Tinetti mobility test is related to muscle mass and strength in non-institutionalized elderly people

Abstract

Elderly people are characterized by a high prevalence of falls and sarcopenia. However, the relationship among Tinetti mobility test (TMT) score, a powerful tool to detect elderly people at risk of falls, and sarcopenia is still not thoroughly investigated. Thus, to determine the relationship between TMT score and muscle mass and strength, 337 elderly participants (mean age 77.1 ± 6.9 years) admitted to comprehensive geriatric assessment were enrolled. TMT score, muscle mass by bioimpedentiometer, and muscle strength by grip strength were evaluated. Muscle mass progressively decreased as TMT score decreased (from 15.3 ± 3.7 to 8.8 ± 1.8 kg/m²; p for trend <0.001). Similarly, muscle strength decreased progressively as Tinetti score decreased (from 34.7 ± 8.0 to 23.7 ± 8.7 kg; p for trend 0.001). Linear regression analysis demonstrated that TMT score is linearly related with muscle mass (y = 4.5x + 0.4, r = 0.61; p < 0.01) and strength (y = 14.0x + 0.8, r = 0.53; p < 0.01). Multivariate analysis confirms the strong relationship between the TMT score and muscle mass (r = 0.48, p = 0.024) and strength (r = 0.39, p = 0.046). The present study indicates that TMT score is significantly related to muscle mass and strength in non-institutionalized elderly participants. This evidence suggests that TMT score, together with evaluation of muscle mass and strength, may identify sarcopenic elderly participants at high risk of falls.

from Cancer via ola Kala on Inoreader http://ift.tt/2bpFiU4
via IFTTT

An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma

Summary

Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domain-containing molecule-3. In the present study, we investigated expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin embedded tissue samples, and subsequently studied the detailed mechanism of up-regulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines. We found that macrophages in lymphoma tissues of almost all cases of adult T-cell leukemia/lymphoma (ATLL), follicular lymphoma, and diffuse large B-cell lymphoma expressed PD-L1. Cell culture studies showed that the conditioned medium of ATL-T and SLVL cell lines induced increased expression of PD-L1/2 on macrophages, and that this PD-L1/2 overexpression was dependent on activation of signal transducer and activator of transcription 3 (Stat3). In vitro studies including cytokine array analysis showed that IL-27 (heterodimer of p28 and EBI3) induced overexpression of PD-L1/2 on macrophages via Stat3 activation. Since lymphoma cell lines produced IL-27B(EBI3) but not IL-27p28, it was proposed that the IL-27p28 derived from macrophages and the IL-27B(EBI3) derived from lymphoma cells formed an IL-27(heterodimer) that induced PD-L1/2 overexpression. Although the significance of PD-L1/2 expressions on macrophages in lymphoma progression has never been clarified, an IL-27-Stat3 axis might be a target for immunotherapy for lymphoma patients.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2bUF6i2
via IFTTT

Coming to terms with NIFTP: A provisional approach for cytologists

The new term NIFTP (noninvasive follicular thyroid neoplasm with papillary-like nuclear features) for some thyroid tumors poses significant challenges for cytopathologists. This commentary represents a provisional approach to NIFTP that others may consider adopting and that will hopefully prompt further discussion and research on how NIFTP should fit into future cytology practice.

from Cancer via ola Kala on Inoreader http://ift.tt/2ceZn5A
via IFTTT

Quantification of PD-L1 and PD-1 expression on tumor and immune cells in non-small cell lung cancer (NSCLC) using non-enzymatic tissue dissociation and flow cytometry

Abstract

Objective

We report a truly quantitative technology for PD-L1 expression in non-small cell lung cancer (NSCLC). In addition, we present a non-enzymatic technology that creates a cell suspension from fresh tumor tissue so that either fine-needle aspiration (FNA) or fresh tissue can be used in this assay.

Methods

Non-enzymatic tissue homogenization (IncellPREP; IncellDx, Menlo Park, California) was performed on 4-mm punch biopsies. An FNA was taken from the same tumor to create matched sample sets. Cells were labeled with antibodies directed against CD45, PD-1, and PD-L1 and then stained with DAPI to identify intact, single cells, and to analyze cell cycle.

