RESUMO
A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.
Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor de Morte Celular Programada 1/genética , Adenoma/imunologia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Variações do Número de Cópias de DNA/genética , Feminino , Deriva Genética , Genoma Humano/genética , Humanos , Imunidade/genética , Imunidade/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Intervalo Livre de Progressão , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
OBJECTIVES: Computer-aided characterization (CADx) may be used to implement optical biopsy strategies into colonoscopy practice; however, its impact on endoscopic diagnosis remains unknown. We aimed to evaluate the additional diagnostic value of CADx when used by endoscopists for assessing colorectal polyps. METHODS: This was a single-center, multicase, multireader, image-reading study using randomly extracted images of pathologically confirmed polyps resected between July 2021 and January 2022. Approved CADx that could predict two-tier classification (neoplastic or nonneoplastic) by analyzing narrow-band images of the polyps was used to obtain a CADx diagnosis. Participating endoscopists determined if the polyps were neoplastic or not and noted their confidence level using a computer-based, image-reading test. The test was conducted twice with a 4-week interval: the first test was conducted without CADx prediction and the second test with CADx prediction. Diagnostic performances for neoplasms were calculated using the pathological diagnosis as reference and performances with and without CADx prediction were compared. RESULTS: Five hundred polyps were randomly extracted from 385 patients and diagnosed by 14 endoscopists (including seven experts). The sensitivity for neoplasia was significantly improved by referring to CADx (89.4% vs. 95.6%). CADx also had incremental effects on the negative predictive value (69.3% vs. 84.3%), overall accuracy (87.2% vs. 91.8%), and high-confidence diagnosis rate (77.4% vs. 85.8%). However, there was no significant difference in specificity (80.1% vs. 78.9%). CONCLUSIONS: Computer-aided characterization has added diagnostic value for differentiating colorectal neoplasms and may improve the high-confidence diagnosis rate.
Assuntos
Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Valor Preditivo dos Testes , Computadores , Imagem de Banda Estreita/métodosRESUMO
OBJECTIVES: Lymph node metastasis (LNM) prediction for T1 colorectal cancer (CRC) is critical for determining the need for surgery after endoscopic resection because LNM occurs in 10%. We aimed to develop a novel artificial intelligence (AI) system using whole slide images (WSIs) to predict LNM. METHODS: We conducted a retrospective single center study. To train and test the AI model, we included LNM status-confirmed T1 and T2 CRC between April 2001 and October 2021. These lesions were divided into two cohorts: training (T1 and T2) and testing (T1). WSIs were cropped into small patches and clustered by unsupervised K-means. The percentage of patches belonging to each cluster was calculated from each WSI. Each cluster's percentage, sex, and tumor location were extracted and learned using the random forest algorithm. We calculated the areas under the receiver operating characteristic curves (AUCs) to identify the LNM and the rate of over-surgery of the AI model and the guidelines. RESULTS: The training cohort contained 217 T1 and 268 T2 CRCs, while 100 T1 cases (LNM-positivity 15%) were the test cohort. The AUC of the AI system for the test cohort was 0.74 (95% confidence interval [CI] 0.58-0.86), and 0.52 (95% CI 0.50-0.55) using the guidelines criteria (P = 0.0028). This AI model could reduce the 21% of over-surgery compared to the guidelines. CONCLUSION: We developed a pathologist-independent predictive model for LNM in T1 CRC using WSI for determination of the need for surgery after endoscopic resection. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000046992, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053590).
