The role of tumor-infiltrating lymphocytes (TILs) in predicting lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC) remains unclear. Furthermore, clinical utility of a machine learning-based approach has not been widely studied.Materials and Methods Immunohistochemistry for TILs against CD3, CD8, and forkhead box P3 in both center and invasive margin of the tumor were performed using surgically resected T1 CRC slides. Three hundred and sixteen patients were enrolled and categorized into training (n=221) and validation (n=95) sets via random sampling. Using clinicopathologic variables including TILs, the least absolute shrinkage and selection operator (LASSO) regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of our model and the Japanese criteria were compared using area under the receiver operating characteristic (AUROC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis (DCA) in the validation set.Results LNM was detected in 29 (13.1%) and 12 (12.6%) patients in training and validation sets, respectively. Nine variables were selected and used to generate the LASSO model. Its performance was similar in training and validation sets (AUROC, 0.795 vs. 0.765; p=0.747). In the validation set, the LASSO model showed better outcomes in predicting LNM than Japanese criteria, as measured by AUROC (0.765 vs. 0.518, p=0.003) and NRI (0.447, p=0.039)/IDI (0.121, p=0.034). DCA showed positive net benefits in using our model.
ConclusionOur LASSO model incorporating histopathologic parameters and TILs showed superior performance compared to conventional Japanese criteria in predicting LNM in patients with T1 CRC.
In conclusion, identifying the anatomical location of the SMV and performing meticulous dissection along the SMV is an essential procedure for containing all potential routes of metastatic tumors. Initial ileocecal mobilization with adequate counter traction of the cecum may be useful for novice surgeons attempting to identify the location of SMV during laparoscopic CME for right colon cancer.
PurposePredicting the need for surgical intervention among patients with intestinal obstruction is challenging. The delta neutrophil index (DNI) has been suggested as a useful marker of immature granulocytes, which indicate an infection or sepsis. In this study, we evaluated the impact of the DNI as an early predictor of operation among patients with intestinal obstruction.MethodsA total of 171 patients who were diagnosed with postoperative intestinal obstruction were enrolled in this study. Medical records, including data for the initial CRP level, WBC count, and DNI were reviewed. Receiver operating characteristic (ROC) curves were generated to clarify the optimal DNI cutoff values for predicting an operation.ResultsAmong the 171 patients, 38 (22.2%) needed surgical intervention. The areas under the initial CRP, WBC, and DNI ROC curves were 0.460, 0.449, and 0.543, respectively. The optimal cutoff value for predicting further surgical intervention according to the initial DNI level was 4.3%. The accuracy of the cutoff value was 74.9%, the sensitivity was 23.7%, and the specificity was 89.5% (positive predictive value, 23.7%; negative predictive value, 89.5%). In the multivariate analysis, initial DNI levels ≥ 4.3% were significantly associated with surgical intervention (odd ratio, 3.092; 95% confidence interval, 1.072–8.918; P = 0.037).ConclusionThe initial DNI level in patients with intestinal obstruction may be a useful predictor for determining the need for surgical intervention.
Specific protein 1 (SP1) is associated with aggressive behavior, invasive clinical phenotype and poor clinical outcomes in various cancers. We studied whether SP1 exerts its effect on invasiveness and promotion of the epithelial-mesenchymal transition (EMT) by regulating lysyl oxidase-like 2 (LOXL2) in pancreatic ductal adenocarcinoma (PDAC) cell lines. We showed that silencing of SP1 in MIA Paca-2 cell significantly decreased cell invasion and migration. In MIA Paca-2 cells, silencing of SP1 induced a reduction of LOXL2 expression, whereas LOXL2 silencing did not lead to a decrease in the expression of SP1. Chromatin immunoprecipitation assay demonstrated the binding of SP1 to LOXL2 promoter. Wound healing and transmigration assays also showed that transfection of both SP1 and LOXL2 siRNA induced most significant decrease of cell invasion and migration compared to either SP1 or LOXL2-only silenced cells. Finally, we investigated the prognostic value of SP1 in patients with PDAC and SP1/LOX2 expression was examined by immunochemistry. Univariate and multivariate analyses showed that tumor differentiation and co-expression of SP1 and LOXL2 were independent factors for disease-free survival. In summary, our study demonstrates that SP1 modulates EMT and is involved in tumor invasion and migration of PDAC cells through the regulation of LOXL2.
PCT was associated with higher lymph node yield in T1 colorectal cancer. It is questionable if tattooing has additional detection power as a sentinel lymph node mapping tool in T1 colorectal cancer.
PurposeThe estimation of regional lymph node metastasis (LNM) risk in T1 colorectal cancer is based on histologic examination and imaging of the primary tumor. High-frequency microsatellite instability (MSI-H) is likely to decrease the possibility of metastasis to either regional lymph nodes or distant organs in colorectal cancers. This study evaluated the clinical implications of MSI in T1 colorectal cancer with emphasis on the usefulness of MSI as a predictive factor for regional LNM.Materials and MethodsA total of 133 patients who underwent radical resection for T1 colorectal cancer were included. Genomic DNA was extracted from normal and tumor tissues and amplified by polymerase chain reaction (PCR). Five microsatellite markers, BAT-25, BAT-26, D2S123, D5S346, and D17S250, were used. MSI and clinicopathological parameters were evaluated as potential predictors of LNM using univariate and multivariate analyses.ResultsAmong 133 T1 colorectal cancer patients, MSI-H, low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS) colorectal cancers accounted for 7.5%, 6%, and 86.5%, respectively. MSI-H tumors showed a female predominance, a proximal location and more retrieved lymph nodes. Twenty-two patients (16.5%) had regional LNM. Lymphovascular invasion and depth of invasion were significantly associated with LNM. There was no LNM in 10 MSI-H patients; however, MSI status was not significantly correlated with LNM. Disease-free survival did not differ between patients with MSI-H and those with MSI-L/MSS.ConclusionMSI status could serve as a negative predictive factor in estimating LNM in T1 colorectal cancer, given that LNM was not detected in MSI-H patients. However, validation of our result in a different cohort is necessary.
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