RT @AlvaroKohn : Very interesting personalized cancer care symposium @Oslounivsykehus https://t.co/SXV1jE7uXg

RT @AlvaroKohn : Very interesting personalized cancer care symposium @Oslounivsykehus https://t.co/SXV1jE7uXg

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://twitter.com/ecancer/status/712585633433317376
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‘Silencer molecules’ switch off cancer’s ability to spread around body https://t.co/SeGbuV1e4S https://t.co/PWQwNLDlPB

‘Silencer molecules’ switch off cancer’s ability to spread around body https://t.co/SeGbuV1e4S https://t.co/PWQwNLDlPB

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://twitter.com/ecancer/status/712580283422343169
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RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy

Abstract

Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway, however no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival (RFS) were estimated by the Kaplan-Meier method and the log-rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow up of 84.1 months (57.2–NA) for a survivor, the 4-year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild-type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and RFS.

RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival. This article is protected by copyright. All rights reserved.

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Epidemiologic evidence of slow growing, non-progressive or regressive breast cancer: a systematic review

Abstract

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC.

PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis.

Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In 3 controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19%-43%.

Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2%-14.7%.

Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared to non-screened BC was estimated as 1.2 and 1.1.

It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies. This article is protected by copyright. All rights reserved.

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Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

Abstract

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC-US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n=3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n=9,405) or Linear Array HPV-Genotyping test (LA) (n=1,533). Women with ≥1 subsequent examination in the register (n=13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8%–89.6%] versus 59.3% [95% CI: 58.1%–60.4%]) and higher positive predictive value (PPV) (38.2% [95% confidence interval [CI]: 33.8%–43.1%] versus 19.5% [95% CI: 17.8%–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3%–74.5%] versus 97.0% [95% CI: 95.5%–98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2%–4.2%] versus 0.5% [95% CI: 0.3%–0.7%]). Patterns were similar after 18 months and 5 years' follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test. This article is protected by copyright. All rights reserved.

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Use of thermo-coagulation as an alternative treatment modality in a ‘screen and treat' programme of cervical screening in rural Malawi

Abstract

The incidence of cervical cancer in Malawi is the highest in the world and projected to increase in the absence of interventions. Although Government policy supports screening using visual inspection with acetic acid (VIA), screening provision is limited due to lack of infrastructure, trained personnel, cost and availability of gas for cryotherapy. Recently, thermo-coagulation has been acknowledged as a safe and acceptable procedure suitable for low–resource settings. We introduced thermo-coagulation for treatment of VIA positive lesions as an alternative to cryotherapy within a cervical screening service based on VIA, coupled with appropriate, sustainable pathways of care for women with high grade lesions and cancers. Detailed planning was undertaken for VIA clinics, approvals were obtained from the Ministry of Health, and Regional and Village Chiefs. Educational resources were developed. Thermo-coagulators were introduced into hospital and health centre settings, with theoretical and practical training in safe use and maintenance of equipment. 7088 previously unscreened women attended VIA clinics between October 2013 and March 2015. Screening clinics were held daily in the hospital and weekly in the health centres. Overall VIA positivity was 6.1%. Almost 90% received same day treatment in the hospital setting, and 3-6 month cure rates of over 90% are observed. Thermo-coagulation proved feasible and acceptable in this setting. Effective implementation requires comprehensive training and provider support, ongoing competency assessment, quality assurance and improvement audit. Thermo-coagulation offers an effective alternative to cryotherapy and encouraged VIA screening of many more women. This article is protected by copyright. All rights reserved.

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Preferential Tumor Cellular Uptake and Retention of Indocyanine Green for In Vivo Tumor Imaging

Abstract

Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor-cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. This article is protected by copyright. All rights reserved.

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