Cancer by Sfakianakis Alexandros: 03/21/18

Τετάρτη 21 Μαρτίου 2018

Irinotecan-associated dysarthria: A single institution case series with management implications in patients with gastrointestinal malignancies

Journal of Oncology Pharmacy Practice, Ahead of Print.

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Journal of Oncology Pharmacy Practice, Ahead of Print.

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Isavuconazole therapy in an FLT3 mutated acute myeloid leukemia patient receiving midostaurin: A case report

Journal of Oncology Pharmacy Practice, Ahead of Print.

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Fatty acid receptor GPR120: a novel marker for human melanoma

The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of G-protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long-chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma metastasis (n=43) were immunohistochemically stained against GPR120. The staining was evaluated by three trained dermatopathologists and independently scored. Compared with nevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120 expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0–10], whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS score: 7, range: 0–12) and in melanoma metastasis 27 out of 43 were highly GPR120-positive (median IRS score: 9, range: 0–12). GPR120 expression and tumor thickness (mm) show a statistically significant correlation in primary melanoma (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis and in sebaceous and sweat glands, which is yet not described. This study identified GPR120 as a novel marker for melanoma, indicating that melanoma cells are sensitive to free fatty acids. It is tempting to speculate that pharmacologically interfering with GPR120 signaling might improve melanoma therapy. Correspondence to Dr Johannes Kleemann, Department of Dermatology, Venereology and Allergy, University Hospital Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany Tel: +49 696 301 5343; fax: +49 696 301 6466; e-mail: johannes.kleemann@kgu.de Received October 23, 2017 Accepted February 13, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Telomerase reverse transcriptase promoter mutations and solar elastosis in cutaneous melanoma

The aims of this study were to assess the prognostic potential of solar elastosis grading and telomerase reverse transcriptase (TERT) promoter mutations (TERTpmut) in melanoma and to evaluate whether an association between solar elastosis and TERTpmut exists. Solar elastosis in the dermis was evaluated in hematoxylin and eosin-stained whole slides from 486 malignant melanomas. Pyrosequencing was used to detect TERTpmut in 189 samples. There was no association between solar elastosis and TERTpmut (P=0.3). Severe elastosis was associated with older age (P

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Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications

Publication date: Available online 21 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Simona Camorani, Elvira Crescenzi, Monica Fedele, Laura Cerchia
Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies.In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers.

Graphical abstract

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Anti-hTERT siRNA-loaded nanoparticles block the growth of anaplastic thyroid cancer xenograft

The high frequency of hTERT-promoting mutations and the increased expression of hTERT mRNA in anaplastic thyroid cancer (ATC) make TERT a suitable molecular target for the treatment of this lethal neoplasm. In this study, we encapsulated an anti-hTERT oligonucleotide in biocompatible nanoparticles and analyzed the effects of this novel pharmaceutical preparation in preclinical models of ATC. Biocompatible nanoparticles were obtained in an acidified aqueous solution containing chitosan, anti-hTERT oligoRNAs and poloxamer 188 as a stabilizer. The effects of these anti-hTERT -nanoparticles (Na-siTERT) were tested in vitro on ATC cell lines (CAL-62 and 8505C) and in vivo on xenograft tumors obtained by flank injection of CAL-62 cells into SCID-mice. The Na-siTERT reduced the viability and migration of CAL-62 and 8505C cells after 48 h incubation. Intra-venous administration (every 48 h for 13 days) of this encapsulated drug in mice hosting a xenograft thyroid cancer determined a great reduction in the growth of the neoplasm (about 50% vs untreated animals or mice receiving empty nanoparticles), and decreased levels of Ki67 associated with lower hTERT expression. Moreover, the treatment resulted in minimal invasion of near-by tissues and reduced the vascularity of the xenograft tumor. No signs of toxicity appeared following this treatment. Telomere length was not modified by the Na-siTERT, indicating that the inhibitory effects of neoplasm growth was independent from the enzymatic telomerase function. These findings demonstrate the potential suitability of this anti-TERT nanoparticle formulation as a novel tool for ATC treatment.

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Anti-hTERT siRNA-loaded nanoparticles block the growth of anaplastic thyroid cancer xenograft

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In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics, Published online: 22 March 2018; doi:10.1038/s41416-018-0034-9

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

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Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037, Published online: 22 March 2018; doi:10.1038/s41416-018-0047-4

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

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A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma, Published online: 22 March 2018; doi:10.1038/s41416-018-0051-8

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

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The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma, Published online: 22 March 2018; doi:10.1038/s41416-018-0054-5

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

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Comment on ‘Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study’

Comment on 'Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study'

Comment on 'Clinical significance of <i>BRAF</i> non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study', Published online: 22 March 2018; doi:10.1038/s41416-018-0012-2

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer, Published online: 22 March 2018; doi:10.1038/s41416-018-0055-4

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

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Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics, Published online: 22 March 2018; doi:10.1038/s41416-018-0034-9

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

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Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037, Published online: 22 March 2018; doi:10.1038/s41416-018-0047-4

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

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A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

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Comment on ‘Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study’

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer, Published online: 22 March 2018; doi:10.1038/s41416-018-0055-4

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

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Chimeric Antigen Receptor T Cell-Mediated Neurotoxicity in Non-Human Primates [Research Articles]

Chimeric Antigen Receptor (CAR) T cell immunotherapy has revolutionised the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (CRS) and neurotoxicity. A major barrier to developing therapeutics to prevent CAR T cell-mediated neurotoxicity is the lack of clinically relevant models. Accordingly, we developed a rhesus macaque (RM) model of neurotoxicity via adoptive transfer of autologous CD20-specific CAR T cells. Following cyclophosphamide lymphodepletion, CD20 CAR T cells expand to 272-4450 cells/µl after 7-8 days and elicit CRS and neurotoxicity. Toxicities are associated with elevated serum IL-6, IL-8, IL-1RA, MIG and I-TAC levels, and disproportionately high cerebrospinal fluid (CSF) IL-6, IL-2, GM-CSF and VEGF levels. During neurotoxicity, both CD20 CAR and non-CAR T cells accumulate in the CSF and in the brain parenchyma. This RM model demonstrates that CAR T cell-mediated neurotoxicity is associated with pro-inflammatory CSF cytokines and a pan-T cell encephalitis.

