An Entire Renal Anatomy Extraction Network for Advanced CAD During Partial Nephrectomy

Partial nephrectomy (PN) is common surgery in urology. Digitization of renal anatomies brings much help to many computer-aided diagnosis (CAD) techniques during PN. However, the manual delineation of kidney vascular system and tumor on each slice is time consuming, error-prone, and inconsistent. Therefore, we proposed an entire renal anatomies extraction method from Computed Tomographic Angiographic (CTA) images fully based on deep learning. We adopted a coarse-to-fine workflow to extract target tissues: first, we roughly located the kidney region, and then cropped the kidney region for more detail extraction. The network we used in our workflow is based on 3D U-Net. To dealing with the imbalance of class contributions to loss, we combined the dice loss with focal loss, and added an extra weight to prevent excessive attention. We also improved the manual annotations of vessels by merging semi-trained model's prediction and original annotations under supervision. We performed several experiments to find the best-fitting combination of variables for training. We trained and evaluated the models on our 60 cases dataset with 3 different sources. The average dice score coefficient (DSC) of kidney, tumor, cyst, artery, and vein, were 90.9%, 90.0%, 89.2%, 80.1% and 82.2% respectively. Our modulate weight and hybrid strategy of loss function increased the average DSC of all tissues about 8-20%. Our optimization of vessel annotation improved the average DSC about 1-5%. We proved the efficiency of our network on renal anatomies segmentation. The high accuracy and fully automation make it possible to quickly digitize the personal renal anatomies, which greatly increases the feasibility and practicability of CAD application on urology surgery

USPs in Pancreatic Ductal Adenocarcinoma: A Comprehensive Bioinformatic Analysis of Expression, Prognostic Significance, and Immune Infiltration

Pancreatic ductal adenocarcinoma (PDAC), as an intractable malignancy, still causes an extremely high mortality worldwide. The ubiquitin-specific protease (USP) family constitutes the major part of deubiquitinating enzymes (DUBs) which has been reported to be involved in initiation and progression of various malignancies via the function of deubiquitination. However, the biological function and clinical values of USPs in PDAC have not been comprehensively elucidated. In this study, Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) datasets, UALCAN database, and the Human Protein Atlas (HPA) online tool were used to analyze the expression level and the relationship between USP expression and clinicopathological features in PDAC. Survival module of HPA and Kaplan-Meier plotter (KMP) databases was recruited to explore the prognostic value of USPs. Tumor Immune Estimation Resource (TIMER) online tool and KMP databases were utilized to elucidate tumor immune infiltration and immune-related survival of USPs. CBioPortal online tool was used to identify the gene mutation level of USPs in PDAC. Both cBioPortal and LinkedOmics were used to confirm the potential biological functions of USPs in PDAC. Our study showed that USP10, USP14, USP18, USP32, USP33, and USP39 (termed as six-USPs) expressions were significantly elevated in tumor tissues. The high expression of the four USPs (USP10, USP14, USP18, and USP39) indicated a poor prognosis. A significant relationship was indicated between the expression of six-USPs and clinicopathological features. Also, the expression of six-USPs was related to promoter methylation level. Moreover, more than 40% genetic alterations and mutations were discovered in six-USPs. Furthermore, the six-USP expression was correlated with immune infiltration and immune-related prognosis. The functional analysis found that the six-USPs were involved in various biological processes and signaling pathways, such as nucleocytoplasmic transport, choline metabolism in cancer, cell cycle, ErbB signaling pathway, RIG-I-like receptor signaling pathway, TGF-β signaling pathway, and TNF signaling pathway. In conclusion, the results showed that six-USPs are potential prognostic biomarkers and can be recruited as possible therapeutic targets of PDAC

High Expression of ITGA3 Promotes Proliferation and Cell Cycle Progression and Indicates Poor Prognosis in Intrahepatic Cholangiocarcinoma

Integrin subunit alpha 3 (ITGA3) interacts with a beta 1 subunit to form a member of the integrin family. Integrins are heterodimeric integral membrane proteins that serve as cell surface adhesion proteins. In this research, we investigated the biological function of this protein in human intrahepatic cholangiocarcinoma (ICC) for the first time. Here, using Western blotting and immunohistochemistry assays, we discovered that ITGA3 was overexpressed in ICC cell lines and ICC patients. Moreover, we found ITGA3 expression correlated with several clinicopathological features, including tumor size, lymph node metastasis, and the TNM stage. Patients with high ITGA3 expression underwent a worse prognosis after complete resection compared with patients with low ITGA3 expression in terms of overall survival. Furthermore, we demonstrated that ITGA3 could significantly promote ICC cell proliferation and cell cycle progression in vitro. However, as a classical cell surface adhesion molecule, we found ITGA3 correlated negatively with the migration and invasion of ICC cell lines, which differs from other malignant tumors. Generally, these findings suggest that ITGA3 may play a role as a potential oncogene in ICC and suppression of ITGA3 expression may establish a novel target for guiding the therapy of ICC patients

