Characteristics of minute T1 colorectal cancer in relevance to pathology and treatment.
ABSTRACT: Purpose:Minute T1 colorectal cancer (CRC) lesions (?5 mm) are rare; however, little is known about their characteristics and aggressiveness. In this study, we evaluated the characteristics of minute T1 CRC in relevance to pathology and treatment. Methods:This retrospective study included 849 patients with T1 CRC endoscopically or surgically treated between January 2001 and December 2016. The patients were stratified into 4 groups according to tumor size; minute group (?5 mm), small group (6-10 mm), medium group (11-20 mm), and large group (?21 mm). Clinicopathological variables were evaluated with respect to tumor size. Results:The incidence of the minute T1 CRC was 2.4% (20 of 849). Minute T1 CRC was significantly associated with flat type (minute, 25%; small, 12.6%; medium, 8.8%; large, 12.6%; P = 0.016), right-sided cancer (30%, 15.4%, 15.4%, 15.1%, P = 0.002) and the absence of background adenoma (BGA) (50%, 40.7%, 32.8%, 18.1%, P < 0.001). In patients who underwent surgery, lymph node metastasis (LNM) was significantly higher in the minute group (36.4%, 15.9%, 15.7%, 9.2%, P = 0.029). Conclusion:Minute T1 CRC is significantly associated with flat type, right-sided cancers, as well as with the absence of BGA and LNM. These results suggested the minute T1 CRC lesions are often aggressive and are likely to be missed during colonoscopy.
Project description:BACKGROUND:It is critical for determining the optimum therapeutic solutions for T1-2 colorectal cancer (CRC) to accurately predict lymph node metastasis (LNM) status. The purpose of the present study is to establish and verify a nomogram to predict LNM status in T1-2 CRCs. METHODS:A total of 16 600 T1-2 CRC patients were enrolled and classified into the training, internal validation, and external validation cohorts. The independent predictive parameters were determined by univariate and multivariate analyses to develop a nomogram to predict the probability of LNM status. The calibration curve, the area under the receiver operating characteristic curve (AUROC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram, and an external verification cohort was to verify the applicability of the nomogram. RESULTS:Seven independent predictors of LNM in T1-2 CRC were identified in the multivariable analysis, including age, tumor site, tumor grade, perineural invasion, preoperative carcinoembryonic antigen, clinical assessment of LNM, and T stage. A nomogram incorporating the seven predictors was constructed. The nomogram yielded good discrimination and calibration, with AUROCs of 0.72 (95% confidence interval [CI]: 0.70-0.75), 0.70 (95% CI: 0.67-0.74), and 0.74 (95% CI: 0.71-0.79) in the training, internal validation, and external validation cohorts, respectively. DCA showed that the predictive scoring system had high clinical application value. CONCLUSIONS:We proposed a novel predictive model for LNM in T1-2 CRC patients to assist physicians in making treatment decisions. The nomogram is advantageous for tailoring therapy in T1-2 CRC patients.
Project description: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 ).
Project description:If we can more accurately predict the likelihood of regional lymph node metastasis (LNM) for endoscopically resected T1-stage colorectal cancers (CRC), the number of unnecessary additional surgeries can be reduced. We aimed of identify miRNA markers that can predict LNM-positive tumors among T1-stage CRCs and we also developed a miRNA classifier set for facilitating the accuracy and applicability. Overall design: Tumor cell rich areas (>70% of tumor cells) were selected and microdissected under a microscope. Total RNA was extracted using the RecoverAll™ Total Nucleic Acid Isolation Kit for FFPE. Then, we examined global miRNA expression profiles from 16 T1-stage CRCs (7 LNM-positive and 9 LNM- negative tumors) using miRNA-array analysis.
Project description:Background:Endoscopic resection is increasingly used to treat pathological T1 (pT1) esophageal cancer (EC) patients. However, the procedures are limited by lymph node metastasis (LNM) and remain controversial. We aimed to construct a nomogram to predict the risk of LNM in patients with pT1 esophageal squamous cell carcinoma (ESCC). Methods:A total of 243 patients with pT1 ESCC who underwent esophagectomy and lymph node dissection at two different institutes between February 2013 and June 2019 were analyzed retrospectively. Patients were categorized into the negative group and the positive group according to whether there was LNM. Risk factors for LNM were evaluated by univariate and multivariate analyses. The nomogram was used to estimate the individual risk of LNM. Results:Forty-six (18.9%) of the 243 patients with pT1 ESCC exhibited LNM. The LNM rate in patients with stage T1a disease was 5.7% (5/88), and the rate in patients with stage T1b disease was 26.5% (41/155). Multivariable logistic regression analysis showed that tumor differentiation [odds ratio (OR) =1.942, 95% confidence interval (CI): 1.067-3.536, P=0.030], the T1 sub-stage (OR =4.750, 95% CI: 1.658-13.611, P=0.004), the preoperative alanine aminotransferase/aspartate aminotransferase ratio (LSR) (OR =5.371, 95% CI: 1.676-17.210, P=0.005), and the high-density lipoprotein cholesterol (HDL-C) level (OR =5.894, 95% CI: 1.917-18.124, P=0.002) were independent risk factors for LNM. The nomogram had relatively high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.803 (95% CI: 0.732-0.873). The calibration curve showed that the predicted probability of LNM was in good agreement with the actual probability. Conclusions:Clinicopathological and hematological parameters of tumor differentiation, the T1 sub-stage, the preoperative LSR, and the HDL-C level may predict the risk of LNM in T1 ESCC. The risk of LNM can be predicted by the nomogram.