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Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-cell Targets in Human IDH-Mutant Glioma

Purpose: Successful immunotherapies for IDH mut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. Experimental Design: Protein fractionations of tissue lysates from IDH mut gliomas (n=4) were performed. Fractions were tested by IFN-E; ELISpot assay for recognition through patient's T-cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico-predicted synthetic long-peptides in patients of origin, additional IDH mut glioma patients (n=16), and healthy donors (n=13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDH mut glioma stem-like cells (GSCs). HLA-A*02-restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T-cells by HLA-peptide tetramer analysis. Results: 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process 79 proteins were selected as potential T-cell antigens. 26 of these were recognized by the patients' T-cells and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDH mut glioma patients. Most immunogenic tumor-associated antigens (TAAs) were expressed in IDH mut gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02-restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T-cells in IDH mut glioma patients. Conclusion: By analyzing the repertoire of T-cell target antigens in IDH mut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDH mut tumors and GSCs.

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Induction of Telomere Dysfunction Prolongs Disease Control of Therapy-Resistant Melanoma

Purpose: Telomerase promoter mutations are highly prevalent in human tumors including melanoma. A subset of patients with metastatic melanoma often fail multiple therapies and there is an unmet and urgent need to prolong disease control for those patients. Experimental Design: Numerous pre-clinical therapy-resistant models of human and mouse melanoma were used to test the efficacy of a telomerase-directed nucleoside, 6-thio-2'-deoxyguanosine (6-thio-dG). Integrated transcriptomics and proteomics approaches were used to identify genes and proteins that were significantly down-regulated by 6-thio-dG. Results: We demonstrated the superior efficacy of 6-thio-dG both in vitro and in vivo that results in telomere dysfunction, leading to apoptosis and cell death in various pre-clinical models of therapy-resistant melanoma cells. 6-thio-dG concomitantly induces telomere dysfunction and inhibits the expression level of AXL. Conclusions: In summary, this study shows that indirectly targeting aberrant telomerase in melanoma cells with 6-thio-dG is a viable therapeutic approach in prolonging disease control and overcoming therapy resistance.

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A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy

Purpose: We established a computed tomography (CT)-derived approach to achieve accurate progression-free survival (PFS) prediction to EGFR tyrosine kinase inhibitors (TKIs) therapy in multicenter, stage IV EGFR-mutated non-small-cell lung cancer (NSCLC) patients. Experimental Design: 1032 CT-based phenotypic characteristics were extracted according to the intensity, shape and texture of NSCLC pre-therapy images. Based on these CT features extracted from 117 stage IV EGFR-mutant NSCLC patients, a CT-based phenotypic signature was proposed using a Cox regression model with LASSO penalty for the survival risk stratification of EGFR-TKI therapy. The signature was validated using two independent cohorts (101 and 96 patients, respectively). The benefit of EGFR-TKIs in stratified patients was then compared with another stage-IV EGFR-mutant NSCLC cohort only treated with standard chemotherapy (56 patients). Furthermore, an individualized prediction model incorporating the phenotypic signature and clinicopathologic risk characteristics was proposed for PFS prediction, and also validated by multicenter cohorts. Results: The signature consisted of 12 CT features demonstrated good accuracy for discriminating patients with rapid- and slow-progression to EGFR-TKI therapy in three cohorts (hazard ratio: 3.61, 3.77 and 3.67, respectively). Rapid-progression patients received EGFR TKIs did not show significant difference with patients underwent chemotherapy for progression-free survival benefit (p = 0.682). Decision curve analysis revealed that the proposed model significantly improved the clinical benefit compared with the clinicopathologic-based characteristics model (p < 0.0001). Conclusions:The proposed CT-based predictive strategy can achieve individualized prediction of PFS probability to EGFR-TKI therapy in NSCLCs, which holds promise of improving the pre-therapy personalized management of TKIs.

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The pattern of Mesenchymal stem cell expression is an independent marker of outcome in multiple myeloma.

Purpose: Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM. Experimental Design: To determine the impact of MSCs on MM outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in PCs or other cells present in BM aspirates. We then applied this MSC gene signature to whole BM biopsies of MM patients compared to healthy controls and determined MSC expression scores specific to MM and predictive of outcome. Results: We show that MM MSC gene expression signatures are able to differentiate MM from monoclonal gammopathy (MGUS) and smoldering MM (SMM) as well as from healthy controls and treated MM patients that have achieved a complete remission (CR). We identified a prognostic gene score based on three MSC specific genes COL4A1, NPR3 and ITGBL1, that was able to predict progression free survival (PFS) in MM patients and progression into MM from SMM. Conclusions: Our findings show that progression of MM and of SMM into MM not solely relies on intrinsic PC factors, but is independently impacted by the biology of the surrounding microenvironment.

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Ensartinib (X-396) in ALK-positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study

Purpose:Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC). Experimental Design: In dose escalation, ensartinib was administered at doses of 25–250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced ALK-positive NSCLC were administered 225 mg once daily. Patients who had received prior ALK TKI(s) and patients with brain metastases were allowed. Results: Thirty-seven patients enrolled in dose escalation, and 60 enrolled in dose expansion. The most common treatment-related toxicities were rash (56%), nausea (36%), pruritus (28%), vomiting (26%), and fatigue (22%); 23% of patients experienced a treatment-related Grade 3-4 toxicity (primarily rash and pruritus). The maximum tolerated dose was not reached, but the RP2D was chosen as 225 mg based on the frequency of rash observed at 250 mg without improvement in activity. Among the ALK-positive efficacy evaluable patients treated at ≥200 mg, the response rate (RR) was 60% and median progression-free survival (PFS) was 9.2 months. RR in ALK TKI naïve patients was 80% and median PFS was 26.2 months. In patients with prior crizotinib only, the RR was 69% and median PFS was 9.0 months. Responses were also observed in the central nervous system, with an intracranial RR of 64%. Conclusions: Ensartinib was active and generally well tolerated in patients with ALK-positive NSCLC.

