High Expression of Ubiquitin-Specific Protease 39 and Its Roles in Prognosis in Patients with Hepatocellular Carcinoma

Background. Ubiquitin-specific protease 39 is mainly involved in mRNA splicing and multiple kinds of tumors. Accumulating evidence has shown that USP39 participated in the proliferation and metastasis of hepatocellular carcinoma (HCC). The present study aimed to demonstrate the association between USP39 expression and clinical features and the diagnostic value in HCC based on the Cancer Genome Atlas (TCGA). Methods. A comprehensive analysis for expression of USP39 in HCC was conducted by using multiple databases. The mRNA level of USP39, clinical features, survival rate, and diagnostic value in HCC were analyzed using data from TCGA. The Gene Set Enrichment Analysis (GSEA) was conducted to analyze signaling pathways correlated with USP39 expression in HCC. Results. The mRNA level of USP39 was significantly elevated in HCC. The expression of USP39 showed significant correlation with T stage, pathologic stage, tumor status, age, and histologic grade. Logistic analysis demonstrated that high expression of USP39 was significantly associated with older age, tumor status, advanced pathologic stage, T stage, and higher histologic grade. Univariate Cox regression analysis showed that high expression of USP39 was significantly associated with advanced T stage, pathological stage, and tumor status. Multivariate Cox analysis confirmed the result that USP39 expression was an independent prognostic factor for overall survival (OS) in HCC. Results of Kaplan–Meier curves showed that high expression of USP39 had a significant association with poor OS, disease-free survival (DSS), and progress-free interval (PFI) in HCC. ROC analysis indicated that USP39 could be regarded as a promising marker for distinguishing HCC from nontumor. Conclusion. The increased USP39 might play roles in the progression, diagnosis, and prognosis of HCC.

Exploration of a Modified Stage for pN0 Colon Cancer Patients

Purpose: Exploring a modified stage (mStage) for pN0 colon cancer patients.Methods: 39637 pN0 colon cancer patients were collected from the SEER database (2010-2015) (development cohort) and 455 pN0 colon cancer patients from the Second Affiliated Hospital of Harbin Medical University (2011-2015) (validation cohort). The optimal lymph nodes examined (LNE) stratification for cancer-specific survival (CSS) was obtained by X-tile software. LNE is combined with conventional T stage to form the mStage.Results: The novel N stage was built based on the LNE (N0a: LNE ≥ 26, N0b: LNE = 10-25 and N0c: LNE < 10). The mStage include mStageA (T1N0a, T1N0b, T1N0c and T2N0a), mStageB (T2N0b, T2N0c and T3N0a), mStageC (T3N0b), mStageD (T3N0c, T4aN0a and T4bN0a), mStageE (T4aN0b and T4bN0b) and mStageF (T4aN0c and T4bN0c). Cox regression model showed that mStage was an independent prognostic factor. AUC showed that the predictive accuracy of mStage was better than the conventional T stage for 5-year CSS in the development (0.700 vs 0.678, P < 0.001) and validation cohort (0.649 vs 0.603, P = 0.018). The C-index also showed that mStage had a superior model-fitting.Conclusions: For pN0 colon cancer patients, mStage might be superior to conventional T stage in predicting the prognosis.

A Population-Based Study: How to Identify High-Risk T1–2 Esophageal Cancer Patients?

BackgroundDue to individualized conditions of lymph node metastasis (LNM) and distant metastasis (DM), the following therapeutic strategy and diagnosis of T1–2 esophageal cancer (ESCA) patients are varied. A prediction model for identifying risk factors for LNM, DM, and overall survival (OS) of high-risk T1–2 ESCA patients is of great significance to clinical practice.MethodsA total of 1,747 T1–2 ESCA patients screened from the surveillance, epidemiology, and end results (SEER) database were retrospectively analyzed for their clinical data. Univariate and multivariate logistic regression models were established to screen out risk factors for LNM and DM of T1-2 ESCA patients, while those of OS were screened out using the Cox regression analysis. The identified risk factors for LNM, DM, and OS were then subjected to the establishment of three nomograms, respectively. The accuracy of the nomograms was evaluated by depicting the calibration curve, and the predictive value and clinical utility were evaluated by depicting the clinical impact curve (CIC) and decision curve analysis (DCA), respectively.ResultsThe age, race, tumor grade, tumor size, and T-stage were significant factors for predicting LNM of T1–2 ESCA patients (p &lt; 0.05). The age, T-stage, tumor grade, and tumor size were significant factors for predicting DM of T1–2 ESCA patients (p &lt; 0.05). The age, race, sex, histology, primary tumor site, tumor size, N-stage, M-stage, and surgery were significant factors for predicting OS of T1–2 ESCA patients (p &lt; 0.05). The C-indexes of the three nomograms constructed by these factors were 0.737, 0.764, and 0.740, respectively, suggesting that they were clinically effective.ConclusionsThe newly constructed nomograms can objectively and accurately predict the LNM, DM, and OS of T1–2 ESCA patients, which contribute to the individualized decision making before clinical management.

