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1.
J Exp Clin Cancer Res ; 43(1): 225, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135122

RESUMO

BACKGROUND: Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to be further elucidated. METHODS: LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. RESULTS: LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop. CONCLUSIONS: The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients.


Assuntos
Antígeno B7-H1 , Antígeno CD47 , Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/imunologia , MicroRNAs/genética , Antígeno CD47/metabolismo , Antígeno CD47/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Animais , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Evasão Tumoral/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Masculino , Feminino , Proliferação de Células , Retroalimentação Fisiológica , Prognóstico , Camundongos Nus
2.
Cancer Manag Res ; 16: 225-243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525373

RESUMO

Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the "CMS classifier" and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting "seed" of tumor cells of different CMS groups had a preference for metastasis to "soil" of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.

3.
Medicine (Baltimore) ; 102(39): e35350, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773815

RESUMO

Abdominal adhesion occurs commonly in clinical practice, causing unfavorable symptoms and readmission. The ileostomy operation is a common surgical procedure and we utilized this model to evaluate abdominal adhesion. Adhesion grade score was calculated in 35 patients (Cohort 1) and subjected to correlation and receiver operating characteristic analysis. Then 98 consecutive patients (Cohort 2) who underwent ileostomy and ileostomy closure were included into a retrospective study. Logistic regression analysis was performed, and the risk of small bowel obstruction was also assessed. The time of ileostomy closure correlated with adhesion grade score in Cohort 1, justifying its use as an indicator of abdominal adhesion. All patients in Cohort 2 were then divided into the high- and low-adhesion group. A multi-variable logistic regression analysis indicated that type of surgery and peritoneum suture during ileostomy were significant factors affecting the risk of abdominal adhesion. Abdominal adhesion had the trend to prolong the length of stay postoperatively without increasing the risk of bowel obstruction. Nine patients suffered bowel obstruction, and age older than 65 significantly increased the risk. We proposed the ileostomy procedure to be a model of abdominal adhesion, and the operative time of ileostomy closure could be used as an alternative of adhesion score. Type of surgery and peritoneum suture may be risk factors of abdominal adhesion. Older age increased the risk of small bowel obstruction after ileostomy surgery.


Assuntos
Anormalidades do Sistema Digestório , Obstrução Intestinal , Humanos , Ileostomia/efeitos adversos , Ileostomia/métodos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Anormalidades do Sistema Digestório/complicações
4.
Front Surg ; 10: 1171382, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576920

RESUMO

Aim: To evaluate the efficacy and safety of simple TaTNE in the treatment of low rectal cancer compared with laparoscopic transabdominal TME. Methods: We collected patients with low rectal cancer admitted to our hospital between January 2019 and November 2021 who received simple TaTME or laparoscopic transabdominal TME. The main outcome was the integrity of the TME specimen. Secondary outcomes were the number of lymph nodes dissected, intraoperative blood loss, operative time, surgical conversion rate, Specimen resection length, circumferential margin (CRM), and distal resection margin (DRM), complication rate. In addition, the Wexner score and LARS score of fecal incontinence were performed in postoperative follow-up. Results: Pathological tissues were successfully resected in all patients. all circumferential margins of the specimen were negative. Specimen resection length was not statistically significant (9.94 ± 2.85 vs. 8.90 ± 2.49, P > 0.05). The incidence of postoperative complications in group A (n = 0) was significantly lower than that in group B (n = 3) (P > 0.05). There was no significant difference in operation time between group A and group B (296 ± 60.36 vs. 305 ± 58.28, P > 0.05). Among the patients with follow-up time less than 1 year, there was no significant difference in Wexner score and LARS score between group A and group B (P > 0.05). However, in patients who were followed up for more than 1 year, the Wexner score in group A (9.25 ± 2.73) was significantly lower than that in group B (17.36 ± 10.95) and was statistically significant (P < 0.05). Conclusion: For radical resection of low rectal cancer, Simple TaTME resection may be as safe and effective as laparoscopic transabdominal TME, and the long-term prognosis may be better.