Assuntos
Inteligência Artificial , Neoplasias Colorretais , Humanos , Metástase Linfática/patologia , Estudos Retrospectivos , Endoscopia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Linfonodos/patologiaRESUMO
BACKGROUND AND AIMS: Because of a lack of reliable preoperative prediction of lymph node involvement in early-stage T2 colorectal cancer (CRC), surgical resection is the current standard treatment. This leads to overtreatment because only 25% of T2 CRC patients turn out to have lymph node metastasis (LNM). We assessed a novel artificial intelligence (AI) system to predict LNM in T2 CRC to ascertain patients who can be safely treated with less-invasive endoscopic resection such as endoscopic full-thickness resection and do not need surgery. METHODS: We included 511 consecutive patients who had surgical resection with T2 CRC from 2001 to 2016; 411 patients (2001-2014) were used as a training set for the random forest-based AI prediction tool, and 100 patients (2014-2016) were used to validate the AI tool performance. The AI algorithm included 8 clinicopathologic variables (patient age and sex, tumor size and location, lymphatic invasion, vascular invasion, histologic differentiation, and serum carcinoembryonic antigen level) and predicted the likelihood of LNM by receiver-operating characteristics using area under the curve (AUC) estimates. RESULTS: Rates of LNM in the training and validation datasets were 26% (106/411) and 28% (28/100), respectively. The AUC of the AI algorithm for the validation cohort was .93. With 96% sensitivity (95% confidence interval, 90%-99%), specificity was 88% (95% confidence interval, 80%-94%). In this case, 64% of patients could avoid surgery, whereas 1.6% of patients with LNM would lose a chance to receive surgery. CONCLUSIONS: Our proposed AI prediction model has a potential to reduce unnecessary surgery for patients with T2 CRC with very little risk. (Clinical trial registration number: UMIN 000038257.).
Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Inteligência Artificial , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Estudos RetrospectivosRESUMO
BACKGROUND AND AIM: Although patients report either improved or worsened halitosis after Helicobacter pylori eradication therapy, such complaints are subjective. Only a few studies have objectively evaluated reports of changes in halitosis after H. pylori eradication; thus, this study aimed to investigate these changes after a successful H. pylori eradication. METHODS: Between February 2015 and October 2018, 56 347 patients visited the clinic. Informed consent for participation in this study was obtained from 164 patients scheduled to undergo upper gastrointestinal endoscopy due to halitosis. Of the 91 patients with H. pylori infection, the halitosis values were evaluated as Refres breath (RB) values using a Total Gas Detector™ System and compared before and after successful H. pylori eradication, as confirmed with urea breath testing. RESULTS: Among the 91 patients treated, 77 patients were successfully eradicated of H. pylori and had their Refres values measured (21 men and 56 women; mean age, 64.2 ± 11.5 years, including 10 smokers); among these 77 patients, 27 showed RB values of > 60. Their RB values significantly improved from 73.5 Â (95% confidence interval [CI], 64.1-82.9) to 59.4 Â (95% CI, 50.0-68.8) (P = 0.038). Of the 30 patients who could be followed up for > 2 years after successful H. pylori eradication, 8 with an RB value ≥ 60 showed significant RB value improvements from 77.9 Â (95% CI, 59.4-96.4) to 30.1 Â (95% CI, 11.6-48.6) (P = 0.0016). CONCLUSIONS: Helicobacter pylori eradication therapy could improve halitosis, and such improvement could be maintained even 2 years after successful eradication.
Assuntos
Halitose , Infecções por Helicobacter , Helicobacter pylori , Idoso , Antibacterianos/uso terapêutico , Testes Respiratórios , Quimioterapia Combinada , Feminino , Halitose/diagnóstico , Halitose/tratamento farmacológico , Halitose/etiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
With the prevalence of endoscopic submucosal dissection and endoscopic full thickness resection, which enable complete resection of T1 colorectal cancer with a negative margin, the treatment strategy following endoscopic resection has become more important. The necessity of secondary surgical resection is determined on the basis of the risk of lymph node metastasis according to the histopathological findings of resected specimens because ~10% of T1 colorectal cancer cases have lymph node metastasis. The current Japanese treatment guidelines state four risk factors for lymph node metastasis: lymphovascular invasion, histological differentiation, depth of submucosal invasion, and tumor budding. These guidelines have succeeded in stratifying the low-risk group for lymph node metastasis, in which endoscopic resection alone is acceptable for cure. On the other hand, there are some problems: there is variation in diagnosis methods and low interobserver agreement for each pathological factor and 90% of surgical resections are unnecessary, with lymph node metastasis negativity. To ensure patients with T1 colorectal cancer receive more appropriate treatment, these problems should be addressed. In this systematic review, we gave some suggestions to these practical issues of four pathological factors as predictors.
Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Invasividade Neoplásica/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Targeting mutated oncogenes is an effective approach for treating cancer. The 4 main driver genes of pancreatic ductal adenocarcinoma (PDAC) are KRAS, TP53, CDKN2A, and SMAD4, collectively called the "big 4" of PDAC, however they remain challenging therapeutic targets. In this study, ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 (ASAP2), one of the ArfGAP family, was identified as a novel driver gene in PDAC. Clinical analysis with PDAC datasets showed that ASAP2 was overexpressed in PDAC cells based on increased DNA copy numbers, and high ASAP2 expression contributed to a poor prognosis in PDAC. The biological roles of ASAP2 were investigated using ASAP2-knockout PDAC cells generated with CRISPR-Cas9 technology or transfected PDAC cells. In vitro and in vivo analyses showed that ASAP2 promoted tumor growth by facilitating cell cycle progression through phosphorylation of epidermal growth factor receptor (EGFR). A repositioned drug targeting the ASAP2 pathway was identified using a bioinformatics approach. The gene perturbation correlation method showed that niclosamide, an antiparasitic drug, suppressed PDAC growth by inhibition of ASAP2 expression. These data show that ASAP2 is a novel druggable driver gene that activates the EGFR signaling pathway. Furthermore, niclosamide was identified as a repositioned therapeutic agent for PDAC possibly targeting ASAP2.
Assuntos
Carcinoma Ductal Pancreático/genética , Proteínas Ativadoras de GTPase/genética , Neoplasias Pancreáticas/genética , Animais , Carcinoma Ductal Pancreático/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes erbB-1/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/patologia , Transdução de Sinais/genéticaRESUMO
PURPOSE: Although some studies have reported differences in clinicopathological features between left- and right-sided advanced colorectal cancer (CRC), there are few reports regarding early-stage disease. In this study, we aimed to compare the clinicopathological features of left- and right-sided T1 CRC. METHODS: Subjects were 1142 cases with T1 CRC undergoing surgical or endoscopic resection between 2001 and 2018 at Showa University Northern Yokohama Hospital. Of these, 776 cases were left-sided (descending colon to rectum) and 366 cases were right-sided (cecum to transverse colon). We compared clinical (patients age, sex, tumor size, morphology, initial treatment) and pathological features (invasion depth, histological grade, lymphatic invasion, vascular invasion, tumor budding) including lymph node metastasis (LNM). RESULTS: Left-sided T1 CRC showed significantly higher rates of LNM (left-sided 12.0% vs. right-sided 5.4%, P < 0.05) and lymphatic invasion (left-sided 32.7% vs. right-sided 23.2%, P < 0.05). Especially, the sigmoid colon and rectum showed higher rates of LNM (12.4% and 12.1%, respectively) than other locations. Patients with left-sided T1 CRC were younger than those with right-sided T1 CRC (64.9 years ±11.5 years vs. 68.7 ± 11.6 years, P < 0.05), as well as significantly lower rates of poorly differentiated carcinoma/mucinous carcinoma than right-sided T1 CRC (11.6% vs. 16.1%, P < 0.05). CONCLUSION: Left-sided T1 CRC, especially in the sigmoid colon and rectum, exhibited higher rates of LNM than right-sided T1 CRC, followed by higher rates of lymphatic invasion. These results suggest that tumor location should be considered in decisions regarding additional surgery after endoscopic resection. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Network Clinical Trials Registry ( UMIN 000032733 ).