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Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-cell Targets in Human IDH-Mutant Glioma

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Induction of Telomere Dysfunction Prolongs Disease Control of Therapy-Resistant Melanoma

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A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy

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The pattern of Mesenchymal stem cell expression is an independent marker of outcome in multiple myeloma.

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Ensartinib (X-396) in ALK-positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study

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Long non-coding RNA CASC2 inhibits tumorigenesis via the miR-181a/PLXNC1 axis in melanoma

Abstract

Melanoma is the most malignant and aggressive form of skin carcinoma originating in the pigment-producing melanocytes. In this study, to further investigate the molecular mechanisms of the development and progression of melanoma, we explored the impacts of long non-coding RNA (lncRNA) CASC2 on melanoma cell functions. Microarray analysis was carried out to identify the expression of lncRNA CASC2 in melanoma cells. MiR-181a was predicted as a sponging target of CASC2 by miRcode, while the 3′-UTR of Plexin C1 (PLXNC1) was a potential target of miR-181a according to the TargetScan database. The correlation among CASC2, miR-181a, and PLXNC1 was verified by dual luciferase reporter assay and qRT-PCR. After manipulation of CASC2, miR-181a and PLXNC1 expression with transfection in A375 and M14 cells, cell viability, apoptosis, and invasive ability were evaluated using CCK-8, flow cytometry and Transwell assays, respectively. A low expression of CASC2 was detected in melanoma tissues and cells. Dual luciferase reporting assay confirmed that miR-181a targeted the 3′-UTR of PLXNC1. Furthermore, CASC2 could efficiently sponge miR-181a, thereby facilitating the expression of PLXNC1. Up-regulation of CASC2 suppressed the cell proliferation and invasion, but induced the apoptosis of melanoma cells. Our results demonstrated that lncRNA CASC2 can promote PLXNC1 expression by sponging miR-181a, thereby inhibiting the proliferation and invasion of melanoma cells, indicating that lncRNA CASC2 functions via the miR-181a/PLXNC1 axis in melanoma.

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Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer patients: A prospective service development analysis

Publication date: Available online 21 March 2018
Source:Practical Radiation Oncology
Author(s): Sanjoy Chatterjee, Santam Chakraborty, Arunsingh Moses, Chandran Nallathambi, Anurupa Mahata, Samar Mandal, Rimpa Basu Achari, Indranil Mallick, Raj Kumar Shrimali, Tapesh Bhattacharyya, Sanjit Agrawal, Joydeep Ghosh, Rosina Ahmed
IntroductionUse of Deep Inspiration Breath Hold (DIBH) radiotherapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers.MethodsData regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiotherapy were compiled prospectively for all personnel (regarding person-hours, PH). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared to the DIBH plan. Mortality reduction due to use of DIBH was calculated using the years of life lost (YLLs) due to Ischemic Heart Disease (IHD) for Indians and the postulated reduction in risk of major cardiac events due to reduced cardiac dose.ResultsThe median reduction in mean heart dose (MHD) between the DIBH and FB plans was 166.7cGy (IQR: 62.7–257.4cGy). An extra 6.76 PH was required when implementing DIBH as compared to FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess YLLs due to IHD if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left sided breast cancers at 2.3 times the annual per-capita GDP.ConclusionAlthough routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

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Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer patients: A prospective service development analysis

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

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A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

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Comment on ‘Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study’

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The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

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In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

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Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

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A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

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Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

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Comment on ‘Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study’

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The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

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In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

http://ift.tt/2puihck

Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

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Cancers, Vol. 10, Pages 88: Use of the Ion PGM and the GeneReader NGS Systems in Daily Routine Practice for Advanced Lung Adenocarcinoma Patients: A Practical Point of View Reporting a Comparative Study and Assessment of 90 Patients

Cancers, Vol. 10, Pages 88: Use of the Ion PGM and the GeneReader NGS Systems in Daily Routine Practice for Advanced Lung Adenocarcinoma Patients: A Practical Point of View Reporting a Comparative Study and Assessment of 90 Patients

Cancers doi: 10.3390/cancers10040088

Authors: Simon Heeke Véronique Hofman Elodie Long-Mira Virginie Lespinet Salomé Lalvée Olivier Bordone Camille Ribeyre Virginie Tanga Jonathan Benzaquen Sylvie Leroy Charlotte Cohen Jérôme Mouroux Charles Marquette Marius Ilié Paul Hofman

Background: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform. Methods: Clinical samples from 90 patients (60 Retrospectively and 30 Prospectively) with lung adenocarcinoma were sequenced with both systems. Mutations were analyzed and EGFR, KRAS, BRAF, NRAS, ALK, PIK3CA and ERBB2 genes were compared and sampling time and suitability for clinical testing were assessed. Results: Both sequencing systems showed perfect concordance for the overlapping genes. Correlation of allele frequency was r2 = 0.93 for the retrospective patients and r2 = 0.81 for the prospective patients. Hands-on time and total run time were shorter using the PGM system, while the GeneReader platform provided good traceability and up-to-date interpretation of the results. Conclusion: We demonstrated the suitability of the GeneReader NGS system in routine practice in a clinical pathology laboratory setting.