Results

Comparing the IncellPREP homogenization and FNA demonstrated a strong correlation (r ² − 0.8) for expression of PD-L1. We compared PD-L1 expression by flow cytometry using a 1 % cutoff for positivity in the tumor cell population and a 1 % cutoff of cells with at least 1+ intensity in immunohistochemically stained tissue sections as positive. Ten of 12 lung tumor samples were concordant while 2 were discordant. PD-L1 expression by flow cytometry varied widely (1.2–89.4 %) even in the positive concordant cases. In addition, PD-L1 expression in the aneuploid tumor population did not necessarily agree with the expression in the diploid tumor population.

Summary

Fine, unequivocal quantification of PD-L1 on tumor and immune cells in NSCLC may allow for better prediction of response to therapies. The present study also offers a technology that can create a universal sample type from either FNA or fresh tissue.

from Cancer via ola Kala on Inoreader http://ift.tt/2blCh7p
via IFTTT

Quantification of PD-L1 and PD-1 expression on tumor and immune cells in non-small cell lung cancer (NSCLC) using non-enzymatic tissue dissociation and flow cytometry

Abstract

Objective

We report a truly quantitative technology for PD-L1 expression in non-small cell lung cancer (NSCLC). In addition, we present a non-enzymatic technology that creates a cell suspension from fresh tumor tissue so that either fine-needle aspiration (FNA) or fresh tissue can be used in this assay.

Methods

Non-enzymatic tissue homogenization (IncellPREP; IncellDx, Menlo Park, California) was performed on 4-mm punch biopsies. An FNA was taken from the same tumor to create matched sample sets. Cells were labeled with antibodies directed against CD45, PD-1, and PD-L1 and then stained with DAPI to identify intact, single cells, and to analyze cell cycle.

Results

Comparing the IncellPREP homogenization and FNA demonstrated a strong correlation (r ² − 0.8) for expression of PD-L1. We compared PD-L1 expression by flow cytometry using a 1 % cutoff for positivity in the tumor cell population and a 1 % cutoff of cells with at least 1+ intensity in immunohistochemically stained tissue sections as positive. Ten of 12 lung tumor samples were concordant while 2 were discordant. PD-L1 expression by flow cytometry varied widely (1.2–89.4 %) even in the positive concordant cases. In addition, PD-L1 expression in the aneuploid tumor population did not necessarily agree with the expression in the diploid tumor population.

Summary

Fine, unequivocal quantification of PD-L1 on tumor and immune cells in NSCLC may allow for better prediction of response to therapies. The present study also offers a technology that can create a universal sample type from either FNA or fresh tissue.

from Cancer via ola Kala on Inoreader http://ift.tt/2blCh7p
via IFTTT

Epidemiology of cutaneous melanoma in Sweden - stage specific survival and rate of recurrence

ABSTRACT

Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted five-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with five-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stage I and IV patients, respectively. In addition to stage, male gender, age, and circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments. This article is protected by copyright. All rights reserved.

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

Quantification of PD-L1 and PD-1 expression on tumor and immune cells in non-small cell lung cancer (NSCLC) using non-enzymatic tissue dissociation and flow cytometry

Abstract

Objective

We report a truly quantitative technology for PD-L1 expression in non-small cell lung cancer (NSCLC). In addition, we present a non-enzymatic technology that creates a cell suspension from fresh tumor tissue so that either fine-needle aspiration (FNA) or fresh tissue can be used in this assay.

Methods

Non-enzymatic tissue homogenization (IncellPREP; IncellDx, Menlo Park, California) was performed on 4-mm punch biopsies. An FNA was taken from the same tumor to create matched sample sets. Cells were labeled with antibodies directed against CD45, PD-1, and PD-L1 and then stained with DAPI to identify intact, single cells, and to analyze cell cycle.

Results

Comparing the IncellPREP homogenization and FNA demonstrated a strong correlation (r ² − 0.8) for expression of PD-L1. We compared PD-L1 expression by flow cytometry using a 1 % cutoff for positivity in the tumor cell population and a 1 % cutoff of cells with at least 1+ intensity in immunohistochemically stained tissue sections as positive. Ten of 12 lung tumor samples were concordant while 2 were discordant. PD-L1 expression by flow cytometry varied widely (1.2–89.4 %) even in the positive concordant cases. In addition, PD-L1 expression in the aneuploid tumor population did not necessarily agree with the expression in the diploid tumor population.