Assuntos
Colo Transverso , Neoplasias Colorretais , Humanos , Metástase Linfática , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: Recent studies have suggested the necessity of therapeutic intervention for patients with ulcerative colitis at high risk of clinical relapse with a Mayo endoscopic score (MES) of 1. The aim of this retrospective cohort study was to demonstrate the impact of intramucosal capillary network changes and crypt architecture abnormalities to stratify the risk of relapse in patients with an MES of 1. METHODS: All included patients had an MES of ≤1 and confirmed sustained clinical remission between October 2016 and April 2019. We classified patients with an MES of 1 as "intramucosal capillary/crypt (ICC)-active" or "ICC-inactive" using endocytoscopic evaluation. We followed patients until October 2019 or until relapse; the main outcome measure was the difference in clinical relapse-free rates between ICC-active and ICC-inactive patients with an MES of 1. RESULTS: We included 224 patients and analyzed data for 218 (82 ICC-active and 54 ICC-active with an MES of 1 and 82 with an MES of 0). During follow-up, among the patients with an MES of 1, 30.5% (95% confidence interval 20.8-41.6; 25/82) of the patients relapsed in the ICC-active group and 5.6% (95% confidence interval 1.2-15.4; 3/54) of the patients relapsed in the ICC-inactive group. The ICC-inactive group had a significantly higher clinical relapse-free rate compared with the ICC-active group (P < 0.01). CONCLUSIONS: In vivo intramucosal capillary network and crypt architecture patterns stratified the risk of clinical relapse in patients with an MES of 1 (UMIN 000032580; UMIN 000036359).
Assuntos
Colite Ulcerativa , Colite Ulcerativa/diagnóstico por imagem , Colonoscopia , Humanos , Mucosa Intestinal , Recidiva , Estudos RetrospectivosRESUMO
Alternative splicing, regulated by DEAD-Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT-qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56-knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2-M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1.
Assuntos
Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/patologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Amplificação de Genes , Proteínas Nucleares/genética , Proteínas Tirosina Quinases/genética , Regulação para Cima , Idoso , Animais , Ciclo Celular , Linhagem Celular Tumoral , Cromossomos Humanos Par 7/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Splicing de RNA , Análise de Sequência de RNA , Análise de SobrevidaRESUMO
BACKGROUND AND STUDY AIMS: Decisions concerning additional surgery after endoscopic resection of T1 colorectal cancer (CRC) are difficult because preoperative prediction of lymph node metastasis (LNM) is problematic. We investigated whether artificial intelligence can predict LNM presence, thus minimizing the need for additional surgery. PATIENTS AND METHODS: Data on 690 consecutive patients with T1 CRCs that were surgically resected in 2001â-â2016 were retrospectively analyzed. We divided patients into two groups according to date: data from 590 patients were used for machine learning for the artificial intelligence model, and the remaining 100 patients were included for model validation. The artificial intelligence model analyzed 45 clinicopathological factors and then predicted positivity or negativity for LNM. Operative specimens were used as the gold standard for the presence of LNM. The artificial intelligence model was validated by calculating the sensitivity, specificity, and accuracy for predicting LNM, and comparing these data with those of the American, European, and Japanese guidelines. RESULTS: Sensitivity was 100â% (95â% confidence interval [CI] 72â% to 100â%) in all models. Specificity of the artificial intelligence model and the American, European, and Japanese guidelines was 66â% (95â%CI 56â% to 76â%), 44â% (95â%CI 34â% to 55â%), 0â% (95â%CI 0â% to 3â%), and 0â% (95â%CI 0â% to 3â%), respectively; and accuracy was 69â% (95â%CI 59â% to 78â%), 49â% (95â%CI 39â% to 59â%), 9â% (95â%CI 4â% to 16â%), and 9â% (95â%CI 4â%â-â16â%), respectively. The rates of unnecessary additional surgery attributable to misdiagnosing LNM-negative patients as having LNM were: 77â% (95â%CI 62â% to 89 %) for the artificial intelligence model, and 85â% (95â%CI 73â% to 93â%; Pâ<â0.001), 91â% (95â%CI 84â% to 96â%; Pâ<â0.001), and 91â% (95â%CI 84â% to 96â%; Pâ<â0.001) for the American, European, and Japanese guidelines, respectively. CONCLUSIONS: Compared with current guidelines, artificial intelligence significantly reduced unnecessary additional surgery after endoscopic resection of T1 CRC without missing LNM positivity.