Combination of C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio as a Novel Prognostic Index in Patients With Bladder Cancer After Radical Cystectomy

BackgroundInflammation is widely considered an important hallmark of cancer and associated with poor postoperative survival. The objective of this study is to assess the significance of preoperative C-NLR, a new inflammation-based index that includes preoperative C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), on therapeutic outcomes for bladder cancer (BC) patients after radical cystectomy (RC).Materials and MethodsBC patients who underwent RC between 2010 and 2019 were retrospectively analyzed from our medical center. The predictive effect of CRP, NLR, and C-NLR on the survival of BC patients were analyzed by the receiver operating characteristic (ROC) curves. The relationship between C-NLR and postoperative survival was investigated by Cox regression. The corresponding nomograms were built based on the Cox regression results of overall survival (OS) and disease-free survival (DFS), which were further validated by ROC curves, decision curve analysis (DCA) curves, and calibration curves.ResultsOf the 199 eligible patients, 83 (41.70%) were classified as high C-NLR group and the remaining 116 (58.30%) were classified as low C-NLR group. ROC analysis showed that C-NLR had the largest area under curve (AUC) compared to CRP and NLR. Multivariate analysis revealed that T-stage and C-NLR [high C-NLR vs. low C-NLR, hazard ratio (HR) = 2.478, 95% confidence interval (CI), 1.538–3.993, p &lt; 0.001] were independent predictors of OS, whereas T-stage, M-stage, and C-NLR (high C-NLR vs. low C-NLR, HR = 2.817, 95% CI, 1.667–4.762, p &lt; 0.001) were independent predictors of DFS. ROC and DCA analysis demonstrated better accuracy and discrimination of 3- and 5-year OS and DFS with C-NLR-based nomogram compared to TNM stage. The calibration curve reconfirmed the accurate predicting performance of nomograms.ConclusionC-NLR is a reliable predictor of long-term prognosis of BC patients after RC and will contribute to the optimization of individual therapy for BC patients.

Anemia can predict the prognosis of colorectal cancer in the pre-operative stage: a retrospective analysis

Background Early detection of colorectal cancer (CRC) improves prognosis, yet many CRCs are diagnosed following symptoms. The aim of this study was to determine which CRC-related symptoms or signs can predict an advanced CRC in the pre-operative stage. Methods Retrospective analysis of 300 patients who underwent surgery for CRC between the years 2008 and 2019. Patients’ symptoms prior to CRC diagnosis were documented. Primary endpoint was the association of signs or/and symptoms with CRC diagnosis at TNM stages of 2–4 (i.e., highly advanced), compared to TNM score of 0–1 (i.e., locally advanced). Results Three hundred patients, 91 with locally advanced and 209 with highly advanced CRC, were enrolled. There was a significant correlation between highly advanced CRC, compared to locally advanced, regarding tumor size (4.8 vs. 2.6 cm, p<0.001), presentation of any symptom prior to diagnosis (77% vs. 54%, p<0.001), anemia (46% vs. 29%, p=0.004), and severe anemia (17% vs. 4%, p=0.002). Mean hemoglobin was 12.2 ± 2.2 and 13.1 ± 1.8 in the highly advanced compared to locally advanced CRC, respectively, p<0.001. Anemia correlated with the T stage of the tumor: 21% of patients diagnosed at stages 0–1 had anemia, 39% at stage 2, 44% at stage 3, and 66% at stage 4 (p=0.001). Conclusions Anemia is the only finding that correlates with highly advanced CRC, in the pre-operative stage. When CRC has been diagnosed, the presence of anemia, at any level, may be considered in determining prognosis at the pre-operative stage. Physicians should be aware that when anemia is present, the risk for highly advanced CRC increases, and therefore should pursue with CRC detection.

Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study

PurposePathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC.MethodsPatients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals.ResultsThere were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan–Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1–2) or advanced T stage (T3–4).ConclusionsPathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.