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Cancers, Vol. 10, Pages 88: Use of the Ion PGM and the GeneReader NGS Systems in Daily Routine Practice for Advanced Lung Adenocarcinoma Patients: A Practical Point of View Reporting a Comparative Study and Assessment of 90 Patients

Cancers doi: 10.3390/cancers10040088

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Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma

Abstract

Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, has been increasingly associated with head and neck squamous cell carcinoma. The treatment of HPV-positive squamous cell carcinoma has a better response to both radiotherapy and chemotherapy and presents a better prognosis for the patient. Defining the underlying mechanism of the difference might help in developing future treatment options and could be an important factor in personal therapy planning. Endogenously secreted acid sphingomyelinase (ASMase) levels in the cellular stress caused by irradiation and cisplatin were investigated. MTT assay was performed to evaluate the viability of the treated cells. Keratinocytes were used to evaluate the effects of radiation on normal tissues. Irradiation caused a dose-dependent increase in ASMase activity in both SCC9 HPV-negative, and UDSCC2 HPV-positive cells. ASMase activity in UDSCC2 cells was significantly higher than that in SCC9 cells. UDSCC cells were more sensitive to cisplatin treatment than SCC cells, and the dose–response in the activity was observed in long-time treatments when high doses of cisplatin were used. The results of the current study have clearly showed that HPV positivity should be considered as one of the determinative factors which should be considered when tumor treatments are planned. However, further studies are needed to determine the differences in cellular responses and pathways among HPV-negative and HPV-positive cells.

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Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma

Abstract

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Impact of oral potentially malignant disorders on quality of life: a systematic review

Future Oncology, Ahead of Print.

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Diet and health—finding a path to Veritas

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Impact of oral potentially malignant disorders on quality of life: a systematic review

Future Oncology, Ahead of Print.

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Diet and health—finding a path to Veritas

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Diet and health—finding a path to Veritas

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Cancers, Vol. 10, Pages 87: Study of the Influence of NanOx Parameters

Cancers, Vol. 10, Pages 87: Study of the Influence of NanOx Parameters

Cancers doi: 10.3390/cancers10040087

Authors: Caterina Monini Micaela Cunha Etienne Testa Michaёl Beuve

NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and diffusion of reactive chemical species. In order to further characterize the new framework, we discuss the meaning and relevance of most of the NanOx parameters by evaluating their influence on the linear-quadratic coefficient α and on the dose deposited to achieve 10% or 1% of cell survival, D 10 % or D 1 % , as a function of LET. We perform a theoretical study in which variations in the input parameters are propagated into the model predictions for HSG, V79 and CHO-K1 cells irradiated by monoenergetic protons and carbon ions. We conclude that, in the current version of NanOx, the modeling of a specific cell line relies on five parameters, which have to be adjusted to several experimental measurements: the average cellular nuclear radius, the linear-quadratic coefficients describing photon irradiations and the α values associated with two carbon ions of intermediate and high-LET values. This may have interesting implications toward a clinical application of the new biophysical model.

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Effectiveness of urine fibronectin as a non-invasive diagnostic biomarker in bladder cancer patients: a systematic review and meta-analysis

Abstract

Background

Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection.

Methods

A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis.

Results

Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77–0.83), 0.79 (95%CI = 0.73–0.84), and 15.18 (95%CI = 10.07–22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79–0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82–0.90) and 0.89 (95%CI = 0.86–0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis.

Conclusions

Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.

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Cancers, Vol. 10, Pages 87: Study of the Influence of NanOx Parameters

Cancers, Vol. 10, Pages 87: Study of the Influence of NanOx Parameters

Cancers doi: 10.3390/cancers10040087

Authors: Caterina Monini Micaela Cunha Etienne Testa Michaёl Beuve

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Effectiveness of urine fibronectin as a non-invasive diagnostic biomarker in bladder cancer patients: a systematic review and meta-analysis

Abstract

Background

Methods

Results

Conclusions

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Tumor-infiltrating mast cells predict prognosis and gemcitabine-based adjuvant chemotherapeutic benefit in biliary tract cancer patients

Abstract

Background

Recent studies have reported TIMs play an important role in tumors progression or regression, but the effect of TIMs in biliary tract cancer remains unclear. The aim of this study is to investigate the prognostic value of tumor infiltrating mast cells (TIMs) and its influence on gemcitabine-based adjuvant chemotherapy (ACT) benefits in biliary tract cancer patients after surgery.

Methods

TIMs were evaluated by immunohistochemical staining of tryptase in 250 patients with resected gallbladder carcinoma (GBC) or extrahepatic bile duct carcinoma (EBDC) from Zhongshan Hospital. The relationships between TIMs and clinicopathological factors and postoperative prognosis were analyzed respectively.

Results

High TIMs infiltration was significantly correlated with prolonged overall survival (OS). Furthermore, multivariate analysis indicated TNM stage and TIMs as independent prognostic factors for OS. Patients with high TIMs infiltration appeared to significantly benefit from Gemcitabine-based ACT in the discovery and validation cohorts. Spearman analysis identified that TIMs infiltration were positively correlated with anti-tumor CD8+ T cells.

Conclusion

TIMs infiltration is an independent favorable prognostic factor in GBC and EBDC patients, which could better stratify patients with different prognosis and predict benefit from gemcitabine-based ACT.

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Effective osimertinib treatment in a patient with discordant T790 M mutation detection between liquid biopsy and tissue biopsy

Abstract

Background

We report the successful treatment of the patient with osimertinib 80 mg/day following disease progression and a discordance in the detection of a mechanism of resistance epithelial growth factor receptor (EGFR) T790 M between liquid biopsy and tissue biopsy methods.

Case presentation

A 57-year-old Hispanic male patient initially diagnosed with an EGFR 19 deletion positive lung adenocarcinoma and clinically responded to initial erlotinib treatment. The patient subsequently progressed on erlotinib 150 mg/day and repeat biopsies both tissue and liquid were sent for next-generation sequencing (NGS). A T790 M EGFR mutation was detected in the blood sample using a liquid biopsy technique, but the tissue biopsy failed to show a T790 M mutation in a newly biopsied tissue sample. He was then successfully treated with osimertinib 80 mg/day, has clinically and radiologically responded, and remains on osimertinib treatment after 10 months.

