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1.
Artigo em Inglês | MEDLINE | ID: mdl-38774472

RESUMO

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor. Some papers have reported that colonoscopy could be used to treat PEComa with a predominantly pedunculated polyp, whereas surgical intervention is often required for cases with submucosal-type tumors. These findings suggest that the morphology of PEComa changes dramatically with disease progression. Because of the rapid progression of PEComa, endoscopic treatment remains challenging, and early-stage PEComa morphology is not well understood. A 64-year-old man presented to our hospital for a follow-up colonoscopy after undergoing multiple polypectomies. He had a medical history of colorectal adenoma and prostate cancer. A 4-mm pale blue elevated but not pedunculated lesion was observed in the transverse colon, an area where he had not had polyps previously. Since no epithelial change was observed, the presence of a submucosal tumor, such as a gastrointestinal stromal tumor, was suspected. Cold snare polypectomy was performed, and the lesion was completely resected. Histological evaluation using hematoxylin and eosin staining identified that the submucosal tumor included thickened vascular walls and adipose tissue. Although fragmented due to significant degeneration, spindle-shaped cells staining positive for smooth muscle actin were observed within and surrounding the unstructured hyalinized tissue with calcifications. Based on these findings, the lesion was diagnosed as angiomyolipoma, a subtype of PEComa. Complete resection was confirmed by histopathology. To our knowledge, this PEComa is the smallest of any PEComa reported in the literature. Our finding provides valuable insights into the very early stage of colorectal PEComas.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38770399

RESUMO

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

3.
Cancer Med ; 13(15): e70043, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39087856

RESUMO

BACKGROUND: Recent research indicates a positive correlation between DEP structural domain-containing 1B (DEPDC1B) and the cell cycle in various tumors. However, the role of DEPDC1B in the infiltration of the tumor immune microenvironment (TIME) remains unexplored. METHODS: We analyzed the differential expression and prognostic significance of DEPDC1B in colon adenocarcinoma (COAD) using the R package "limma" and the Gene Expression Profiling Interactive Analysis (GEPIA) website. Gene set enrichment analysis (GSEA) was employed to investigate the functions and interactions of DEPDC1B expression in COAD. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were utilized to assess the proliferative function of DEPDC1B. Correlations between DEPDC1B expression and tumor-infiltrating immune cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) status were examined using Spearman correlation analysis and CIBERSORT. RESULTS: DEPDC1B was highly expressed in COAD. Elevated DEPDC1B expression was associated with lower epithelial-to-mesenchymal transition (EMT) and TNM stages, leading to a favorable prognosis. DEPDC1B mRNA was prominently expressed in COAD cell lines. CCK-8 and colony formation assays demonstrated that DEPDC1B inhibited the proliferation of COAD cells. Analysis using the CIBERSORT database and Spearman correlation revealed that DEPDC1B correlated with four types of tumor-infiltrating immune cells. Furthermore, high DEPDC1B expression was linked to the expression of PD-L1, CTLA4, SIGLEC15, PD-L2, TMB, and MSI-H. High DEPDC1B expression also indicated responsiveness to anti-PD-L1 immunotherapy. CONCLUSIONS: DEPDC1B inhibits the proliferation of COAD cells and positively regulates the cell cycle, showing a positive correlation with CCNB1 and PBK expression. DEPDC1B expression in COAD is associated with tumor-infiltrating immune cells, immune checkpoints, TMB, and MSI-H in the tumor immune microenvironment. This suggests that DEPDC1B may serve as a novel prognostic marker and a potential target for immunotherapy in COAD.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Proteínas Ativadoras de GTPase , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Prognóstico , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/imunologia , Genes Supressores de Tumor , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Instabilidade de Microssatélites , Masculino , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Ciclina B1/genética , Ciclina B1/metabolismo , Feminino
4.
AME Case Rep ; 8: 61, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091544

