Cancers, Vol. 9, Pages 156: Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

Cancers, Vol. 9, Pages 156: Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

Cancers doi: 10.3390/cancers9110156

Authors: Megha Bhardwaj Vanessa Erben Petra Schrotz-King Hermann Brenner

Objective: In order to find low abundant proteins secretome and tumor tissue proteome data have been explored in the last few years for the diagnosis of colorectal cancer (CRC). In this review we aim to summarize the results of studies evaluating markers derived from the secretome and tumor proteome for blood based detection of colorectal cancer. Methods: Observing the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines PubMed and Web of Science databases were searched systematically for relevant studies published up to 18 July 2017. After screening for predefined eligibility criteria a total of 47 studies were identified. Information on diagnostic performance indicators, methodological procedures and validation was extracted. Functions of proteins were identified from the UniProt database and the the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess study quality. Results: Forty seven studies meeting inclusion criteria were identified. Overall, 83 different proteins were identified, with carcinoembryonic Antigen (CEA) being by far the most commonly reported (reported in 24 studies). Evaluation of the markers or marker combinations in blood samples from CRC cases and controls yielded apparently very promising diagnostic performances, with area under the curve >0.9 in several cases, but lack of internal or external validation, overoptimism due to overfitting and spectrum bias due to evaluation in clinical setting rather than screening settings are major concerns. Conclusions: Secretome and tumor proteome-based biomarkers when validated in blood yield promising candidates. However, for discovered protein markers to be clinically applicable as screening tool they have to be specific for early stages and need to be validated externally in larger studies with participants recruited in true screening setting.

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Cancers, Vol. 9, Pages 156: Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

Cancers, Vol. 9, Pages 156: Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

Cancers doi: 10.3390/cancers9110156

Authors: Megha Bhardwaj Vanessa Erben Petra Schrotz-King Hermann Brenner

Objective: In order to find low abundant proteins secretome and tumor tissue proteome data have been explored in the last few years for the diagnosis of colorectal cancer (CRC). In this review we aim to summarize the results of studies evaluating markers derived from the secretome and tumor proteome for blood based detection of colorectal cancer. Methods: Observing the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines PubMed and Web of Science databases were searched systematically for relevant studies published up to 18 July 2017. After screening for predefined eligibility criteria a total of 47 studies were identified. Information on diagnostic performance indicators, methodological procedures and validation was extracted. Functions of proteins were identified from the UniProt database and the the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess study quality. Results: Forty seven studies meeting inclusion criteria were identified. Overall, 83 different proteins were identified, with carcinoembryonic Antigen (CEA) being by far the most commonly reported (reported in 24 studies). Evaluation of the markers or marker combinations in blood samples from CRC cases and controls yielded apparently very promising diagnostic performances, with area under the curve >0.9 in several cases, but lack of internal or external validation, overoptimism due to overfitting and spectrum bias due to evaluation in clinical setting rather than screening settings are major concerns. Conclusions: Secretome and tumor proteome-based biomarkers when validated in blood yield promising candidates. However, for discovered protein markers to be clinically applicable as screening tool they have to be specific for early stages and need to be validated externally in larger studies with participants recruited in true screening setting.

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Acute appendicitis presenting as a complicated inguinal hernia: a case of left-sided Amyand’s hernia in an elderly man

Abstract

Amyand's hernia (AH) is characterized by the presence of the vermiform appendix in an inguinal hernia sac. Typically presenting on the right side and with manifestations similar to those seen in complicated hernias, it presents a diagnostic challenge and is frequently only diagnosed intraoperatively. We present the case of a left-sided AH on a 75-year-old man treated with appendicectomy, orchidectomy and hernioplasty without mesh.

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Colon adenocarcinoma after jejunoileal bypass for morbid obesity

Abstract

Jejunoileal bypass (JIB) was developed as a surgical treatment for morbid obesity in the early 1950s. However, this procedure is now known to be associated with multiple metabolic complications and has subsequently been abandoned as a viable bariatric procedure. Some of these known complications include renal stone formation, liver failure, migratory arthritis, fat-soluble deficiencies, blind-loop syndrome and severe diarrhea. Additionally, there have been animal models suggesting colon dysplasia after JIB. To our knowledge however, in humans, no colon cancers have been attributed to JIB in the literature. Here we report a 63-year-old morbidly obese female who had a JIB surgery in 1973 and subsequently was found to have numerous sessile colonic polyps throughout her colon and adenocarcinoma of the ascending colon without any family history of colonic polyposis syndromes or colon cancer.

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Repair of giant inguinoscrotal hernia with loss of domain

Abstract

A massive inguinoscrotal hernia extending below the midpoint of the inner thigh, in a standing position, constitute a 'giant' inguinoscrotal hernia. A 74-year-old male presented with giant left sided inguinal hernia for the last 30 years. Patient underwent open repair under general anesthesia after perioperative respiratory exercise. Standard hernia repair identified a sliding hernia containing entire omentum, small and large bowel, and the appendix. Giant hernias pose a challenging problem because reduction of the hernia contents inside the abdominal cavity may increase intra-abdominal and thoracic pressures. Recurrence remains an issue for these patients after successful meshoplasty and debulking of abdominal contents. We describe a simple reduction with biological mesh repair, omentectomy, small bowel resection and sigmoidopexy as a viable technique for patients with greater than 50% of abdominal contents in the inguinoscrotal region with complete loss of domain.

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Prognostic relevance of programmed cell death ligand 1 expression in glioblastoma

Abstract

The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation assay and fluorescence in situ hybridization (FISH) for the assessment of 1p/19q deletion were performed. Expression of PD-L1 in tumour cells and TIIs was found in 37 (32.2%) and 6 (5.2%) patients, respectively. Kaplan–Meier analysis indicated that PD-L1 expression in tumour cells was significantly associated with poor overall survival (OS) (P = 0.017), though multivariate Cox analysis did not confirm this association (hazard ratio 1.204; P = 0.615). PD-L1 expression in TIIs did not correlate with the patient prognosis (P = 0.545). In addition, MGMT methylation and IDH-1 (R132H) expression were associated with a better prognosis (P < 0.001 and P = 0.024, respectively). The expression of PD-L1 was associated with CD3-positive T-cell infiltration (P < 0.001), and IDH-1 wild type status (P = 0.008). A deeper insight into PD-L1 expression could help to ensure the success of future immunotherapy in GBM. Our study suggested that PD-L1 target therapy might be beneficial for PD-L1-expressing GBM patients with a poor prognosis.

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Efficacy and prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma

Abstract

The purpose of this study is to study the usefulness of post-remission antiviral therapy in cases of HCV-RNA-positive diffuse large-cell lymphoma. Antiviral therapy against HCV was performed after remission using CHOP or CHOP-like chemotherapy in combination with rituximab in five successive cases of HCV-RNA-positive diffuse large-cell lymphoma. The control groups consisted of a group of HCV-RNA-positive diffuse large-cell lymphoma cases prior to this trial (control 1), and a group of cases that tested negative for HIV, HCV, and HBV (control 2). All the cases were in remission at the time of initial treatment. There were no significant differences between the three groups in terms of age, sex, treatment, stage, or International Prognosis Index (IPI). When HCV antiviral therapy was performed after treatment for diffuse large-cell lymphoma, we observed no recurrence or deaths, and the 2-year overall survival and progression-free survival rates were significantly greater than those in the control 1 group (P = 0.0246). It is possible that a better prognosis can be achieved by performing HCV antiviral therapy after achieving remission in cases of HCV-RNA-positive diffuse large-cell lymphoma through the use of R-CHOP or similar treatments.

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