Conclusions

Second-line osimertinib treatment, when administered at 80 mg/day, is both well tolerated and efficacious in a patient with previously erlotinib treated lung adenocarcinoma and a T790 M mutation detected by liquid biopsy.

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Tumor-infiltrating mast cells predict prognosis and gemcitabine-based adjuvant chemotherapeutic benefit in biliary tract cancer patients

Abstract

Background

Methods

Results

Conclusion

TIMs infiltration is an independent favorable prognostic factor in GBC and EBDC patients, which could better stratify patients with different prognosis and predict benefit from gemcitabine-based ACT.

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Effective osimertinib treatment in a patient with discordant T790 M mutation detection between liquid biopsy and tissue biopsy

Abstract

Background

Case presentation

Conclusions

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Can too little be as bad as too much?

By Madhava Sai Sivapuram

"Any substance which is taken too much or too little is poisonous to our body whether it is a drug or a diet". These were the exact words told by my pharmacology professor when I was studying pharmacology. I thought yes, if there is excessive use of drugs, it is going to cause adverse drug reactions, whereas too little may not help us recover. With regards to the human diet, too much can cause obesity which is a risk for many diseases, whereas too little will make you undernourished. I never thought that a person's diet could be a cause of a life-threatening situation.

I faced such a situation during my BMJ Case Reports elective period[1] It was a completely new environment for me where hospital experiences a very good outpatient and inpatient flow. It was the 3rd or 4th day of my electives where I was still trying to understand the workflow of the hospital. I came across a middle-aged lady waiting outside the ward for my professor, as he was the attending physician of her father, who was admitted due to sudden fall on the ground, following a decrease in blood pressure. He had been taking medication for diabetes and hypertension for the past 10 years.

My professor had asked me to take the patient history and find out the reason for the fall in the blood pressure, but I could not do that as the patient was discharged on the same day.

It was a 3-week elective and I enjoyed working alongside my professor, who always gave me a new prospect to think about. Two days before my departure from the hospital, I got a chance to meet the patient and the family again; they had come in for a follow-up. This time the patient load in the OPD was not as high. My professor spends a lot of time with patients discussing their history and always tells me the cause of the problem is always in the patient's history. If we could figure this out, we would solve the puzzle, which is the beauty of medicine.

The lady told us that her father was having a problem with his blood pressure and during her recent visit to the family doctor, she was told that he should reduce his salt intake. She misunderstood the instruction to be that he should eat no salt at all, and she started cooking dishes exclusively for him without salt in them and was taking extra care that he was not eating any food that contained salt.

From this, we learned that her misunderstanding had cost them a lot of money and precious time. We explained to them what had gone wrong with the patient and suggested they increase his salt intake to a certain threshold.

This BMJ Case Reports elective experience has led me to remember my pharmacology professor's words practically in a real-life scenario. It also made me understand how important it is to fully inform the patient and their attendants, and also the necessity of checking their understanding. Any misunderstanding with our health education comes at a huge price for the patients and their attendants.

I acknowledge Professor Rakesh Biswas under whom I did this elective.

References:

http://promotions.bmj.com/jnl/bmj-case-reports-student-electives-2/

Competing Interests

None Declared

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Migration of a fractured inferior vena cava filter strut to the right ventricle of the heart

Inferior vena cava (IVC) filters are increasingly used in patients with recurrent venous thromboembolism in whom anticoagulation is contraindicated or intolerable. Migration of fragments is a known complication of IVC filter use. We present a case of a 32-year-old man, who presented with right-sided chest pain believed to be caused by a migrated IVC fragment to the right ventricle. The filter was removed by an endovascular cook forceps with the assistance of intracardiac echocardiography. This case serves as an addition to the existing reports of successful removal of intracardiac fragments via minimally invasive endovascular approach, amid a larger number of intracardiac fragments that have been removed by an open-heart approach.

http://ift.tt/2FVNA5Z

Sequential retinal necrosis secondary to varicella zoster in unrecognised long-standing HIV infection: patient safety report

A retired woman with left ophthalmic shingles of over 2 years' duration attended with bilateral vision loss and systemic upset. Acute retinal necrosis with detachment was detected on right fundus examination. Cataract in left eye precluded funduscopy. Ocular ultrasonography revealed fibrotic retinal detachment in the left eye. MRI brain and orbits also showed signals of retinal detachment. No abnormal MRI signal within the optic nerve or brain was found. Varicella zoster virus was detected in ocular aqueous and blood samples. High-dose intravenous acyclovir was administered. HIV test was positive with a very low CD4 count. Antiretroviral medications were prescribed. There was no recovery of vision. She was certified as blind, and social services were involved in seeking to provide alterations to her home in view of her severe disability. This case highlights the importance of suspecting HIV in patients with severe or chronic ophthalmic shingles. Images and implications for clinical practice are presented.

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Serpentine thrombus in the heart: a rare case of trapped thrombus in patent foramen ovale

A 77-year-old Caucasian woman with recent abdominal surgery was diagnosed with multiple paradoxical systemic emboli in the mesenteric and renal circulation. Diagnosis was made by direct visualisation of a serpentine thrombus traversing both atria through patent foramen ovale (PFO) by transesophageal echocardiogram (TEE). Concomitantly, the patient was found to have deep venous thrombosis and pulmonary embolism. A decision was made to pursue cardiothoracic surgery preceded by inferior vena cava filter placement. She was started on intravenous anticoagulation. Repeat TEE was negative for thrombus and the patient did not present any new clinical signs of embolisation by this time. Consequently, the treatment plan was modified and the patient received oral systemic anticoagulation followed by PFO closure with the use of St. Jude Amplatzer Cribriform septal occluder device. During the outpatient follow-up the patient was asymptomatic and there was no significant flow through the device on transthoracic echocardiogram.