RESUMO

Background: Adult intussusception is a rare condition that is often associated with a high incidence of malignancy. The optimal management strategy remains controversial, particularly regarding the necessity for bowel reduction before resection. To date, there is a paucity of data on adult intussusception in the English literature. We present two cases of sigmoid colon cancer with intussusception prolapsing through the anus and highlight the different surgical approaches. Case Description: Case 1: an 84-year-old woman presented with sigmoid colon prolapse and biopsy-confirmed adenocarcinoma. Urgent surgery revealed intussusception. Despite unsuccessful manual reduction, the Hutchinson technique successfully resolved the intussusception. Resection with a temporary colostomy was performed. Histopathological examination revealed mucinous adenocarcinoma without metastasis; the patient recovered well. Case 2: a 76-year-old woman with sigmoid colon prolapse presented with abdominal pain and blood-streaked stools. Emergency surgery was performed because of failed reduction attempts and persistent symptoms. Intussusception resolution was achieved through transanal insertion of a circular sizer. Resection with temporary colostomy was performed, after which tubular adenocarcinoma was identified. The patient remains symptom-free 3 years post-surgery. Conclusions: Choice of the surgical approach depends on the ease of intussusception reduction. In cases wherein reduction is straightforward, routine preoperative examinations are preferred given the low risk of injury or cancer cell dissemination. Conversely, in situations such as ours, gentle reduction under general anesthesia might be crucial. In addition, laparoscopic surgery could be beneficial. Importantly, accumulation of reports on adult intussusception could contribute to the standardization of this approach.

5.
Front Oncol ; 14: 1384499, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091906

RESUMO

The oncolytic virus represents a promising therapeutic strategy involving the targeted replication of viruses to eliminate cancer cells, while preserving healthy ones. Despite ongoing clinical trials, this approach encounters significant challenges. This study delves into the interaction between an oncolytic virus and extracellular matrix mimics (ECM mimics). A three-dimensional colorectal cancer model, enriched with ECM mimics through bioprinting, was subjected to infection by an oncolytic virus derived from the vaccinia virus (oVV). The investigation revealed prolonged expression and sustained oVV production. However, the absence of a significant antitumor effect suggested that the virus's progression toward non-infected tumoral clusters was hindered by the ECM mimics. Effective elimination of tumoral cells was achieved by introducing an oVV expressing FCU1 (an enzyme converting the prodrug 5-FC into the chemotherapeutic compound 5-FU) alongside 5-FC. Notably, this efficacy was absent when using a non-replicative vaccinia virus expressing FCU1. Our findings underscore then the crucial role of oVV proliferation in a complex ECM mimics. Its proliferation facilitates payload expression and generates a bystander effect to eradicate tumors. Additionally, this study emphasizes the utility of 3D bioprinting for assessing ECM mimics impact on oVV and demonstrates how enhancing oVV capabilities allows overcoming these barriers. This showcases the potential of 3D bioprinting technology in designing purpose-fit models for such investigations.

6.
Int J Surg Pathol ; : 10668969241265017, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39094576

RESUMO

Aim. Although it is now accepted in the literature that tumour budding (TB) is a useful survival indicator in colon cancer (CC), there are still uncertainties about daily use. Here we methodologically examined the role of TB on survival in CC. Methods. In our study, we examined colon cancer patients who had surgery up to 15 years before presentation. TB was calculated separately using different comprehensive methodological methods. Results. We first investigated an optimal evaluation method. Relationship with prognostic factors was better (Venous invasion [p = .001], advanced pT [p = .003], perineural invasion [p = .040], MSS [p = .016], advanced size [p = .001], tumour obstruction [p = .005], margin involvement [p = .043], and nodal involvement [p = .028]) in Method-1. Similarly, with the same method, the success of the cut-off value, the correlation of TB data (r = .724), and the repeatability of the method (Κappa = .53-.75) were quite good (ROC = .816 [.707-.925]). Then, survival analysis was performed using the best three methods, including this method. In univariate analysis using Method-1, survival analyses were worse in high TB patients (RFS: 81%, p < .001; OS: 84%, p < .001). Multivariate analyses using the same method confirmed that high TB for RFS and OS was an independent poor prognostic parameter for survival (p = .002, Hazard ratio [HR]: 1.42 [1.13-1.80]) and OS (p = .014, HR: 1.38 [1.07-1.79]). Conclusions. With our study, we showed that tumour budding calculated by the standard method is a very valuable prognostic parameter in stage II CC and can contribute to the detection of patients with poor prognosis in stage II CC.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39090330