Assuntos
Inteligência Artificial/estatística & dados numéricos , Neoplasias Colorretais , Erros de Diagnóstico , Endoscopia , Metástase Linfática/diagnóstico , Procedimentos Desnecessários/estatística & dados numéricos , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Erros de Diagnóstico/prevenção & controle , Erros de Diagnóstico/estatística & dados numéricos , Endoscopia/métodos , Endoscopia/normas , Feminino , Heurística , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Estadiamento de Neoplasias , Prognóstico , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The recurrence of T1 colorectal cancers is relatively rare, and the prognostic factors still remain obscure. This study aimed to clarify the risk factors for recurrence in patients with T1 colorectal cancers treated by endoscopic resection (ER) alone or surgical resection (SR) with lymph node dissection, respectively. METHODS: We reviewed 930 patients with resected T1 colorectal cancers (mean follow-up, 52.3 months). Patients were divided into two groups: those who underwent ER alone (298 cases), and those who underwent initial or additional SR with lymph node dissection (632 cases). Group differences in recurrence-free survival were evaluated using the Kaplan-Meier method and log-rank test. Associations between recurrence and clinicopathological features were evaluated in Cox regression analyses; hazard ratios (HRs) were calculated for the total population and each group. RESULTS: Recurrence occurred in four cases (1.34%) in the ER group and six cases (0.95%) in the SR group (p = 0.32). Endoscopic resection, rectal location, and poor or mucinous (Por/Muc) differentiation were prognostic factors for recurrence in the total population. Por/Muc differentiation was prognostic factor in both groups. Female sex, depressed-type morphology, and lymphatic invasion were also prognostic factors in the ER group, but not in the SR group. CONCLUSIONS: Endoscopic resection, rectal location, and Por/Muc differentiation are prognostic factors in the total population. For patients who undergo ER alone, female sex, depressed-type morphology, and lymphatic invasion are also risk factors for recurrence. For such patients, regional en-bloc surgery with lymph node dissection could reduce the risk of recurrence.
Assuntos
Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Metástase Linfática , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: Submucosal invasion depth (SID) in colorectal carcinoma (CRC) is an important factor in estimating risk of lymph node metastasis, but can be difficult to measure, leading to inadequate or over-extensive treatment. Here, we aimed to clarify the practical aspects of measuring SID in T1 CRC. METHODS: We investigated 568 T1 CRCs that were resected surgically at our hospital from April 2001 to December 2013, and relationships between SID and clinicopathological factors, including the means of measurement, lesion morphology, and lymph node metastasis. RESULTS: Of these 568 lesions, the SID was ≥1000 µm in 508 lesions. SIDs for lesions measured from the surface layer were all ≥1000 µm. Although lesions with SIDs ≥1000 µm were associated with significantly higher levels of unfavorable histologic types and lymphovascular infiltration than shallower lesions, a depth of ≥1000 µm was not a significant risk factor for lymph node metastasis (LNM) (6.7 vs. 9.8 %; P = 0.64), and no lesions for which the sole pathological factor was SID ≥1000 µm had lymph node metastasis. Protruded lesions showed deeper SIDs than other types. CONCLUSIONS: Although we found several problems of measuring SID in this study, we also found, surprisingly, that SID is not a risk factor for lymph node metastasis, and its measurement is not needed to estimate the risk of lymph node metastasis.