Project description:BACKGROUND:Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors. METHODS:EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n?=?1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n?=?172) were selected as the validation set. RESULTS:In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P?=?0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20?mm, submucosal invasion and undifferentiated tumor histological type (all P?<? 0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P?<? 0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set. CONCLUSIONS:The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested.
Project description:Endoscopic resection (ER) has been increasingly performed in the treatment of early gastric cancer (GC). However, lymph node metastasis (LNM) can cause treatment failure with ER, especially in T1b patients. Here, we attempted to develop a miRNA-based classifier to detect LNM in T1b patients. Based on high-throughput data from The Cancer Genome Atlas, we identified 20 miRNAs whose expression significantly changed in T1-2 GC with LNM vs T1-2 GC without LNM. We then developed a miRNA signature to predict LNM of T1b GC using the LASSO model and backward step wise elimination approach in a training cohort. Furthermore, the predictive accuracy of this classifier was validated in both an internal testing group of 63 patients and an external independent group of 114 patients. This systematic and comprehensive in silico study identified a 7-miRNA signature with an area under the receiver operating characteristic curve (AUROC) value of 0.843 in T1-2 GC and 0.911 in T1 EGC. The backward elimination was further used to develop a 4-miRNA (miR-153-3p, miR-708, miR-940 and miR-375) risk-stratification model in the training cohort with an AUROC value of 0.898 in cohort 2. When pathologic results were used as a reference, the risk model yielded AUROC values of 0.829 and 0.792 in two cohorts of endoscopic biopsy specimens. This novel miRNA-LNM classifier works better than the currently used pathologic criteria of ER in T1b EGC. This classifier could individualize the management of T1b patients and facilitate treatment decisions.
Project description:Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Lymph node metastasis (LNM) is a common mode of metastasis of CRC. However, the combined mRNA biomarkers associated with LNM of CRC that can effectively predict CRC prognosis have not been reported yet. Methods: To identify biomarkers that are associated with LNM, we collected data from the The Cancer Genome Atlas (TCGA) database. The edgeR package was searched to seek LNM-related genes by comparisons between cancer samples and normal colorectal tissues and between LNM and non-LNM (NLNM) of CRC. Univariate and multivariate regression analysis of genes in the intersection to build gene signature associated with independent prognosis of CRC, and then verified by Kaplan-Meier curve and log-rank test, receiver operating characteristic (ROC) curve was used to determine the efficiency of survival prediction of our four-mRNA signature. Finally, the potential molecular mechanisms and properties of these gene signature were also explored with functional and pathway enrichment analysis. Results: 329 mRNAs were up-regulated in CRC tissues with LNM, and 8461 mRNAs were up-regulated in CRC tissues, the intersection is 100 mRNAs. After univariate and multivariate Cox regression analysis of 100 mRNAs, a novel four LNM related mRNAs (EPHA8, KRT85, GABRA3, and CLPSL1) were screened as independent prognostic indicators of CRC. Surprisingly, the four-mRNA signature can predict the prognosis of CRC patients independently of clinical factors andthe area under the curve (AUC) of the ROC is 0.730. The novel four-mRNA signature was used to identify high and low-risk groups. Stratified analysis indicated the risk score based on four-mRNA signature was an independent prognostic indicator for female, T3+T4, N1+N2 ,stage III+IV and patients with no new tumor event. Functional annotation of this risk model in high-risk patients revealed that pathways associated with neuroactive ligand-receptor interaction, estrogen signaling pathway, and steroid hormone biosynthesis. Conclusions: By conducting TCGA data mining, our study demonstrated that a four-mRNA signature associated with LNM can be used as a combined biomarker for independent prognosis of CRC.
Project description:Background and study aims ?Based on pathology, locally resected T1 colorectal cancer (T1-CRC) can be classified as having low- or high-risk for irradicality and/or lymph node metastasis, the latter requiring adjuvant surgery. Reporting and application of pathological high-risk criteria is likely variable, with inherited variation regarding baseline oncological staging, treatment and surveillance. Methods ?We assessed practice variation using an online survey among gastroenterologists and surgeons participating in the Dutch T1-CRC Working Group. Results ?Of the 130 invited physicians, 53?% participated. Regarding high-risk T1-CRC criteria, lymphangio-invasion is used by 100?%, positive or indeterminable margins by 93?%, poor differentiation by 90?%, tumor-free margin ??1?mm by 78?%, tumor budding by 57?% and submucosal invasion >?1000?µm by 47?%. Fifty-two percent of the respondents do not perform baseline staging in locally resected low-risk T1-CRC. In case of unoperated high-risk patients, we recorded 61 different surveillance strategies in 63 participants, using 19 different combinations of diagnostic tests. Endoscopy is used in all schedules. Mean follow-up time is 36 months for endoscopy, 26 months for rectal MRI and 30 months for abdominal CT (all varying 3-60 months). Conclusion ?We found variable use of pathological high-risk T1-CRC criteria, creating risk for misclassification as low-risk T1-CRC. This has serious implications, as most participants will not proceed to oncological staging in low-risk patients and adjuvant surgery nor radiological surveillance is considered. On the other hand, oncological surveillance in patients with a locally resected high-risk T1-CRC who do not wish adjuvant surgery is highly variable emphasizing the need for a uniform surveillance protocol.
Project description:Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.
Project description:Abstract Aim Although rectal neuroendocrine tumors (NETs) are considered to be rare low?grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk?scoring system for LNM to help determine appropriate therapeutic approaches. Methods In this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade. Results According to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ? 15 mm and muscularis invasion, and 1 point each for SM depth ? 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843?0.955). When a score of 2 was used as the cut?off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively. Conclusions The risk?scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk?scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658. The risk?scoring system for LNM of rectal NETs could predict the risk of LNM and thereby potentially avoid unnecessary surgery.