Summary

Fine, unequivocal quantification of PD-L1 on tumor and immune cells in NSCLC may allow for better prediction of response to therapies. The present study also offers a technology that can create a universal sample type from either FNA or fresh tissue.

from Cancer via ola Kala on Inoreader http://ift.tt/2blCh7p
via IFTTT

Dynamic Imaging Grade of Swallowing Toxicity (DIGEST): Scale development and validation

BACKGROUND

The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) is the universal framework for toxicity reporting in oncology trials. The objective of this study was to develop a CTCAE-compatible modified barium swallow (MBS) grade for the purpose of grading pharyngeal dysphagia as a toxicity endpoint in cooperative-group organ-preservation trials for head and neck cancer (HNC). It was hypothesized that a 5-point, CTCAE-compatible MBS grade (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]) based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings would be feasible and psychometrically sound.

METHODS

A modified Delphi exercise was conducted for content validation, expert consensus, and operationalization of DIGEST criteria. Two blinded raters scored 100 MBSs conducted before or after surgical or nonsurgical organ preservation. Intrarater and interrater reliability was tested with weighted κ values. Criterion validity against oropharyngeal swallow efficiency (OPSE), the Modified Barium Swallow Impairment Profile (MBSImP™©), the MD Anderson Dysphagia Inventory (MDADI), and the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) was assessed with a 1-way analysis of variance and post hoc pairwise comparisons between DIGEST grades.

RESULTS

Intrarater reliability was excellent (weighted κ = 0.82-0.84) with substantial to almost perfect agreement between raters (weighted κ = 0.67-0.81). DIGEST significantly discriminated levels of pharyngeal pathophysiology (MBSImP™©: r = 0.77; P < .0001), swallow efficiency (OPSE: r = –0.56; P < .0001), perceived dysphagia (MDADI: r = –0.41; P < .0001), and oral intake (PSS-HN diet: r = –0.49; P < .0001).

CONCLUSIONS

With the development of DIGEST, the MBS rating has been adapted to the CTCAE nomenclature of ordinal toxicity grading used in oncology trials. DIGEST offers a psychometrically sound measure for HNC clinical trials and investigations of toxicity profiles, dose responses, and predictive modeling. Cancer 2016. © 2016 American Cancer Society.

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

Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging—A prospective trial

BACKGROUND

Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single-photon emission computed tomography/computed tomography (SPECT-CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET-CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT-CT with PET-CT for the identification of nodal metastases in pediatric and AYA patients.

METHODS

Twenty-eight pediatric and AYA sarcoma patients underwent SLNB with SPECT-CT. The histological findings of the excised lymph nodes were then correlated with preoperative PET-CT imaging.

RESULTS

A median of 2.4 sentinel nodes were sampled per patient. No wound infections or chronic lymphedema occurred. SLNB identified tumors in 7 of the 28 patients (25%), including 3 patients who had normal PET-CT imaging of the nodal basin. In contrast, PET-CT demonstrated hypermetabolic regional nodes in 14 patients, and this resulted in a positive predictive value of only 29%. The sensitivity and specificity of PET-CT for detecting histologically confirmed nodal metastases were only 57% and 52%, respectively.

CONCLUSIONS

SLNB can safely guide the rational selection of nodes for biopsy in pediatric and AYA sarcoma patients and can identify therapy-changing nodal disease not appreciated with PET-CT. Cancer 2016. © 2016 American Cancer Society.

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

Tissue engineering and regenerative medicine in musculoskeletal oncology

Abstract

Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.

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

Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance

Abstract

Cancer stem cells (CSCs) are a small subpopulation of tumor cells with capabilities of self-renewal, dedifferentiation, tumorigenicity, and inherent chemo-and-radio therapy resistance. Tumor resistance is believed to be caused by CSCs that are intrinsically challenging to common treatments. A number of CSC markers including CD44, CD133, receptor tyrosine kinase, aldehyde dehydrogenases, epithelial cell adhesion molecule/epithelial specific antigen, and ATP-binding cassette subfamily G member 2 have been proved as the useful targets for defining CSC population in solid tumors. Furthermore, targeting CSC markers through new therapeutic strategies will ultimately improve treatments and overcome cancer drug resistance. Therefore, the identification of novel strategies to increase sensitivity of CSC markers has major clinical implications. This review will focus on the innovative treatment methods such as nano-, immuno-, gene-, and chemotherapy approaches for targeting CSC-specific markers and/or their associated signaling pathways.

