Cost analysis of single-incision versus conventional laparoscopic surgery for colon cancer: A propensity score-matching analysis

BACKGROUND/OBJECTIVE: Although many studies have demonstrated similar perioperative outcomes for single-incision laparoscopic surgery (SILS) and conventional laparoscopic surgery (CLS) for colon cancer, few have directly compared the costs of them. We aimed to compare costs between SILS and CLS for colon cancer. METHODS: We analyzed the clinical outcomes and overall hospital costs of patients who underwent laparoscopic surgery for colon cancer from July 2009 to September 2014 at our institution; 288 were used for analysis after propensity score matching. The total hospital charge, including fees for the operation, anesthesia, preoperative diagnosis, and postoperative management was analyzed. RESULTS: The total hospital charges were similar in both groups ($8770.40 vs.$8352.80, P = 0.099). However, the patients' total hospital bill was higher in the SILS group than in the CLS group ($4184.82 vs.$3735.00, P < 0.001) mainly due to the difference of the cost of access devices. There was no difference in the additional costs associated with readmission due to late complications between the two groups ($2383.08 vs.$2288.33, P = 0.662). Incremental cost-effectiveness ratio for total incision length in 'total hospital charge' and patient's bill and government's bill in 'cost of instruments and supplies' were -$107.08/1 cm, -$109.70/1 cm, and $80.64/1 cm, respectively. CONCLUSION: SILS for colon cancer yielded similar costs as well as perioperative and long-term outcomes compared with CLS. Therefore, SILS can be considered a reasonable treatment option for colon cancer for selective patients.ope

Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

Background: Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods: All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer's protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer's instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion: This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1 .ope

Droplet digital PCR-based EGFR mutation detection with an internal quality control index to determine the quality of DNA.

In clinical translational research and molecular in vitro diagnostics, a major challenge in the detection of genetic mutations is overcoming artefactual results caused by the low-quality of formalin-fixed paraffin-embedded tissue (FFPET)-derived DNA (FFPET-DNA). Here, we propose the use of an 'internal quality control (iQC) index' as a criterion for judging the minimum quality of DNA for PCR-based analyses. In a pre-clinical study comparing the results from droplet digital PCR-based EGFR mutation test (ddEGFR test) and qPCR-based EGFR mutation test (cobas EGFR test), iQC index ≥ 0.5 (iQC copies ≥ 500, using 3.3 ng of FFPET-DNA [1,000 genome equivalents]) was established, indicating that more than half of the input DNA was amplifiable. Using this criterion, we conducted a retrospective comparative clinical study of the ddEGFR and cobas EGFR tests for the detection of EGFR mutations in non-small cell lung cancer (NSCLC) FFPET-DNA samples. Compared with the cobas EGFR test, the ddEGFR test exhibited superior analytical performance and equivalent or higher clinical performance. Furthermore, iQC index is a reliable indicator of the quality of FFPET-DNA and could be used to prevent incorrect diagnoses arising from low-quality samples.ope

Niclosamide reverses adipocyte induced epithelial-mesenchymal transition in breast cancer cells via suppression of the interleukin-6/STAT3 signalling axis

The microenvironment of breast cancer comprises predominantly of adipocytes. Adipocytes drive cancer progression through the secretion adipocytokines. Adipocytes induce epithelial mesenchymal transition of breast cancer cells through paracrine IL-6/Stat3 signalling. Treatment approaches that can target adipocytes in the microenvironment and abrogate paracrine signals that drive breast cancer growth and metastasis are urgently needed. Repositioning of old drugs has become an effective approach for discovering new cancer drugs. In this study, niclosamide, an FDA approved anthelminthic drug was evaluated for its anti-breast cancer activity and its ability to inhibit adipocytes induced EMT. Niclosamide potently inhibited proliferation, migration and invasion at low concentration and induced significant apoptosis at high concentrations in human breast cancer cell lines MDA-MB-468 and MCF-7. Additionally, niclosamide reversed adipocyte-induced EMT with a correlated inhibition of IL-6/Stat3 activation and downregulation of EMT-TFs TWIST and SNAIL. Moreover, niclosamide markedly impaired MDA-MB-468 and MCF-7 migration and invasion. We further found that the inhibitory effects of niclosamide on MDA-MB-468 and MCF-7 motility was closely related to destabilization of focal adhesion complex formation. With decreased co-localization of focal adhesion kinase (FAK) and phosphorylated paxillin (pPAX). Collectively, these results demonstrate that niclosamide could be used to inhibit adipocyte-induced breast cancer growth and metastasis.ope

Associations between gene expression profiles of invasive breast cancer and Breast Imaging Reporting and Data System MRI lexicon

