRNA-Seq technology in immunotherapy and contribute to developing novel biomarkers of this malignancy.
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BACKGROUND/AIM: This study investigated the significance of lymph node metastasis (LNM) in patients with pT2 colorectal cancer (CRC). PATIENTS AND METHODS: This retrospective cohort study was conducted at a high-volume cancer center in Japan and targeted all qualifying patients (n=617) with radically resected pT2 CRC. Subjects were stratified by the presence (LNM+) or absence (LNM-) of LNM to compare cancer-specific survival (CSS) and relapse-free survival (RFS) rates before and after propensity score matching. RESULTS: There were 168 (27.2%) and 449 (72.8%) patients in the LNM+ and LNM- groups, respectively. Tumors in the LNM+ (vs. LNM-) group were more often less differentiated (Poor/Sig/Muc: 26.2% vs. 18.5%; p=0.035); more inclined to lymphatic (45.2% vs. 21.4%; p=0.000), vascular (64.9% vs. 44.8%; p=0.000), or neural (7.7% vs. 3.3%; p=0.019) invasion; and yielded more (≥12) harvested lymph nodes (94.0% vs. 85.5%; p=0.004). Although similar in terms of 5-year CSS (LNM-, 98.7%: LNM+, 95.8%; p=0.117), RFS in the LNM- (vs. LNM+) group was found to be significantly better (95.3% vs. 88.7%; p=0.003). After matching, RFS in the LNM- (vs. LNM+) group remained significantly better (95.4% vs. 88.7%; p=0.027). Recurrence was more likely in the LNM+ (vs. LNM-) group (pre-matching: 13.1% vs. 5.6%, p=0.002; post-matching: 12.4% vs. 5.2%, p=0.027), primarily occurring as liver metastases (pre-matching: 8.3% vs. 1.1%, p=0.002; post-matching: 7.8% vs. 1.3%, p=0.006). CONCLUSION: Lymph node metastasis does not affect CSS after radical resection of pT2 CRC, but vigilance for liver metastasis is essential. Downstaging of T2N+ CRC from stage IIIA to stage IIA is warranted.
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Neoplasias Colorretais , Humanos , Prognóstico , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Linfonodos/patologia , Estadiamento de NeoplasiasRESUMO
BACKGROUND/AIM: The purpose of this study was to elucidate the status and clinical significance of skip lymph node metastasis (LNM) in colorectal cancer. PATIENTS AND METHODS: This is a retrospective cohort study from a high-volume cancer center in Japan. A total of 1,060 patients with primary stage III colorectal cancer (CRC) underwent radical resection were included in the study and divided into skip LNM (LNM) (skip+) and non-skip LNM (skip-) groups. Propensity score matching was used to balance potential confounding factors. The cancer-specific survival (CSS) and relapse-free survival rate (RFS) between the two groups before and after matching were evaluated. RESULTS: Before matching, patients in the skip+ group had a greater number of LNM (pN2: 48.3% vs. 31.1%; p<0.001), more pathological stage IIIC (43.2% vs. 17.6%; p<0.001), and a higher rate of recurrence (38.1% vs. 25.8%; p=0.0045). Consequently, the CSS (p=0.034) and RFS (p=0.005) were worse compared to the skip- group. However, after matching, there were no significant differences in prognosis for CSS (p=0.529) and RFS (p=0.515). In multivariate analysis, skip+ was not an independent risk factor for prognosis. However, the skip+ LNM group was more likely to have local lymph node recurrence. CONCLUSION: Skip+ LNM was more likely to happen in later stage CRCs, leading to significantly poorer survival outcomes. However, when all background factors were matched, the prognosis of the skip+ group was not worse. Surgeons need to be more alert to the possibility of local recurrence in patients with skip LNM.