from Cancer via ola Kala on Inoreader http://ift.tt/2bltm5W
via IFTTT

Expression of the circulating and the tissue microRNAs after surgery, chemotherapy, and radiotherapy in mice mammary tumor

Abstract

The expression of microRNAs (miRNAs), as novel biomarkers, is subject to change in many cancers. Therefore, the overall profile of miRNAs can be used for detection of cancer type, response to therapies, pathological variables, and other factors related to the disease. In this study, to evaluate miRNA expression associated with the tumor progression and response to treatment, 60 BALB/c mice received subcutaneous injections of 4T1 cells. The study includes ten groups: one group as control, six groups were euthanized at different time points to assess the role of miRNA expression in the tumor progression, and three groups received chemotherapy, radiotherapy, and surgery to evaluate miRNA expression in response to treatment. MicroRNAs were extracted from the breast tumor and the plasma samples, and their relative expressions were quantified using qRT-PCR. MiR-155 expression was increased in the plasma in the early weeks after the cell injection but decreased in the plasma after surgery and radiotherapy and also in tumor samples after chemotherapy and radiotherapy. MiR-10b expression was increased in the late weeks both in the plasma and the tumor and was decreased in the plasma after radiotherapy and surgery and in the tumor after radiotherapy. MiR-21 expression was increased in the plasma and the tumor tissue during the disease progression at the third and the fourth weeks following tumor induction but was decreased in the plasma in all the therapy groups. Interestingly, miR-125a showed a significant decrease during the tumor progression, and its expression was increased after the treatment. Our results showed that the candidate miRNAs could be divided into two groups of oncomiRs and tumor suppressor miR based on their deregulation after tumor growth and treatments. It seems that the oncomiRs in the plasma can be an ideal noninvasive candidate biomarker for the early detection of breast cancer and also for following the response of the common therapies.

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

The Glasgow Prognostic Score (GPS) is a novel prognostic indicator in advanced epithelial ovarian cancer: a multicenter retrospective study

Abstract

Purpose

The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score systems composed of C-reactive protein and albumin, has been reported to be predictive of survival in several types of malignancies. The prognostic significance of GPS in epithelial ovarian cancer (EOC) remains unclear. We conducted this study to assess the prognostic value of GPS in a cohort of patients with advanced EOC receiving neoadjuvant chemotherapy (NAC) followed by debulking surgery.

Methods

Six hundred and seventy-two patients newly diagnosed with advanced EOC were retrospectively analyzed.

Results

High GPS was significantly related to Eastern Cooperative Group performance status, histological type, histological grade and the size of residual tumor after the debulking surgery. In addition, patients with higher GPS at diagnosis achieved lower complete remission rates after NAC (P < 0.05) and had shorter progression-free survival (PFS; P < 0.001) and overall survival (OS; P < 0.001). Multivariate analysis showed high GPS was independent adverse predictors of PFS and OS.

Conclusions

Our data demonstrated that GPS at diagnosis is a powerful independent prognostic factor for advanced epithelial ovarian cancer. However, further studies are needed to prospectively validate this prognostic model and investigate the mechanisms underlying the correlation between high GPS and poor prognosis in advanced epithelial ovarian cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2bV2xH1
via IFTTT

Lay health educators increase colorectal cancer screening among Hmong Americans: A cluster randomized controlled trial

BACKGROUND

Asian Americans have lower colorectal cancer (CRC) screening rates than non-Hispanic white individuals. Hmong Americans have limited socioeconomic resources and literacy. The current randomized controlled trial was conducted to determine whether bilingual/bicultural lay health educator (LHE) education could increase CRC screening among Hmong Americans.

METHODS

A cluster randomized controlled trial was conducted among Hmong Americans in Sacramento, California. LHEs and recruited participants were randomized to intervention or control groups. The intervention group received CRC education over 3 months delivered by an LHE. The control group received education regarding nutrition and physical activity delivered by a health educator. The outcomes were changes in self-reported ever-screening and up-to-date CRC screening after 6 months.