RESUMO

BACKGROUND: Endoscopic sub-mucosal dissection (ESD) is an established endoscopic modality for the management of colorectal polyps. However, there are no studies regarding the outcomes of ESD from India. In this study, we aimed at evaluating the outcomes of ESD in patients with adenomatous polyps in the colon and rectum. METHODS: Data of consecutive patients who underwent ESD for colorectal polyps from 2018 to 2021 were analyzed, retrospectively. The primary outcome of the study was the technical success of ESD. The secondary outcomes included the rate of histologically complete resection (R0), adverse events and recurrence. RESULTS: Seventy patients (63.5 years, 60% males) underwent ESD for polyps in colon and rectum. A majority were located in rectum (80%) and sigmoid colon (15.7%). Narrow band classification of the polyps was Japanese Narrow Band Imaging Expert Team (JNET)-2a in 50 (71.4%) and JNET-2b in 13 (18.6%) patients. ESD was technically successful in 64 (91.4%) patients using conventional technique (72.8%) and pocket or tunnelling technique (18.6%). There were no major adverse events. Histologically RO was achieved in 58 (82.8%) patients and deep sub-mucosal invasion was noted in 12 patients. At a median follow-up of 19 (interquartile range [IQR] 15-27) months, recurrence was noticed in four (5.7%) patients all of which could be managed endoscopically. CONCLUSION: ESD, performed at a tertiary care centre in India, yields high rates of technical success and histologically R0, with a relatively low incidence of adverse events and recurrences.

9.
Rep Biochem Mol Biol ; 12(4): 586-595, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39086588

RESUMO

Background: Pancreatic cancer and colon cancer pose significant challenges in treatment, with poor prognoses. Natural products have long been explored for their potential as anticancer agents. Iso-mukaadial acetate has shown promise in inducing apoptosis in breast and ovarian cancer cells. The objective of this study was to investigate the effect of Iso-mukaadial acetate on pancreatic (MIA-PACA2) and colon (HT29) cancer cell lines. Methods: Pancreatic (MIA-PACA2) cancer cells, colon (HT29) cancer cells, normal embryonic kidney cells (HEK 293), and normal lung cells (MRC5) were cultured and treated with Iso-mukaadial acetate (IMA) for 24 hours. The viability assays were conducted using Alamarblue reagent and a real-time cell viability monitoring system, xCELLigence. The IC50 values were determined, followed by assessments of ATP production, caspase 3/7 activation, mitochondrial function, morphological changes using a light microscope, and gene expression changes via RT-PCR. Results: This study indicates that Iso-mukaadial acetate exhibited concentration-dependent cytotoxic effects, slowing cellular proliferation in both cancer cell lines. Activation of the mitochondrial apoptotic pathway and caspase 3/7 suggests induction of apoptosis. Reduced ATP production and altered gene expression further support its anticancer properties. Morphological changes after treatment with Iso-mukaadial acetate showed apoptotic characteristics which may suggest that apoptosis was induced. Conclusions: According to the results obtained, Iso-mukaadial acetate shows potential as an anticancer agent, evidenced by its effects on cellular viability, mitochondrial function, ATP production, caspase activation, and gene expression in pancreatic and colon cancer cells. These findings highlight its promise for further investigation and potential in the development of therapeutic agents.