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Relevância Clínica , Neoplasias Colorretais , Humanos , Metástase Linfática , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia , JapãoRESUMO
Background: There is currently no universally-accepted, ideal method of esophagogastric reconstruction to address reflux esophagitis and anastomotic complications of esophagogastrostomy after proximal gastrectomy. Case Report: In June 2022, two patients with Siewert type II carcinoma of esophagogastric junction underwent laparoscopic proximal gastrectomies, using a novel esophagogastrostomy technique of Conical remnant GastroEsophageal side-Overlap fundoplication (CGEO). On postoperative day 4, upper gastrointestinal fluoroscopy was performed, with patients in downward and left oblique positions, allowing gastrografin to accumulate within fundic reconstructions. No reflux into the esophagus was subsequently observed, and both patients were discharged (postoperative days 9 and 11). Six months after surgery, endoscopic view showed that the reconstructed cardia returned to its normal state, in the absence of any reflux symptoms. As of April 2023, we have operated on four patients using CGEO, and all of them recovered without obvious reflux symptoms. Conclusion: CGEO is a feasible and safe reconstructive esophagogastrostomy procedure following laparoscopic proximal gastrectomy for Siewert type II esophagogastric junction carcinoma.
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Apatinib has been shown to clinically enhance anti-PD-1 immunotherapy for advanced gastric cancer (GC). However, the complexity of GC immunosuppression remains a challenge for precision immunotherapy. Here, we profile the transcriptomes of 34,182 single cells from GC patient-derived xenografts of humanized mouse models treated with vehicle, nivolumab, or nivolumab plus apatinib. Notably, excessive expression of CXCL5 in the CellCycle malignant epithelium, induced by anti-PD-1 immunotherapy and blocked by combined apatinib treatment, is found to be a key driver of tumor-associated neutrophil (TAN) recruitment in the tumor microenvironment through the CXCL5/CXCR2 axis. We further show that the protumor TAN signature is associated with anti-PD-1 immunotherapy-related progressive disease and poor cancer prognosis. Molecular and functional analyses in cell-derived xenograft models confirm the positive in vivo therapeutic effect of targeting the CXCL5/CXCR2 axis during anti-PD-1 immunotherapy. Altogether, our study elucidates the GC immunosuppressive landscape in anti-PD-1 immunotherapy and highlights potential targets for overcoming checkpoint immunotherapy resistance.
Assuntos
Nivolumabe , Neoplasias Gástricas , Animais , Camundongos , Humanos , Nivolumabe/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Ecossistema , Imunoterapia , Imunossupressores/farmacologia , Microambiente TumoralRESUMO
OBJECTIVE: To investigate effect of the treatments and prognostic factors of patients with pulmonary metastasis from colorectal cancer. METHODS: Clinical data of 79 patients who suffered from lung metastatic diseases from colorectal cancer in 1990 - 2010 were retrospectively analyzed. The number of patients who had received lung operation was 22, and non-operated group contained 57 patients. Compared the prognosis of operated group and non-operated group and analyzed the prognostic factors. RESULTS: The median survival time after the pulmonary resections was 34.5 months; the overall survival of 1-, 3- and 5-year survival rates were 90.9%, 45.4% and 4.5%, and the overall of 1-, 3-, and 5-year survival rate in non-operated group were 59.6%, 14.0% and 0. The surgery (RR = 4.805, 95% CI: 1.864 - 12.384, P = 0.001) and the number of metastasis (RR = 2.177, 95% CI: 1.431 - 3.314, P = 0.010) were the factors that could influence the patients prognosis. CONCLUSION: The surgery for pulmonary metastases from colorectal cancer is effective.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To learn more about the impact of college sports services on student sports activity intentions, as well as the function of pleasure and involvement as a mediating factor in this process. According to the nature of the service, this study separates college sports services into basic and advanced sports two types, selects 482 students from five institutions in Hunan Province for a questionnaire survey based on spatial dimensions, and analyzes the data using a structural equation model. The findings show that (1) there is a positive correlation between college students' perception levels of basic and advanced sports services (p = 0.01); (2) perception of basic sports services is closely related to cognize involvement (r = 0.717), and perception of advanced sports services is closely related to affective involvement (r = 0.830); and (3) perception of basic sports services is closely related to cognize involvement (r = 0.717). (3) Satisfaction and involvement show a substantial mediation effect between sports service and sports behavioral intention, with involvement having a bigger influence on sports behavioral intention (effect percent = 52.63%) than satisfaction. (4) Advanced sports services are easier to improve students' behavioral intentions than basic sports services in a comparison of the two categories of college sports services. To summarize the findings of the four studies, it can be seen that ensuring the balanced development of basic and advanced sports services, adjusting service content to increase student involvement, and improving resource allocation to advanced sports service content are all effective ways to strengthen students' sports behavioral intention in the service strategy.