5.
J Immunother Cancer ; 11(8)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37597850

RESUMO

BACKGROUND: Immunotherapy, including adoptive cell therapy (ACT) and immune checkpoint inhibitors (ICIs), has a limited effect in most patients with colorectal cancer (CRC), and the efficacy is further limited in patients with liver metastasis. Lack of antitumor lymphocyte infiltration could be a major cause, and there remains an urgent need for more potent and safer therapies for CRC. METHODS: In this study, the antitumoral synergism of low molecular weight heparin (LMWH) combined with immunotherapy in the microsatellite stable (MSS) highly aggressive murine model of CRC was fully evaluated. RESULTS: Dual LMWH and ACT objectively mediated the stagnation of tumor growth and inhibition of liver metastasis, neither LMWH nor ACT alone had any antitumoral activity on them. The combination of LMWH and ACT obviously increased the infiltration of intratumor CD8+ T cells, as revealed by multiplex immunohistochemistry, purified CD8+ T-cell transfer assay, and IVIM in vivo imaging. Mechanistically, evaluation of changes in the tumor microenvironment revealed that LMWH improved tumor vascular normalization and facilitated the trafficking of activated CD8+ T cells into tumors. Similarly, LMWH combined with anti-programmed cell death protein 1 (PD-1) therapy provided superior antitumor activity as compared with the single PD-1 blockade in murine CT26 tumor models. CONCLUSIONS: LMWH could enhance ACT and ICIs-based immunotherapy by increasing lymphocyte infiltration into tumors, especially cytotoxic CD8+ T cells. These results indicate that combining LMWH with an immunotherapy strategy presents a promising and safe approach for CRC treatment, especially in MSS tumors.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias Colorretais/tratamento farmacológico , Microambiente Tumoral
6.
BMC Gastroenterol ; 23(1): 270, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550605

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies in the world. This study proposes to reveal prognostic biomarkers for the prognosis and treatment of CRC patients. METHODS: Differential analysis of OSBPL3 was performed in pan-cancer, and the correlation between clinical stage and OSBPL3 was analyzed. Multiple omics analysis was used to compare the relationship between survival of patients and copy number variation, single nucleotide variant, and methylation status. Survival differences between high and low OSBPL3 expression groups were analyzed. Differentially expressed genes (DEGs) between high and low OSBPL3 expression groups were obtained, and functional enrichment analysis was implemented. Correlations between immune cells and OSBPL3 was analyzed. Drug sensitivity between the two OSBPL3 expression groups was compared. Moreover, the expression of OSBPL3 was verified by immunohistochemistry and real-time quantitative PCR. RESULTS: OSBPL3 was differentially expressed in 13 tumors and had some correlations with T and N stages. OSBPL3 expression was regulated by methylation and higher OSBPL3 expression was associated with poorer prognosis in CRC. 128 DEGs were obtained and they were mainly involved in signaling receptor activator activity, aspartate and glutamate metabolism. T cell gamma delta and T cell follicular helper were significantly different in the high and low OSBPL3 expression groups. Moreover, OSBPL3 showed negative correlations with multiple drugs. OSBPL3 was significantly upregulated in CRC samples compared to normal samples. CONCLUSIONS: A comprehensive analysis demonstrated that OSBPL3 had potential prognostic value, and guiding significance for CRC chemotherapeutic.


Assuntos
Neoplasias Colorretais , Multiômica , Humanos , Prognóstico , Variações do Número de Cópias de DNA , Transdução de Sinais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a Ácido Graxo
7.
Water Sci Technol ; 87(10): 2529-2540, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37257107

RESUMO

To solve the problem of imperfect flash flood warning indicators in mountainous watersheds, this study proposes a conversion method of critical rainfall for different warning periods on the basis of the existing stormwater calculation formulae and applies it to typical mountainous watersheds. The specific method is to use the multiplicative power function method to interpolate and extend the early warning indicators of other time periods through the known early warning indicators of some time periods, apply them to Hengmiao Village and Gaolou Village, typical disaster prevention objects in Qufu City, Shandong Province, China, and verify the rationality of the results. The results show that the multiplicative power function method interpolates and extends the early warning indexes of 0.5, 1, 3, 6, 12, and 24 h under the same soil moisture condition. Based on the historical actual mountain flood disaster rainfall, the correlation coefficient R2 and Nash coefficient Ens are calculated to be 0.85 and 0.86, respectively, which verifies the applicability of this method. This study provides a convenient and quick way to unify the time series of regional early warning indicators and a feasible way for other regions to study regional overall early warning.