Assuntos
Neoplasias Colorretais/patologia , Mucosa Intestinal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
BACKGROUND AND AIM: Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas to be resected endoscopically with negative margins. However, the criteria for curative endoscopic resection remain unclear. We aimed to identify risk factors for nodal metastasis in T1 carcinoma patients and hence establish the indication for additional surgery with lymph node dissection. METHODS: Initial or additional surgery with nodal dissection was performed in 653 T1 carcinoma cases. Clinicopathological factors were retrospectively analyzed with respect to nodal metastasis. The status of the muscularis mucosae (MM grade) was defined as grade 1 (maintenance) or grade 2 (fragmentation or disappearance). The lesions were then stratified based on the risk of nodal metastasis. RESULTS: Muscularis mucosae grade was associated with nodal metastasis (P = 0.026), and no patients with MM grade 1 lesions had nodal metastasis. Significant risk factors for nodal metastasis in patients with MM grade 2 lesions were attribution of women (P = 0.006), lymphovascular infiltration (P < 0.001), tumor budding (P = 0.045), and poorly differentiated adenocarcinoma or mucinous carcinoma (P = 0.007). Nodal metastasis occurred in 1.06% of lesions without any of these pathological factors, but in 10.3% and 20.1% of lesions with at least one factor in male and female patients, respectively. There was good inter-observer agreement for MM grade evaluation, with a kappa value of 0.67. CONCLUSIONS: Stratification using MM grade, pathological factors, and patient sex provided more appropriate indication for additional surgery with lymph node dissection after endoscopic treatment for T1 colorectal carcinomas.
Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Colectomia/métodos , Colonoscopia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Adenocarcinoma/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Neoplasias Colorretais/química , Desmina/análise , Feminino , Humanos , Imuno-Histoquímica , Japão , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Variações Dependentes do Observador , Seleção de Pacientes , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Previous reports stated that pedunculated T1 colorectal carcinomas with 'head invasion' showed almost no nodal metastasis, requiring endoscopic treatment alone. However, clinically, some lesions develop nodal metastasis. We aimed to validate the necessity of distinguishing between 'pedunculated' and 'non-pedunculated' lesions, and also between 'head' and 'stalk' invasions. METHODS: Initial or additional surgery with lymph node dissection was performed in 76 pedunculated and 594 non-pedunculated cases. Among pedunculated lesions, the baseline was defined as the junction line between normal and neoplastic epithelium (Haggitt's level 2). The degree of invasion was classified as 'head invasion' (above the baseline) or 'stalk invasion' (beyond the baseline). Clinicopathological factors were analyzed with respect to nodal metastasis. RESULTS: Nine of 76 (11.8%) pedunculated cases and 52/594 (8.8%) non-pedunculated cases developed nodal metastasis (p = 0.40). No significant differences were found in the rate of nodal metastasis between 'head invasion' (4/30, 13.3%) and 'stalk invasion' (5/46, 10.9%). All the 4 cases with 'head invasion' had at least one pathological factor. CONCLUSIONS: 'Head invasion' was not a metastasis-free condition. Even for pedunculated T1 cancers with 'head invasion', additional surgery with lymph node dissection should be considered if these have pathological risk factors.
Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Mucosa Intestinal/patologia , Linfonodos/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Endoscopia , Feminino , Humanos , Mucosa Intestinal/cirurgia , Japão , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Fatores de RiscoRESUMO
Submucosal invasive (T1) colorectal cancer is a significant clinical management challenge, with an estimated 10% of patients developing extraintestinal lymph node metastasis. This condition necessitates surgical resection along with lymph node dissection to achieve a curative outcome. Thus, the precise preoperative assessment of lymph node metastasis risk is crucial to guide treatment decisions after endoscopic resection. Contemporary clinical guidelines strive to identify a low-risk cohort for whom endoscopic resection will suffice, applying stringent criteria to maximize patient safety. Those failing to meet these criteria are often recommended for surgical resection, with its associated mortality risks although it may still include patients with a low risk of metastasis. In the quest to enhance the precision of preoperative lymph node metastasis risk prediction, innovative models leveraging artificial intelligence or nomograms are being developed. Nevertheless, the debate over the ideal sensitivity and specificity for such models persists, with no consensus on target metrics. This review puts forth postoperative mortality rates as a practical benchmark for the sensitivity of predictive models. We underscore the importance of this method and advocate for research to amass data on surgical mortality in T1 colorectal cancer. Establishing specific benchmarks for predictive accuracy in lymph node metastasis risk assessment will hopefully optimize the treatment of T1 colorectal cancer.