PURPOSE: To evaluate whether the Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon could reflect the genomic information of breast cancers and to suggest intuitive imaging features as biomarkers. METHODS: Matched breast MRI data from The Cancer Imaging Archive and gene expression profile from The Cancer Genome Atlas of 70 invasive breast cancers were analyzed. Magnetic resonance images were reviewed according to the BI-RADS MRI lexicon of mass morphology. The cancers were divided into 2 groups of gene clustering by gene set enrichment an alysis. Clinicopathologic and imaging characteristics were compared between the 2 groups. RESULTS: The luminal subtype was predominant in the group 1 gene set and the triple-negative subtype was predominant in the group 2 gene set (55 of 56, 98.2% vs. 9 of 14, 64.3%). Internal enhancement descriptors were different between the 2 groups; heterogeneity was most frequent in group 1 (27 of 56, 48.2%) and rim enhancement was dominant in group 2 (10 of 14, 71.4%). In group 1, the gene sets related to mammary gland development were overexpressed whereas the gene sets related to mitotic cell division were overexpressed in group 2. CONCLUSION: We identified intuitive imaging features of breast MRI associated with distinct gene expression profiles using the standard imaging variables of BI-RADS. The internal enhancement pattern on MRI might reflect specific gene expression profiles of breast cancers, which can be recognized by visual distinction.ope

A novel long noncoding RNA Linc-ASEN represses cellular senescence through multileveled reduction of p21 expression

Long noncoding RNAs (lncRNAs) regulating diverse cellular processes implicate in many diseases. However, the function of lncRNAs in cellular senescence remains largely unknown. Here we identify a novel long intergenic noncoding RNA Linc-ASEN expresses in prematurely senescent cells. We find that Linc-ASEN associates with UPF1 by RNA pulldown mass spectrometry analysis, and represses cellular senescence by reducing p21 production transcriptionally and posttranscriptionally. Mechanistically, the Linc-ASEN-UPF1 complex suppressed p21 transcription by recruiting Polycomb Repressive Complex 1 (PRC1) and PRC2 to the p21 locus, and thereby preventing binding of the transcriptional activator p53 on the p21 promoter through histone modification. In addition, the Linc-ASEN-UPF1 complex repressed p21 expression posttranscriptionally by enhancing p21 mRNA decay in association with DCP1A. Accordingly, Linc-ASEN levels were found to correlate inversely with p21 mRNA levels in tumors from patient-derived mouse xenograft, in various human cancer tissues, and in aged mice tissues. Our results reveal that Linc-ASEN prevents cellular senescence by reducing the transcription and stability of p21 mRNA in concert with UPF1, and suggest that Linc-ASEN might be a potential therapeutic target in processes influenced by senescence, including cancer.ope

AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation. Then, AIMP2-DX2 competitively blocks the access of Smurf2 (SMAD Ubiquitination Regulatory Factor 2) to KRAS, thus preventing ubiquitin-mediated degradation. Moreover, AIMP2-DX2 levels are positively correlated with KRAS levels in colon and lung cancer cell lines and tissues. We also identified a small molecule that specifically bound to the KRAS-binding region of AIMP2-DX2 and inhibited the interaction between these two factors. Treatment with this compound reduces the cellular levels of KRAS, leading to the suppression of KRAS-dependent cancer cell growth in vitro and in vivo. These results suggest the interface of AIMP2-DX2 and KRAS as a route to control KRAS-driven cancers.ope

A Granular Cell Tumor of the Rectum: A Case Report and Review of the Literature

A granular cell tumor (GCT) is an uncommon mesenchymal lesion that rarely occurs in the colon and the rectum. We describe the case of 51-year-old man with a 2-cm-sized rectal GCT 10 cm above the anal verge that was incidentally detected after a screening colonoscopy. Preoperative radiologic studies demonstrated a suspicious submucosal rectal mass with mesorectal fat infiltration, but without circumferential resection margin threatening, extramural vessel invasion, and regional lymph-node enlargement. The tumor was resected by using a transanal endoscopic operation (TEO) without immediate postoperative complications. The final pathology revealed that the tumor consisted of a GCT that had invaded the subserosa with clear margins. It had no other risk factors for malignancy according to Fanburg-Smith criteria. We systematically reviewed the English literature by using PubMed and Google Scholar. This report may be the first documented case in the literature to describe a TEO for a GCT that had invaded the subserosa in the rectum.ope

Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling

The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.ope

IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours

During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these advanced tumours. During this process, we find that the co-expression of Tim-3 and PD-1 marks functionally exhausted NK cells in advanced tumours and that MHC-I downregulation in tumours is closely associated with the induction of NK-cell exhaustion in both tumour-bearing mice and cancer patients. Furthermore, the recovery of NK-cell function by IL-21 is critical for the anti-tumour effects of the vaccine against advanced tumours. These results reveal the process involved in the induction of NK-cell dysfunction in advanced cancers and provide a guidance for the development of strategies for cancer immunotherapy.ope