Assuntos
Desastres , Inundações , Cidades , China , Solo
8.
Water Sci Technol ; 87(4): 892-909, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36853769

RESUMO

Flash flood disaster is one of the important natural disasters, bringing harm to human life and causing serious economic losses, so it is urgent to improve the accuracy of flash flood warning. To determine the critical rainfall and early warning indicators of disaster prevention objects, the Shuyuan Watershed of Qufu City Shandong Province was selected as the research object, the key disaster prevention objects were screened and finally, Hengmiao Village and Gaolou Village were selected as typical disaster prevention objects. Empirical analysis method, Storm analysis method, and model analysis method were used to calculate the critical rainfall at different times under different soil water content conditions, compare and analyze the rationality and existing problems of these three methods, and comprehensively determine the indicators of typical disaster prevention objects under different circumstances. The results show that the value of the index calculated by the storm analysis method is small and calculated by the model analysis method is large. This paper can improve the accuracy of flash flood warning, select the critical rainfall calculation method according to local conditions, accurately calculate the parameter values, and deal with the problem of effective early warning in the region as a whole.


Assuntos
Desastres , Inundações , Humanos , Solo , Água
9.
Am Surg ; 89(4): 1009-1017, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34783266

RESUMO

BACKGROUND: In recent years, intersphincteric resection (ISR) has been increasingly used to replace abdominoperineal resection (APR) in the surgical treatment of ultra-low rectal cancer. AIM: This study was to compare the clinical efficacy of ISR and APR. METHODS: Between 2012 and 2018, 74 consecutive patients with ultra-low rectal cancer underwent ISR or APR in our medical center. A retrospective comparison of these 2 procedures was performed. RESULTS: A total of 43 patients underwent ISR and 31 underwent APR were included in the study. No significant differences were found between 2 groups in gender, age, BMI, and ASA score. Intersphincteric resection group showed shorter operative time (P = .02) and less blood loss (P = .001). Hospital stays, time to soft diet, and postoperative 30-day complications were not significantly different between the 2 groups. R0 resection achieved 100% in both the groups. As for the long-term outcomes, the survival and recurrence rate were similar between 2 groups. Moreover, the LARS and Wexner score showed that the postoperative anal function after ISR were satisfactory. CONCLUSION: This study suggested that ISR was feasible and safe for selected patients with ultra-low rectal cancer, with clinically superior outcomes in select patients (small tumors/further from the anal verge) and similar oncological outcomes to APR, and the anal functional outcomes after ISR were acceptable.


Assuntos
Protectomia , Neoplasias Retais , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Retais/cirurgia , Reto/cirurgia , Protectomia/métodos , Canal Anal/cirurgia , Complicações Pós-Operatórias/epidemiologia
10.
Front Oncol ; 12: 972454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081551

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.

11.
Bioengineering (Basel) ; 9(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35877369

RESUMO

BACKGROUND: Anal sphincter incontinence (ASI) can cause a serious decline in the quality of life and can cause a socioeconomic burden. Studies have shown that bone marrow mesenchymal stem cells (MSC) have significant therapeutic effects on ASI, but the cost and risk of MSC harvest limit their further application. In contrast, adipose tissue derived stem cells (ADSC) and cellular stromal vascular fraction (CSVF) as stem cell sources have multipotency and the advantage of easy harvest. OBJECTIVE: Here we aim to investigate the effects of ADSC and CSVF on treating ASI and compare them to that of bone marrow MSC. METHODS: Bone marrow MSC, ADSC, and CSVF were obtained and labeled with green fluorescent protein (GFP), and CSVF was labeled with DIL. Sprague Dawley (SD) rats were divided into 5 groups. Four groups were injected with 0.2 mL phosphate buffer saline (PBS), 1 × 107/0.2 mL of MSC, ADSC, or CSVF, respectively, after model establishment. The control group received no treatment. The repair was assessed by anal functional tests and immunostaining on day 5 and day 10 after injection. RESULTS: MSC, ADSC, and CSVF significantly promoted tissue repair and the recovery of muscle contraction and electromyographic activity in ASI. The generation of myosatellite cells by injected MSC, ADSC, and CSVF was found in the wounded area. On day 5, CSVF showed highest therapeutic effect, while on day 10, MSC and ADSC showed higher therapeutic effects than CSVF. When comparing the effects of MSC and ADSC, ADSC was slightly better than MSC in the indexes of anal pressure, etc. Conclusion: ADSC and CVSF are alternative stem cell sources for ASI repair.