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Self-harm scar revision

This report discusses in detail the case of a patient who underwent a scar revision procedure to have her characteristic self-harm scars altered. A detailed insight into the patient's perspective was gained through semistructured interviews conducted at 6 weeks and 6 months postoperatively. The interviews found that an equally if not more conspicuous scar that was distinct from those created from self-harm had a pronounced psychological benefit for the patient. This article calls for more active management of the psychological sequelae of self-harm scars, with the need to facilitate access to surgical treatment in certain cases.

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Metastatic primary anorectal melanoma developing in a patient treated for multicentric glioblastoma multiforme: two rare malignancies presenting in synchronicity

Description

A 66-year-old woman presented with complaints of dizziness, headache and forgetfulness, which had been worsening over the last 2 months. General physical examination revealed weakness in the left upper and lower limbs (power 4/5) with spasticity (deep tendon reflexes 3+ on left side). A non-contrast MRI brain revealed a mass lesion involving the right thalamus and another lesion in the right cerebellar peduncle. Both lesions were hyperintense on T2 and hypointense on T1 sequences (figure 1). A stereotactic biopsy from the thalamic lesion revealed glioblastoma multiforme (WHO Grade IV) on histopathological evaluation and immunohistochemistry (Ki67 index: 15%–20%). Due to financial constraints, O(6)-methylguanine-DNA methyltransferase(MGMT) promoter methylation status was not determined.

Figure 1

Pretreatment non-contrast MRI images of multicentric glioma. (A) T1-weighted axial image reveals a hypointense space-occupying lesion in the right thalamus involving the right basal ganglia (red arrow). (B) T1-weighted axial image reveals a hypointense space-occupying lesion in the...

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Renal injury in a patient with lumbar scoliosis

Kidney laceration following blunt trauma is responsible for up to 3% of trauma cases. The risk factors associated with renal injury are attributed to the risks of mechanical injury. However, anatomical variations that may accelerate the insult of injury are poorly documented. This case report describes a 25-year-old with degenerative lumbar scoliosis who presented with flank pain and visible haematuria following a low-impact injury. The patient had a grade IV renal injury. The curvature of the spine, shown on CT imaging, revealed a reduced retroperitoneal space around the left kidney. This case explores lumbar scoliosis as a risk factor for kidney laceration. We hypothesise that this increased risk is associated with asymmetry of the spine and reduced anatomical space in the retroperitoneum. Patients with lumbar scoliosis may be considered a high-risk category for renal injury, following low-impact trauma.

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FAST examination diagnosing bladder rupture following blunt pelvic trauma

Description

A 52-year-old man presented as a level 2 trauma notification after a plywood fell on him from 15 feet. On presentation, he was evaluated according to Advanced Trauma Life Support (ATLS) protocol. Secondary survey was significant for suprapubic tenderness and abrasions to bilateral hips. A focused assessment with sonography in trauma (FAST) examination was performed, showing echogenic fluid filling the bladder (video 1).

Video 1

Focused assessment with sonography in trauma examination performed in the trauma bay showing echogenic fluid filling the bladder.

A Foley catheter was placed, and gross haematuria was noted. X-ray in the trauma bay showed fractures of the left superior and inferior pubic rami (figure 1). Subsequently, a CT cystogram was performed which showed large clot within the bladder with small extraperitoneal extravasation (figure 2). The injury was managed with transurethral Foley and gentle...

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Severe autosomal dominant polycystic kidney disease

Description

A 61-year-old man with a known history of autosomal dominant polycystic kidney disease (ADPKD) and stage IV chronic kidney disease presented with a 6-month history of abdominal pain, nausea, vomiting and fatigue. In addition to the ADPKD, the right kidney had a 4.4 cm inferior pole mass concerning for renal cell carcinoma (RCC). Preoperative imaging (figure 1), a coronal CT of abdomen and pelvis, demonstrates bilateral ADPKD. His total kidney volume was calculated to be 9980.5 mL, which in combination with his age made him a '1E' (most severe) based on the Mayo Clinic risk stratification schema. The following aggregate of issues led the patient to undergo bilateral open nephrectomies: the suspicion for malignancy associated with the right renal mass, a slight increase in malignancy risk associated with polycystic kidney disease in general, and the likely need for postoperative dialysis if left with only a single poorly...

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Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup

Abstract

Purpose

The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [¹⁸F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup.

Methods

Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level.

Results

Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1–42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10⁻³ mm²/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = −0.31 ± 0.27, p < 0.05).

Conclusion

Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

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Radiologic and pathologic response to neoajuvant chemotherapy predicts survival in patients undergoing the liver-first approach for synchronous colorectal liver metastases

Publication date: Available online 21 March 2018
Source:European Journal of Surgical Oncology
Author(s): Giammauro Berardi, Marc De Man, Stéphanie Laurent, Peter Smeets, Federico Tomassini, Riccardo Ariotti, Anne Hoorens, Jo van Dorpe, Oswald Varin, Karen Geboes, Roberto I. Troisi
PurposeTo investigate the short- and long-term outcomes of liver first approach (LFA) in patients with synchronous colorectal liver metastases (CRLM), evaluating the predictive factors of survival.MethodsSixty-two out of 301 patients presenting with synchronous CRLM underwent LFA between 2007 and 2016. All patients underwent neoadjuvant chemotherapy. After neoadjuvant treatment patients were re-evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Liver resection was scheduled after 4-6 weeks. Changes in non-tumoral parenchyma and the tumor response according to the Tumor Regression Grade score (TRG) were assessed on surgical specimens. Primary tumor resection was scheduled 4-8 weeks following hepatectomy.ResultsFive patients out of 62 (8.1%) showed "Progressive Disease" at re-evaluation after neoadjuvant chemotherapy, 22 (35.5%) showed "Stable Disease" and 35 (56.5%) "Partial Response"; of these latter, 29 (82%) showed histopathologic downstaging. The 5-year survival (OS) rate was 55%, while the 5-year disease-free survival (DFS) rate was 16%. RECIST criteria, T-stage, N-stage and TRG were independently associated with OS. Bilobar presentation of disease, RECIST criteria, R1 margin and TRG were independently associated with DFS. Patients with response to neoadjuvant chemotherapy had better survival than those with stable or progressive disease (radiological response 5-y OS: 65% vs. 50%; 5-y DFS: 20% vs. 10%; pathological response 5-y OS: 75% vs. 56%; 5-y DFS: 45% vs. 11%).ConclusionsLFA is an oncologically safe strategy. Selection is a critical point, and the best results in terms of OS and DFS are observed in patients having radiological and pathological response to neoadjuvant chemotherapy.