10.
J Anus Rectum Colon ; 8(3): 195-203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086875

RESUMO

Objectives: To clarify whether self-expandable metallic stent (SEMS) placement for obstructive colorectal cancer (CRC) increases perineural invasion (PNI), thereby worsening the prognosis. Methods: In total, 1022 patients with pathological T3 or T4 colon or rectosigmoid cancer who underwent resection were retrospectively reviewed. The study patients were divided into a no obstruction group (n=693), obstruction without stent group (n=251), and obstruction with stent group (n=78), and factors demonstrating an independent association with PNI, the difference in PNI incidence and severity between groups, and the association between PNI and the duration from SEMS placement to surgery were investigated. Survival analysis was performed for each group. Results: On multivariate analysis, SEMS placement (hazard ratio [HR]: 2.08) was independently associated with PNI whereas SEMS placement was not. PNI occurred in 39%, 45%, and 68% of the no obstruction, obstruction without stent, and obstruction with stent group, respectively. In the obstruction with stent group, the proportion of PNI was not associated with the duration from SEMS placement to surgery. Extramural PNI, an advanced form of PNI, demonstrated no increase with increasing interval. The five-year OS was 86.3%, 76.7%, and 73.1% in no obstruction, obstruction without stent, and obstruction with stent group, respectively. On multivariate analysis, obstruction was an independent risk factor of decreased OS (HR: 1.57) whereas SEMS placement was not. Conclusions: The prognosis was comparable between patients with SEMS placement and those with an obstruction who did not undergo SEMS placement, thus demonstrating that SEMS is a viable, therapeutic option for BTS.

11.
Surg Obes Relat Dis ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-39097472

RESUMO

BACKGROUND: Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU). METHODS: PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee. RESULTS: Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures. CONCLUSIONS: This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB.

12.
World J Clin Cases ; 12(22): 5196-5207, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39109028

RESUMO

BACKGROUND: Plasma cell myeloma (PCM) is characterized by hypercalcemia, renal impairment, anemia, and bone destruction. While pleural effusion, ascites, abdominal pain, and bloody stool are common manifestations of lung disease or gastrointestinal disorders, they are rarely observed in patients with PCM. CASE SUMMARY: A 66-year-old woman presented with complaints of recurrent chest tightness, wheezing, and abdominal bloating accompanied by bloody stools. Computed tomography revealed pleural effusion and ascites. Pleural effusion tests showed inflammation, but the T-cell spot test and carcinoembryonic antigen were negative. Endoscopy showed colonic mucosal edema with ulcer formation and local intestinal lumen stenosis. Echocardiography revealed enlarged atria and reduced left ventricular systolic function. The diagnosis remained unclear. Further testing revealed elevated blood light chain lambda and urine immunoglobulin levels. Blood immunofixation electrophoresis was positive for immunoglobulin G lambda type. Smear cytology of the bone marrow showed a high proportion of plasma cells, accounting for about 4.5%. Histopathological examination of the bone marrow suggested PCM. Flow cytometry showed abnormal plasma cells with strong expression of CD38, CD138, cLambda, CD28, CD200, and CD117. Fluorescence in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification, but cytogenetic testing showed no clonal abnormalities. Colonic mucosa and bone marrow biopsy tissues were negative for Highman Congo red staining. The patient was finally diagnosed with PCM. CONCLUSION: A diagnosis of PCM should be considered in older patients with pleural effusion, ascites, and multi-organ injury.

13.
Front Bioeng Biotechnol ; 12: 1439883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104624

RESUMO

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100 nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

14.
Sci China Life Sci ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39110401

RESUMO

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3' splice site (ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3' ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target.