12.
Mol Ther ; 30(4): 1578-1596, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35033632

RESUMO

N6-methyladenosine (m6A) methylation, which is modified by the METTL3/METTL14 complex, is a dominant internal modification in mammalian RNA and tightly linked to cancer progression. Here we reveal that METTL3-promoted cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) are associated with expression and membrane localization of ß-catenin (encoded by CTNNB1), as opposed to Wnt signaling activation in various types of cancer cells, including cervical, lung, and liver cancer. Specifically, METTL3 regulates the transcription, mRNA decay, translation, and subcellular localization of ß-catenin. For CTNNB1 expression, METTL3 indirectly suppresses CTNNB1 transcription by stabilizing its transcription suppressor E2F1 mRNA; deposition of 5'UTR m6A in CTNNB1 promotes its decay in a content-dependent manner via YTHDF2 recognition; 5'UTR m6A in CTNNB1 suppresses its translation efficiency, whereas the global METTL3 level controls the canonical and non-canonical translation of CTNNB1, which is probably associated with the interaction between YTHDF1 and eIF4E1/eIF4E3. For ß-catenin translocation, METTL3 represses membrane localization of ß-catenin and its interaction with E-cadherin by downregulating c-Met kinase, leading to inhibition of cell motility. In vitro, in vivo, and clinical analyses confirm the essential role of ß-catenin and its expression regulators in cancer cell dissemination. The findings not only expand our understanding of m6A modification and its roles in gene expression and subcellular localization of targets but also suggest that the METTL3/ß-catenin axis might be a potential target to inhibit cancer metastasis.


Assuntos
Neoplasias , beta Catenina , Regiões 5' não Traduzidas , Animais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Mamíferos , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Neoplasias/genética , beta Catenina/genética , beta Catenina/metabolismo
13.
Bioengineering (Basel) ; 10(1)2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36671604

RESUMO

BACKGROUND: The long-term prognosis of current treatments for anal sphincter incontinence (ASI) is poor. Here, we explored the efficacy of tissue adipose stromal vascular fraction SVF (tSVF) on ASI and compared it to that of cellular SVF (cSVF). We then investigated possible mechanisms. METHODS: Rat cSVF and tSVF were isolated and labeled with DIL. One day after modeling, three groups received phosphate-buffered saline (PBS), cSVF, tSVF, respectively. The control group received nil modeling nor any treatments. The effect was assessed by function test for anal pressure and electromyography, and staining for fiber content, proliferation and differentiation at day 5 and day 10. RESULTS: cSVF injection resulted in faster healing than tSVF. The cSVF group showed significant improvement on anal pressure on day 10. For the electromyography test, cSVF showed significant improvement for the frequencies on day 10, and for the peak values on both time points, while tSVF showed significant improvement for the peak values on day 10. The two SVF both alleviated fibrosis. Immunofluorescence tracing identified differentiation of some injected cells towards myosatellite cells and smooth muscle cells in both SVF groups. For all the tests, the tSVF group tends to have similar or lower effects than the cSVF group with no significant difference. CONCLUSION: cSVF and tSVF are both safe and effective in treating ASI, while the effect of cSVF is slighter higher than tSVF.