Expression and Clinical Significance of the Novel Long Noncoding RNA ZNF674-AS1 in Human Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) play crucial roles in cancer occurrence and progression. However, the relationship between the expression levels of lncRNAs and the hepatocellular carcinoma (HCC) process is unclear. The goal of this study was to determine the expression level of ZNF674-AS1, a newly found lncRNA, in HCC and its clinical association. The expression of ZNF674-AS1 in 137 pairs of tumorous and adjacent normal tissues from patients with HCC was detected by quantitative real-time reverse transcription polymerase chain reaction. Additionally, the potential associations between its level in HCC tissue and clinicopathological features were analyzed. The expression of ZNF674-AS1 in the HCC cell lines HepG2, HCCLM3, SK-Hep1, HuH7, Hep3B, and MHCC97H was significantly downregulated compared with that in the normal liver cell line QSG-7701. The expression of ZNF674-AS1 was downregulated in 72% (99/137) of HCC tissues compared with that in paired adjacent normal tissues (p<0.01). The results showed that the ZNF674-AS1 expression level was significantly correlated with metastasis (p=0.041), clinical stage (p=0.039), and histopathologic grading (p=0.045). In addition, the Kaplan–Meier survival curves revealed that low ZNF674-AS1 expression was associated with poor prognosis in patients with HCC. Our data suggest that ZNF674-AS1 may play some role during cancer occurrence and progression and may be a new biomarker for HCC

Identification of snoRNA SNORA71A as a Novel Biomarker in Prognosis of Hepatocellular Carcinoma

Background. Small nucleolar RNAs (snoRNAs) have been proved to play important roles in various cellular physiological process. Recently, dysregulation of snoRNA SNORA71A has been found involved in tumorigenesis of various malignant cancers. However, the emerging effects of SNORA71A in hepatocellular carcinoma (HCC) remain largely unclear. In this study, we aimed to explore the SNORA71A expression and its underlying significance in HCC. Methods. Expression of SNORA71A in cell lines and clinical specimens was measured by quantitative real-time PCR. Then, all enrolled HCC patients were divided into low and high SNORA71A expression subgroups and then they were compared in the aspects of clinical features as well as survival outcome by respective statistical analysis methods. Results. SNORA71A was significantly downexpressed in SK-HEP-1 (P=0.001), Huh-7 (P<0.001), Hep3B (P<0.001), and clinical HCC specimens (P=0.006). Comparing the clinical features between SNORA71A expression subgroups, it showed that low SNORA71A expression was significantly associated with large tumor diameter, multiple lesions, capsular invasion, bad tumor differentiation, and TNM stage (P<0.05). Furthermore, it was found that HCC patients with lower SNORA71A expression had higher risk in postoperative tumor relapse (median time: 9.5 vs. 35.2 months; low vs. high; P<0.001) and poor overall survival (median time: 36.8 vs. 52.9 months; low vs. high; P<0.001). Besides, SNORA71A expression served as independent risk factors for tumor-free (HR=0.450; 95% CI [0.263-0.770]; P=0.004) and long-term survival (HR=0.289; 95% CI [0.127-0.657]; P=0.003). Conclusions. Our study for the first time demonstrated that downregulation of SNORA71A could serve as a novel biomarker for clinical assessment and prognostic prediction of HCC patients

A Meta-Analysis of Randomized Controlled Trials of Low-Volume Polyethylene Glycol plus Ascorbic Acid versus Standard-Volume Polyethylene Glycol Solution as Bowel Preparations for Colonoscopy

<div><p>Background</p><p>Standard-volume polyethylene glycol (PEG) gut lavage solutions are safe and effective, but they require the consumption of large volumes of fluid. A new lower-volume solution of PEG plus ascorbic acid has been used recently as a preparation for colonoscopy.</p><p>Aim</p><p>A meta-analysis was performed to compare the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy.</p><p>Study</p><p>Electronic and manual searches were performed to identify randomized controlled trials (RCTs) that compared the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. After a methodological quality assessment and data extraction, the pooled estimates of bowel preparation efficacy during bowel cleansing, compliance with preparation, willingness to repeat the same preparation, and the side effects were calculated. We calculated pooled estimates of odds ratios (OR) by fixed- and/or random-effects models. We also assessed heterogeneity among studies and the publication bias.</p><p>Results</p><p>Eleven RCTs were identified for analysis. The pooled OR for preparation efficacy during bowel cleansing and for compliance with preparation for low-volume PEG plus ascorbic acid were 1.08 (95% CI = 0.98–1.28, P = 0.34) and 2.23 (95% CI = 1.67–2.98, P<0.00001), respectively, compared with those for standard-volume PEG. The side effects of vomiting and nausea for low-volume PEG plus ascorbic acid were reduced relative to standard-volume PEG. There was no significant publication bias, according to a funnel plot.</p><p>Conclusions</p><p>Low-volume PEG plus ascorbic acid gut lavage achieved non-inferior efficacy for bowel cleansing, is more acceptable to patients, and has fewer side effects than standard-volume PEG as a bowel preparation method for colonoscopy.</p></div