15.
Discov Oncol ; 15(1): 332, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095620

RESUMO

PURPOSE: This study aimed to elucidate the predictive role of an oxidative stress-related genes (OSRGs) model in colon cancer. MATERIALS AND METHODS: First, OSRGs that were differentially expressed between tumor and normal tissues were identified using The Cancer Genome Atlas (TCGA)-(Colorectal Adenocarcinoma) COAD dataset. Then, Lasso COX regression was performed to develop an optimal prognostic model patients were stratified into high- and low-risk groups based on the expression patterns of these genes. The model's validity was confirmed through Kaplan-Meier survival curves and receiver operating characteristic curve (ROC) analysis. Additionally, enrichment analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to uncover underlying mechanisms. RESULTS: A totally of 115 differentially expressed OSRGs were identified within the TCGA cohort, with 17 significantly linked to overall survival. These 17 genes were used to formulate a prognostic model that differentiated patients into distinct risk groups, with the high-risk group demonstrating a notably inferior overall survival rate. The risk score, when integrated with clinical and pathological data, emerged as an independent prognostic indicator of colon cancer. Further analyses revealed that the disparity in prognostic outcomes between risk groups could be attributed to the reactive oxygen species pathway and the p53 signaling pathway. CONCLUSION: A new prediction model was established based on OSRGs. CYP19A1, NOL3 and UCN were found to be highly expressed in tumor tissues and substantial clinical predictive significance. These findings offer new insights into the role of oxidative stress in colon cancer.

16.
J Pathol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092716

RESUMO

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell-T-cell interactions at single-cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: p = 0.07; validation cohort: p = 0.19). We next utilised our region-based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (discovery cohort: p = 0.01; validation cohort: p = 0.003). © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

17.
Cancer Med ; 13(15): e6999, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39096087

RESUMO

INTRODUCTION: People with low income have worse outcomes throughout the cancer care continuum; however, little is known about income and the diagnostic interval. We described diagnostic pathways by neighborhood income and investigated the association between income and the diagnostic interval. METHODS: This was a retrospective cohort study of colon cancer patients diagnosed 2007-2019 in Ontario using routinely collected data. The diagnostic interval was defined as the number of days from the first colon cancer encounter to diagnosis. Asymptomatic pathways were defined as first encounter with a colonoscopy or guaiac fecal occult blood test not occurring in the emergency department and were examined separately from symptomatic pathways. Quantile regression was used to determine the association between neighborhood income quintile and the conditional 50th and 90th percentile diagnostic interval controlling for age, sex, rural residence, and year of diagnosis. RESULTS: A total of 64,303 colon cancer patients were included. Patients residing in the lowest income neighborhoods were more likely to be diagnosed through symptomatic pathways and in the emergency department. Living in low-income neighborhoods was associated with longer 50th and 90th-percentile symptomatic diagnostic intervals compared to patients living in the highest income neighborhoods. For example, the 90th percentile diagnostic interval was 15 days (95% CI 6-23) longer in patients living in the lowest income neighborhoods compared to the highest. CONCLUSION: These findings reveal income inequities during the diagnostic phase of colon cancer. Future work should determine pathways to reducing inequalities along the diagnostic interval and evaluate screening and diagnostic assessment programs from an equity perspective.


Assuntos
Neoplasias do Colo , Renda , Humanos , Feminino , Masculino , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/epidemiologia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Renda/estatística & dados numéricos , Ontário/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Fatores de Tempo , Colonoscopia/estatística & dados numéricos , Colonoscopia/economia , Sangue Oculto , Idoso de 80 Anos ou mais , Características de Residência , Adulto
18.
Cureus ; 16(7): e63821, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39100032