15.
Gynecol Obstet Invest ; 86(5): 454-459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34689138

RESUMO

OBJECTIVES: Rectocele is common in female patients. To date, there is no literature comparing outcomes of rectocele repairs in combination with other perineal surgeries. We aim to analyze perioperative morbidity and mortality as well as long-term outcome of rectocele repair in combination with other perineal surgeries (RR combination) and compare this with solo rectocele repair (solo RR). DESIGN: The type of study was case-control. Data of patients who received solo rectocele repair or rectocele repair in combination with other perineal surgeries between January 2011 and December 2015 were identified and reviewed in a prospectively maintained and IRB-approved database. Ninety-eight patients were included, including 41 patients in the solo RR group and 57 patients in the RR combination group. The demographics, characteristics of patients, short-term complications, long-term complications, and morbidity of the 2 groups were observed. METHODS: The demographics, characteristics of patients, short-term complications, long-term complications, and morbidity of the 2 groups were compared, respectively. Covariate adjustment was analyzed by multivariate logistic and Cox regression analysis. RESULTS: Ninety-eight patients with a median age of 57 were included, involving 41 patients in the solo RR group and 57 patients in the RR combination group. Other than the operative approach (p < 0.01), demographics and preoperative characteristics of the 2 groups were comparable. All variables, including length of stay, estimated blood loss, self-limiting rectal bleeding, transfusion, urinary retention, rectal stricture, rectal and perineal infection, rectovaginal abscess, reoperation, effective resolution of obstructive defecation symptoms, residual symptoms rate, and recurrence rate, were comparable among the 2 groups except for operative time (p = 0.03). LIMITATIONS: This study is a single-center study, which may cause bias. In addition, the sample size is limited. Staging of rectocele and routine imaging studies were not performed. CONCLUSIONS: Rectocele repair in combination with other perineal surgeries is feasible, and outcomes are comparable with solo rectocele repair. Transanal versus transvaginal repairs appear to have no influence on outcomes.


Assuntos
Retocele , Reto , Biópsia , Constipação Intestinal , Feminino , Humanos , Períneo/cirurgia , Retocele/cirurgia , Resultado do Tratamento
16.
Front Oncol ; 11: 685577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604029

RESUMO

OBJECTIVE: The mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC. METHODS: Flow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher's exact test and non-parametric Wilcoxon's matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC. RESULTS: We found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels. CONCLUSION: The mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.

17.
Cancer Manag Res ; 13: 4777-4790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168497

RESUMO

BACKGROUND: Mucinous adenocarcinoma (MA) is a subtype of colorectal cancer (CRC) associated with a higher incidence of local extension and worse survival compared to non-mucinous adenocarcinoma, but few studies have investigated surgery-related predictors for recurrence of MA. Therefore, we aimed to elucidate the predictors for local recurrence and remote metastasis of MA after surgery. PATIENTS AND METHODS: This study retrospectively analyzed 162 patients with mucinous colorectal adenocarcinoma (MAC) after radical resection. Analysis variables included demographics, clinical indicators, pathologic stage, surgical procedure, adjuvant therapy, and recurrence. Univariate and multivariate analyses were performed to investigate the risk factors for local and distant tumor relapse. RESULTS: A total of 162 patients (86 male) with a mean age of 58.26 years were included; 70.37% of patients had colonic tumors, and 29.63% had rectal tumors. The 5-year disease-free survival (DFS) rates for these patients were as follows: 100% for TNM stage I, 71.2% for stage II, and 47.8% for stage III. Five-year DFS rates of MAC, colonic and rectal MA were 62.0%, 65.8%, and 51.7%, respectively. Local recurrence occurred in 38 patients and distant metastasis in 33 patients. In univariate analysis, predictors for local recurrence of MAC were intraoperative blood loss, intraoperative transfusion, and N2 stage; and predictors for distant metastasis were male sex, CA199, CEA, intraoperative blood loss, T4 stage, and N2 stage. In multivariate analysis, predictors for local recurrence of MAC were intraoperative transfusion (P=0.04, OR=4.175) and N2 stage (P=0.000, OR=5.291), and predictors for distant metastasis were male sex (P=0.049, OR=2.410), CA199 (P=0.02, OR=1.003), and T4 stage (P=0.007, OR=4.006). CONCLUSION: Intraoperative transfusion and N2 stage were significant predictors for local recurrence. Male sex, CA199, and T4 stage were significant predictors for distant metastasis. Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to treatment and follow-up of MAC.

18.
Future Oncol ; 17(10): 1185-1195, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33289395

RESUMO

Aims: To addresses whether surgical procedure (proximal gastrectomy [PG] vs total gastrectomy [TG]) influences survival outcomes. Methods: Patients were selected from Surveillance, Epidemiology and End Results Program (SEER) database. Survival curve was used to evaluate the differences in overall survival (OS) and cancer-specific survival (CSS). Results: No significant difference was detected in OS and CSS time between PG and TG groups. Also, no significant differences were observed in OS and CSS times between the two groups with respect to clinical stage, tumor stage, node stage, age, gender and tumor differentiation. Tumor differentiation, tumor size, tumor stage, node stage and age were independent prognostic factors in patients with proximal gastric cancer. Conclusions: TG was not necessary for proximal gastric cancer patients, and PG may be considered as an ideal surgery approach.