RESULTS

All 329 participants were foreign-born with mostly no formal education, limited English proficiency, and no employment. The majority of the participants were insured and had a regular source of health care. The intervention group experienced greater changes after the intervention than the control group for ever-screening (P = .068) and being up-to-date with screening (P<.0001). In multivariable regression analyses, the intervention group demonstrated a greater increase than the control group in reporting ever-screening (adjusted odds ratio, 1.73; 95% confidence interval, 1.07-2.79) and being up-to-date with screening (adjusted odds ratio, 1.71; 95% confidence interval, 1.26-2.32). Individuals who had health insurance were found to have >4 times the odds of receiving screening, both ever-screening and up-to-date screening. A higher CRC knowledge score mediated the intervention effect for both screening outcomes.

CONCLUSIONS

A culturally and linguistically appropriate educational intervention delivered by trained LHEs was found to increase CRC screening in an immigrant population with low levels of education, employment, English proficiency, and literacy. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2bFkDw8
via IFTTT

Cancers, Vol. 8, Pages 79: Wnt5a Signaling in Cancer

Wnt5a is involved in activating several non-canonical WNT signaling pathways, through binding to different members of the Frizzled- and Ror-family receptors. Wnt5a signaling is critical for regulating normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a in regulating cancer cell invasion, metastasis, metabolism and inflammation. In this article, we review findings regarding the molecular mechanisms and roles of Wnt5a signaling in various cancer types, and highlight Wnt5a in ovarian cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2bnC5ZZ
via IFTTT

Influential Forces in Breast Cancer Surgical Decision Making and the Impact on Body Image and Sexual Function

Abstract

Background

Shared decision making with one's partner and body image satisfaction may affect surgical choices of breast cancer patients. This study analyzed whether partner opinion was associated with choice of operation and whether comfort level with one's partner was altered postoperatively.

Methods

A prospective anonymous survey was administered to breast cancer patients who underwent breast surgery between 2000 and 2014. Categorical variables were compared by χ ² or Fisher's exact test.

Results

Women who elected to undergo mastectomy with reconstruction (MR) placed greater emphasis on their own decision making than on input from their partner, surgeon, or others (56.5 vs. 8.3 vs. 23.2 vs. 12, respectively), whereas those who chose lumpectomy (L) placed similar weight on surgeon input and self-input (44.2 vs. 42.7 %). Only 7.5 % of all patients identified their partner as the greatest influence on their surgical choice. Preoperatively, the L group was the most comfortable with their partner seeing their chest (91.9 % L vs. 83.9 % MR vs. 75.9 % mastectomy alone (M); p = 0.01), and postoperatively, the comfort levels for all were remarkably decreased. Furthermore, if a patient was a candidate for L but chose MR, the role her chest played in intimacy dropped more compared with those who chose L (83.8 % L vs. 91.7 % MR; p = 0.3 preoperatively to 65.1 % L vs. 42.9 % MR; p = 0.01 postoperatively).

Conclusions

When making surgical decisions, most patients indicate that they value their own opinion over that of others. Mastectomy, regardless of reconstruction, leads to a significant reduction in comfort with one's partner postoperatively compared with lumpectomy. This information may be helpful in counseling couples at the time of consultation for breast cancer treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/2bSnP8l
via IFTTT

Intraoperative Margin Assessment in Wire-Localized Breast-Conserving Surgery for Invasive Cancer: A Population-Level Comparison of Techniques

Abstract

Background

Various intraoperative margin assessment techniques have been shown to improve margin status in breast-conserving surgery (BCS) for cancer. Our study sought to evaluate multiple margin assessment techniques on a population level and determine their effects on margin status.

Methods

Patients undergoing wire-localized BCS for invasive cancer in Alberta, Canada, were assessed using a prospectively entered database of patient and tumor characteristics. Margin status was obtained from chart review. Four margin assessment techniques were studied: specimen mammography (SM), intraoperative ultrasound (US), gross assessment by pathologist (GP), and frozen section analysis (FS). Multivariable logistic regression adjusting for confounders was used to assess effect of any technique on margin status, with secondary analysis evaluating effects of individual techniques.