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Multiple Inhibitory Mechanisms of Lidocaine on Bradykinin Receptor Activity in Model Sensory Neurons

Background and Objectives Local anesthetics (LAs) are often infiltrated subcutaneously for localized perioperative numbing. In addition to blocking nerve conduction, LAs act on pathways used by a variety of pain-inducing and inflammatory mediators. We describe the effects in isolated model sensory neurons of LAs on responses to the algogenic and sensitizing peptide, bradykinin (BK). Methods ND/7 sensory neurons were stimulated by different concentrations of BK in the presence or absence of LAs, with transient increases in intracellular calcium (Δ[Ca+2]in) detected fluorometrically in fields of cells. Equilibrium saturable binding of radiolabeled BK also was conducted on the same type of cells, with and without LA. Results Responses to low BK (5 nM) were inhibited by lidocaine at 1 mM (approximately 35% inhibition) and 10 mM (approximately 70% inhibition), whereas responses to high BK (100 nM) were unaffected by 1 mM yet inhibited (approximately 75%) by 10 mM lidocaine. Bupivacaine (1 and 2 mM) did not reduce peak Δ[Ca+2]in (using 5 nM BK). Lidocaine's quaternary derivative, QX-314 (10 mM), also was ineffective on peak Ca+2 (5 nM BK). Saturation binding of BK showed that lidocaine lowered the binding capacity (Bmax) without changing the KD, consistent with noncompetitive inhibition. Conclusions At subclinical concentrations, lidocaine suppresses BK's activation of model sensory neurons. This effect adds to the known analgesic mechanisms of LAs and likely contributes to the reduction of postincisional pain. Accepted for publication November 1, 2017. Address correspondence to: Gary R. Strichartz, PhD, Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, MRB611, 75 Francis St, Boston, MA 02115 (e-mail: gstrichartz@partners.org). Funding for this work was provided in part by the US Public Health Service, National Institutes of Health, from grants NIGMS R01-GM35647 and NIH/NCI R01-CA080153. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Anatomical Study of the Innervation of Anterior Knee Joint Capsule: Implication for Image-Guided Intervention

Background and Objectives The knee joint is the most common site of osteoarthritis. While joint replacement is considered an ultimate solution, radiofrequency denervation may be contemplated in some cases. Radiofrequency ablation requires precise localization of the articular branches innervating the joint capsule. The objective of this cadaveric study was to determine the source, course, relationships, and frequency of articular branches innervating the anterior knee joint capsule. Methods Fifteen knees were meticulously dissected. The number and origin of the articular branches were recorded, and their distribution defined by quadrants. Their relationships to anatomical landmarks were identified. Results The articular branches terminated in 1 of the 4 quadrants with minimal overlap. In all specimens, the superolateral quadrant was innervated by the nerve to vastus lateralis, nerve to vastus intermedius, superior lateral genicular and common fibular nerves; inferolateral by the inferior lateral genicular and recurrent fibular nerves; superomedial by the nerve to vastus medialis, nerve to vastus intermedius and superior medial genicular nerve; and inferomedial by the inferior medial genicular nerve. In 3 specimens, the inferomedial quadrant also received innervation from the infrapatellar branch of saphenous nerve. All articular branches except the nerves to vastus lateralis and medialis course at the periosteal level. Conclusions The frequency map of the articular branches provides an anatomical basis for the development of new clinical protocols for knee radiofrequency denervation and perioperative pain management. Accepted for publication January 15, 2018. Address correspondence to: Philip W.H. Peng, MBBS, Department of Anesthesia, University of Toronto, 399 Bathurst St, McL 2-405 Toronto, Ontario, Canada M5T 2S8 (e-mail: philip.peng@uhn.ca). The authors declare no conflict of interest. Funding was provided through Merit Award in Research, Department of Anesthesia, University of Toronto (to P.W.H.P.) and Physicians' Service Incorporated Foundation award (to P.W.H.P. and K.L.). Interim data from this work were presented at the 2017 Annual Meeting of American Association of Clinical Anatomists in Minneapolis, MN, on July 17 to 21, 2017; at the 2017 World Academy of Pain Medicine Ultrasonography Annual Meeting and Workshop in Miami, FL, on January 13 to 15, 2017; and at the 2017 Study in Multidisciplinary Pain Research—International Symposium of Ultrasound in Regional Anesthesia Congress in Florence, Italy, on March 29 to April 1, 2017. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Interfascial Plane Blocks: Back to Basics

Ultrasound-guided interfascial plane blocks are a recent development in modern regional anesthesia research and practice and represent a new route of transmission for local anesthetic to various anatomic locations, but much more research is warranted. Before becoming overtaken with enthusiasm for these new techniques, a deeper understanding of fascial tissue anatomy and structure, as well as precise targets for needle placement, is required. Many factors may influence the ultimate spread and quality of resulting interfascial plane blocks, and these must be understood in order to best integrate these techniques into contemporary perioperative pain management protocols. Accepted for publication October 29, 2017. Address correspondence to: Hesham Elsharkawy, MD, MBA, MSc, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Ave, E-31 Cleveland, OH 44195 (e-mail: elsharh@ccf.org). No external funding and no competing interests were declared. H.E. has received unrestricted educational funding from PAJUNK (Norcross, GA) and is consultant for PACIRA (Troy Hills, NJ). A.P. has received honoraria from GE Healthcare, Pittsburgh, PA, for teaching. E.R.M. has received unrestricted educational program funding from Halyard Health (Alpharetta, GA). These companies had no input into any aspect of the present project design or manuscript preparation. Permission to use images was obtained from the Cleveland Clinic Department of Art Photography. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Histopathologic analysis of stage pT1b kidney neoplasms for optimal surgical margins of nephron-sparing surgery

Abstract

Objective

To evaluate the pathological features and define the optimal surgical margins (SM) of nephron-sparing surgery (NSS) for kidney neoplasms 4–7 cm (stage pT1b) on preoperative imaging.