Assuntos
Gastrectomia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia , Gerenciamento Clínico , Feminino , Gastrectomia/métodos , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Prognóstico , Programa de SEER , Neoplasias Gástricas/patologia , Resultado do Tratamento
19.
J Laparoendosc Adv Surg Tech A ; 31(6): 638-647, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33151807

RESUMO

Background: Mucinous colorectal adenocarcinoma (MAC) has a higher incidence of local extension, leading to lower overall resection rates. Few studies have investigated the outcomes of laparoscopic surgery for MACs to date. Therefore, we aimed to elucidate the validity of laparoscopic surgery for mucinous adenocarcinoma (MAC). Methods: This study analyzed short-term and long-term outcomes between laparoscopic and open surgery for MACs from 2008 to 2018. Multivariate analyses were used to define prognostic factors of overall survival (OS) and disease-free survival (DFS). Results: Patients in the laparoscopy (LAP) group had significantly less blood loss, fewer days to first flatus and to diet, and shorter length of hospital stay. The 3-year and 5-year DFS rates for all stages combined were 65.7% and 62.5% in the LAP group compared with 60.5% and 57.6% in the open (OPEN) surgery group (P = .521). The 3-year and 5-year OS rates for all stages combined were 72.3% and 67.3% in the LAP group compared with 72.6% and 67.8% in the OPEN group (P = .934). OS and DFS in stage II, stage III, and pathological T4 (pT4) stage patients who underwent laparoscopic surgery did not differ from patients who underwent open surgery. Multivariate analysis showed that stage pT4, pN2, and carcinoembryonic antigen (CEA) were significant predictors of OS. Independent factors, including intraoperative blood transfusion, stage pT4, pN2, CEA, and CA19-9, carbohydrate antigen 19-9, have a great effect on DFS. Conclusions: Laparoscopic surgery is a safe and feasible option for mucinous colorectal AC, which provides faster postoperative recovery and less intraoperative blood loss.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Neoplasias Colorretais/cirurgia , Laparoscopia , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/secundário , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Trato Gastrointestinal/fisiopatologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recuperação de Função Fisiológica , Taxa de Sobrevida , Resultado do Tratamento
20.
Surg Innov ; 27(4): 392-401, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32390544

RESUMO

Background. Abdominoperineal resection (APR) has been the standard surgery for ultra-low rectal cancer for a century. In recent years, intersphincteric resection (ISR) has been increasingly used to avoid the permanent colostomy. Up to now, there is no relevant meta-analysis comparing the clinical efficacy of ISR and APR. This meta-analysis aimed to compare the outcomes of these 2 procedures. Methods. A comprehensive search of online databases was performed on PubMed, EMBASE, and the Cochrane Library to obtain comparative studies of ISR and APR. Then the data from studies that met the inclusion criteria were extracted and analyzed. Results. A total of 12 studies covering 2438 patients were included. No significant differences were found between ISR and APR in gender, body mass index, distance from tumor to anal edge, operative time, and blood loss. In addition, hospital stay (weighted mean differences = -2.98 days; 95% confidence interval [CI] = -3.54 to -2.43; P < .00001) and postoperative morbidity (odds ratio [OR] = 0.76; 95% CI = 0.59 to 0.99; P = .04) were significantly lower in ISR group compared with APR group. However, patients who underwent ISR showed lower pathological T-stage (T3T4%, OR = 0.49; 95% CI = 0.28 to 0.86; P = .01) and lymph node metastasis rate (OR = 0.77; 95% CI = 0.59 to 1.01; P = .06) compared with those who underwent APR. Moreover, oncological outcomes were similar between the 2 groups. Conclusion. ISR may provide a safe alternative to APR, with shorter hospital stays, lower postoperative morbidity, and similar oncological outcomes. Well-designed randomized controlled trials are needed to confirm and update the findings of this analysis.


Assuntos
Protectomia , Neoplasias Retais , Canal Anal/cirurgia , Humanos , Duração da Cirurgia , Protectomia/efeitos adversos , Neoplasias Retais/cirurgia , Resultado do Tratamento
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