Oncological Outcomes of Transoral Laryngeal Microsurgery with Fiber-Optic Diode Laser for Early Glottic Cancer: A Single-Center Experience

<b><i>Backgroud/Objectives:</i></b> Transoral laser laryngeal microsurgery (_LTLM) has been widely used in the treatment of early-stage glottic laryngeal squamous cell carcinoma (LSCC) for the past few decades. Although T stage, tumor grade, anterior commissure involvement, type of cordectomy, positive surgical margin, and postoperative additional therapies were accused as the prognostic factors for recurrence, there is still controversy about these data in the literature. The purpose of this study was to evaluate the oncological results of our patients with early glottic LSCC treated with _LTLM as a single-modality therapy in a single-center study. <b><i>Methods:</i></b> Patients with early-stage (T_is-1–2/N₀) glottic LSCC who underwent _LTLM as a primary treatment from 2011 to 2019 were retrospectively reviewed. The clinicopathological factors and oncologic outcomes were analyzed. <b><i>Results:</i></b> One hundred and sixty-one patients were enrolled in this study. The 5-year overall (OS), disease-specific (DSS), disease-free (DFS), and laryngectomy-free survival rates were 84.5%, 97.9%, 79.2%, and 93.5%, respectively. The most common stage, histopathological type, and type of endoscopic cordectomy were T₁ stage, well-differentiated cancer, and type 2 cordectomy, respectively. A positive surgical margin was defined in 20 (12.4%) patients. There was a significant relationship between histopathological grade and positive surgical margins (<i>p</i> = 0.038). OS and DSS rates of “wait and see” modality were lower, while DFS of radiotherapy was lower than that of other treatment modalities in patients with positive surgical margins, but the differences were not statistically significant. Nineteen (11.8%) patients had a recurrence. DSS was statistically significantly lower in patients with recurrence (<i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> The results of our study showed that anterior commissure involvement, surgical margin positivity, and higher T stage statistically did not reduce survival rates in early-stage LSCC patients treated with _LTLM. As the histopathological grade of the tumor worsens, the risk of surgical margin positivity increases. RT may have a negative effect on recurrence and organ preservation in the additional treatment of patient with positive surgical margins.

Radiomics outperforms clinical factors in characterizing human papilloma virus (HPV) for patients with oropharyngeal squamous cell carcinomas

Purpose: To utilize radiomic features extracted from CT images to characterize Human Papilloma Virus (HPV) for patients with oropharyngeal cancer squamous cell carcinoma (OPSCC). Methods: One hundred twenty-eight OPSCC patients with known HPV-status (60-HPV+ and 68-HPV-, confirmed by immunohistochemistry-P16-protein testing) were retrospectively studied. Radiomic features (11 feature-categories) were extracted in 3D from contrast-enhanced (CE)-CT images of gross-tumor-volumes using ‘in-house’ software (‘ROdiomiX’) developed and validated following the image-biomarker-standardization-initiative (IBSI) guidelines. Six clinical factors were investigated: Age-at-Diagnosis, Gender, Total-Charlson, Alcohol-Use, Smoking-History, and T-Stage. A Least-Absolute-Shrinkage-and-Selection-Operation (Lasso) technique combined with a Generalized-Linear-Model (Lasso-GLM) were applied to perform regularization in the radiomic and clinical feature spaces to identify the ranking of optimal feature subsets with most representative information for prediction of HPV. Lasso-GLM models/classifiers based on clinical factors only, radiomics only, and combined clinical and radiomics (ensemble/integrated) were constructed using random-permutation-sampling. Tests of significance (One-way ANOVA), average Area-Under-Receiver-Operating-Characteristic (AUC), and Positive and Negative Predictive values (PPV and NPV) were computed to estimate the generalization-error and prediction performance of the classifiers. Results: Five clinical factors, including T-stage, smoking status, and age, and 14 radiomic features, including tumor morphology, and intensity contrast were found to be statistically significant discriminators between HPV positive and negative cohorts. Performances for prediction of HPV for the 3 classifiers were: Radiomics-Lasso-GLM: AUC/PPV/NPV=0.789/0.755/0.805; Clinical-Lasso-GLM: 0.676/0.747/0.672, and Integrated/Ensemble-Lasso-GLM: 0.895/0.874/0.844. Results imply that the radiomics-based classifier enabled better characterization and performance prediction of HPV relative to clinical factors, and that the combination of both radiomics and clinical factors yields even higher accuracy characterization and predictive performance. Conclusion: Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results in support of the role of radiomic features towards characterization of HPV in patients with OPSCC.