RESUMO

Backgrounds Colorectal surgeons worldwide have differing opinions on the best way to handle rare cases of splenic flexure colon cancers (SFCs). Although the majority of reviews indicate no significant variation in oncological outcomes among the three different procedure types used to treat SFCs, surgeons still exhibit diversity in their practices. This study determined the treatment preferences of colorectal surgeons in Saudi Arabia. Methods A descriptive cross-sectional study evaluated the management of colorectal surgeons in handling SFC cases. We utilized a validated questionnaire developed by Manceau et al., consisting of 14 questions. Emails and phone numbers of members of the Saudi Society of Colorectal Surgery (SSCRS) were gathered. Google Forms surveys were administered from October 1-30, 2023. Results A response rate of 66% (58/88) was obtained among questioned colorectal surgeons. Their responses revealed that there was no consensus regarding the preferred procedure to treat SFCs. The most common treatment reported was segmental colectomy (SC) 21/58 (36.2%), followed by subtotal colectomy (STC) (19/58, 32.8%) and left hemicolectomy (LHC) (18/58, 31%). There was a strong consensus of 96% (56/58) of the respondents in favor of using stapler anastomosis rather than hand sewing. The frequency of performing SC, STC, and LHC in France was 70%, 13%, and 17%, respectively, compared to 36.2%, 32.8%, and 31% in Saudi Arabia, with a p-value of 0.001. The surgeons' preferred approaches to managing SFCs utilizing laparoscopic, open, or hand-aided in France versus Saudi Arabia were 63%, 31%, and 11%, respectively, compared to 84.5%, 8.6%, and 6.9%, with a p-value of 0.001. Conclusion A significant disparity exists regarding the treatment of SFCs between colorectal surgeons in France and Saudi Arabia. Furthermore, there is a lack of consensus among colorectal surgeons in Saudi Arabia regarding the surgical management of SFCs. Hence, it is imperative for the SCRSS to assemble a panel of experts to reach a consensus for the most appropriate and effective treatment of SFCs.

19.
Surg Open Sci ; 20: 156-168, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39100384

RESUMO

The implementation of screening colonoscopy with polyp removal has significantly decreased mortality rates associated with colorectal cancer (CRC), although it remains a major cause of cancer-related deaths globally. CRC typically originates from adenomatous polyps, and increased removal of these growths has led to reduced CRC incidence and mortality. Endoscopic polypectomy techniques, including hot and cold snare polypectomy, play a pivotal role in this process. While both methods are effective for small polyps (<10 mm), recent evidence favors cold snare polypectomy due to its superior safety profile and comparable complete resection rates. Large polyps (>10 mm), particularly those with advanced features, pose increased cancer risks and often require meticulous assessment and advanced endoscopic techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), for resection. This chapter also provides a practical overview of endoscopic techniques for managing colonic obstructions and pericolonic fluid collections, detailing their indications, advantages, disadvantages, and complications. The goal is to improve understanding and application in clinical practice. Additionally, we provide a summary of endoscopic closure techniques that have revolutionized the management of perforations and fistulas, offering safe and effective alternatives to surgery.

20.
Heliyon ; 10(14): e33794, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100449

RESUMO

Aim: To build a ferroptosis-related prognostic model for patients with colon adenocarcinoma (COAD). Methods: COAD expression profiles from The Cancer Genome Atlas were used as the training set and GSE39582 from Gene Expression Omnibus as the validation set. Differentially expressed ferroptosis-related genes between patients with COAD and normal controls were screened, followed by tumor subtype exploration based on ferroptosis-related gene expression levels. A ferroptosis score (FS) model was constructed using least absolute shrinkage and selection operator penalized Cox analysis. Based on FS, patients were subgrouped into high- and low-risk subgroups and overall survival was predicted. The potential prognostic value of the FS model and the clinical characteristics were investigated using receiver operating characteristic curves. Results: Twenty-four differentially expressed ferroptosis-related genes were identified, four of which (CYBB, PRNP, ACSL4, and ACSL6) were included in the prognostic signature. Moreover, age, pathological T stage, and tumor recurrence were independent prognostic factors for COAD. The FS model combined with three independent prognostic factors showed the best prognostic value (The Cancer Genome Atlas: area under the curve = 0.897; GSE39582: area under the curve = 0.858). Conclusion: The novel prognostic model for patients with COAD constructed by pairing the FS model with three important independent prognostic factors showed promising clinical predictive value.

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