Materials and methods

The retrospective study included 748 patients who were diagnosed stage pT1b renal tumors and underwent either radical nephrectomy (RN, n = 475) or NSS (n = 273) from January 2004 to March 2017. The tumor size, pathological subtype, Fuhrman grade, status of peritumoral pseudocapsule (PC) and tumor multifocality were recorded. The relationship between peritumoral PC and positive SM was calculated statistically by Fisher's exact probability test.

Results

The mean tumor diameter was 5.4 cm (range: 4.1–7.0 cm), 65 (8.7%) cases were discovered with multifocal lesions and 686 (91.7%) were surrounded with peritumoral PC in all 748 specimens. 57 (8.3%) of 686 cases were proved with tumor infiltrated beyond PC [infiltration (+)], and the presence of PC infiltration (+) was significantly correlated with positive SM (p = 0.016). The infiltrative depth of tumor cells into renal parenchyma beyond PC was all limited in 3 mm and the proportion of ≤ 1, 1–2 and 2–3 mm was 21.1% (12/57), 59.6% (34/57) and 19.3% (11/57), respectively.

Conclusions

Our report indicates a 3 mm excisional margin is acceptable to ensure negative SM when operating NSS on stage pT1b kidney neoplasms.

from Cancer via ola Kala on Inoreader http://ift.tt/2HS38IN
via IFTTT

Histopathologic analysis of stage pT1b kidney neoplasms for optimal surgical margins of nephron-sparing surgery

Abstract

Objective

To evaluate the pathological features and define the optimal surgical margins (SM) of nephron-sparing surgery (NSS) for kidney neoplasms 4–7 cm (stage pT1b) on preoperative imaging.

Materials and methods

Results

Conclusions

Our report indicates a 3 mm excisional margin is acceptable to ensure negative SM when operating NSS on stage pT1b kidney neoplasms.

from Cancer via ola Kala on Inoreader http://ift.tt/2HS38IN
via IFTTT

Histopathologic analysis of stage pT1b kidney neoplasms for optimal surgical margins of nephron-sparing surgery

Abstract

Objective

To evaluate the pathological features and define the optimal surgical margins (SM) of nephron-sparing surgery (NSS) for kidney neoplasms 4–7 cm (stage pT1b) on preoperative imaging.

Materials and methods

Results

Conclusions

Our report indicates a 3 mm excisional margin is acceptable to ensure negative SM when operating NSS on stage pT1b kidney neoplasms.

http://ift.tt/2HS38IN

From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Abstract

Background

Typically, women in South Africa (SA) are diagnosed with breast cancer when they self-present with symptoms to health facilities. The aim of this study was to determine the pathway that women follow to breast cancer care and factors associated with this journey.

Methods

A cross-sectional study was conducted at a tertiary hospital in the Western Cape Province, SA, between May 2015 and May 2016. Newly diagnosed breast cancer patients were interviewed to determine their socio-demographic profile; knowledge of risk factors, signs and symptoms; appraisal of breast changes; clinical profile and; key time events in the journey to care. The Model of Pathways to Treatment Framework underpinned the analysis. The total time (TT) between a woman noticing the first breast change and the date of scheduled treatment was divided into 3 intervals: the patient interval (PI); the diagnostic interval (DI) and the pre-treatment interval (PTI). For the PI, DI and PTI a bivariate comparison of median time intervals by various characteristics was conducted using Wilcoxon rank-sum and Kruskal-Wallis tests. Cox Proportional-Hazards models were used to identify factors independently associated with the PI, DI and PTI.

Results

The median age of the 201 participants was 54 years, and 22% presented with late stage disease. The median TT was 110 days, with median patient, diagnostic and pre-treatment intervals of 23, 28 and 37 days respectively. Factors associated with the PI were: older age (Hazard ratio (HR) 0.59, 95% CI 0.40–0.86), initial symptom denial (HR 0.43, 95% CI 0.19–0.97) and waiting for a lump to increase in size before seeking care (HR 0.51, 95% CI 0.33–0.77). Women with co-morbidities had a significantly longer DI (HR 0.67, 95% CI 0.47–0.96) as did women who mentioned denial of initial breast symptoms (HR 4.61, 95% CI 1.80–11.78). The PTI was associated with late stage disease at presentation (HR 1.78, 95% CI 1.15–2.76).

Conclusion

The Model of Pathways to Treatment provides a useful framework to explore patient's journeys to care and identified opportunities for targeted interventions.

from Cancer via ola Kala on Inoreader http://ift.tt/2GbXXpS
via IFTTT

Histopathologic analysis of stage pT1b kidney neoplasms for optimal surgical margins of nephron-sparing surgery

Abstract

Objective

To evaluate the pathological features and define the optimal surgical margins (SM) of nephron-sparing surgery (NSS) for kidney neoplasms 4–7 cm (stage pT1b) on preoperative imaging.

Materials and methods

Results

Conclusions

Our report indicates a 3 mm excisional margin is acceptable to ensure negative SM when operating NSS on stage pT1b kidney neoplasms.

http://ift.tt/2HS38IN

From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Abstract

Background

Methods

Results

Conclusion

The Model of Pathways to Treatment provides a useful framework to explore patient's journeys to care and identified opportunities for targeted interventions.

http://ift.tt/2GbXXpS