RESUMO
Objectives: Japanese guidelines include high-grade (poorly differentiated) tumors as a risk factor for lymph node metastasis (LNM) in T1 colorectal cancer (CRC). However, whether the grading is based on the least or most predominant component when the lesion consists of two or more levels of differentiation varies among institutions. This study aimed to investigate which method is optimal for assessing the risk of LNM in T1 CRC. Methods: We retrospectively evaluated 971 consecutive patients with T1 CRC who underwent initial or additional surgical resection from 2001 to 2021 at our institution. Tumor grading was divided into low-grade (well- to moderately differentiated) and high-grade based on the least or predominant differentiation analyses. We investigated the correlations between LNM and these two grading analyses. Results: LNM was present in 9.8% of patients. High-grade tumors, as determined by least differentiation analysis, accounted for 17.0%, compared to 0.8% identified by predominant differentiation analysis. A significant association with LNM was noted for the least differentiation method (p < 0.05), while no such association was found for predominant differentiation (p = 0.18). In multivariate logistic regression, grading based on least differentiation was an independent predictor of LNM (p = 0.04, odds ratio 1.68, 95% confidence interval 1.00-2.83). Sensitivity and specificity for detecting LNM were 27.4% and 84.1% for least differentiation, and 2.1% and 99.3% for predominant differentiation, respectively. Conclusions: Tumor grading via least differentiation analysis proved to be a more reliable measure for assessing LNM risk in T1 CRC compared to grading by predominant differentiation.
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The incidence of T1 colorectal cancer is expected to increase because of the prevalence of colorectal cancer screening and the progress of endoscopic treatment such as endoscopic submucosal dissection or endoscopic full-thickness resection. Currently, the requirement for additional surgery after endoscopic resection of T1 colorectal cancer is determined according to several treatment guidelines (in USA, Europe, and Japan) referring to the following pathological findings: lymphovascular invasion, tumor differentiation, depth of invasion, and tumor budding, all of which are reported to be risk factors for lymph node metastasis. In addition to these factors, in this review, we investigate whether tumor location, which is an objective factor, has an impact on the presence of lymph node metastasis and recurrence. From recent studies, left-sided location, especially the sigmoid colon in addition to rectum, could be a risk factor for lymph node metastasis and cancer recurrence. The treatment of T1 colorectal cancer should be managed considering these findings.
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BACKGROUND: Colorectal cancer (CRC) can be classified into four consensus molecular subtypes (CMS) according to genomic aberrations and gene expression profiles. CMS is expected to be useful in predicting prognosis and selecting chemotherapy regimens. However, there are still no reports on the relationship between the morphology and CMS. METHODS: This retrospective study included 55 subjects with T2 CRC undergoing surgical resection, of whom 30 had the depressed type and 25 the protruded type. In the classification of the CMS, we first defined cases with deficient mismatch repair as CMS1. And then, CMS2/3 and CMS4 were classified using an online classifier developed by Trinh et al. The staining intensity of CDX2, HTR2B, FRMD6, ZEB1, and KER and the percentage contents of CDX2, FRMD6, and KER are input into the classifier to obtain automatic output classifying the specimen as CMS2/3 or CMS4. RESULTS: According to the results yielded by the online classifier, of the 30 depressed-type cases, 15 (50%) were classified as CMS2/3 and 15 (50%) as CMS4. Of the 25 protruded-type cases, 3 (12%) were classified as CMS1 and 22 (88%) as CMS2/3. All of the T2 CRCs classified as CMS4 were depressed CRCs. More malignant pathological findings such as lymphatic invasion were associated with the depressed rather than protruded T2 CRC cases. CONCLUSIONS: Depressed-type T2 CRC had a significant association with CMS4, showing more malignant pathological findings such as lymphatic invasion than the protruded-type, which could explain the reported association between CMS4 CRC and poor prognosis.