Results

Margin assessment was performed in 1165 of 1649 patients (71 %). The overall positive margin rate was 20.8 %. Adjusting for confounders, we found no difference in the odds of a positive margin with any margin assessment technique versus wire localization alone (OR 0.79, p = 0.22, 95 % CI 0.54–1.16). Individually, both GP and FS reduced the risk of a positive margin (GP–OR 0.56, p = 0.002, 95 % CI 0.39–0.81; FS–OR 0.43, p = 0.046, 95 % CI 0.19–0.98), whereas SM and US showed no effect (SM–OR 1.23, p = 0.29, 95 % CI 0.84–1.81; US–OR 1.09, p = 0.83, 95 % CI 0.50–2.37).

Conclusions

Use of any margin assessment technique did not improve margin status compared to wire localization alone. Gross assessment by pathologist and frozen section analysis improved margin status compared to imaging-alone techniques. Further exploration is required to refine optimal margin assessment methods.

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

What Are We Missing?

from Cancer via ola Kala on Inoreader http://ift.tt/2bSp086
via IFTTT

Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy

Abstract

The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

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

Genomic Impact of Neoadjuvant Therapy on Breast Cancer: Incomplete Response is Associated with Altered Diagnostic Gene Signatures

Abstract

Purpose

Neoadjuvant therapy (NAT) has been shown to clinically downstage locally advanced breast cancers. This study aimed to determine whether a meaningful change in gene signatures occurs between pre- and post-NAT breast cancers for patients who do not achieve a pathologic complete response.

Methods

The current analysis included women from the prospective Neoadjuvant Breast Registry Symphony Trial who had breast cancer and awaited NAT. MammaPrint and BluePrint (Agendia, Inc., Irvine, CA) assays were performed on pre- and post-NAT breast tumor samples.

Results

At the completion of NAT, 93 patients with residual disease had their remaining tumor analyzed for MammaPrint and BluePrint. Of 93 patients, 21 switched tumor classification: 16 from high risk (HR) to low risk (LR) and 1 from LR to HR (p < 0.001). Four additional patients switched molecular subtype but remained HR. Although only 17 patients switched in their MammaPrint risk classification, the underlying MPIndex was significantly altered after treatment across all patients (p < 0.001). Additionally, the three BluePrint indices for luminal, human epidermal growth factor receptor 2 (HER2), and basal type also were significantly altered after treatment, in a subtype-dependent manner.

Conclusion

This substudy showed that NAT significantly altered the genomic signature of the patient's breast cancer compared with the patient's pretreatment genomic profile. These alterations occurred in a subtype-dependent manner, suggesting that NAT may have either eliminated the most susceptible tumor subclone, leaving the treatment resistant clone with a different genetic signature, or altered molecular characteristics of the original cancer.

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

Tweeting the Meeting: Twitter Use at The American Society of Breast Surgeons Annual Meeting 2013–2016

Abstract

Background

Twitter social media is being used to disseminate medical meeting information. Meeting attendees and other interested parties have the ability to follow and participate in conversations related to meeting content. We analyzed Twitter activity generated from the 2013–2016 American Society of Breast Surgeons Annual Meetings.

Methods

The Symplur Signals database was used to determine number of tweets, tweets per user, and impressions for each meeting. The number of unique physicians, patients/caregivers/advocates, and industry participants was determined. Physician tweeters were cross-referenced with membership and attendance rosters. Tweet transcripts were analyzed for content and tweets were categorized as either scientific, social, administrative, industry promotion, or irrelevant.

Results

From 2013 to 2016, the number of tweets increased by 600 %, the number of Twitter users increased by 450 %, and the number of physician tweeters increased by 457 %. The number of impressions (tweets × followers) increased from more than 3.5 million to almost 20.5 million, an increase of 469 %. The majority of tweets were informative (70–80 %); social tweets ranged from 13 to 23 %. A small percentage (3–6 %) of tweets were related to administrative matters. There were very few industry or irrelevant tweets.

Conclusions

Twitter social media use at the American Society of Breast Surgeons annual meeting showed a substantial increase during the time period evaluated. The use of Twitter during professional meetings is a tremendous opportunity to share information. The authors feel that medical conference organizers should encourage Twitter participation and should be educating attendees on the proper use of Twitter.

from Cancer via ola Kala on Inoreader http://ift.tt/2bLr1Fu
via IFTTT

The Impact of the Affordable Care Act on North Carolinian Breast Cancer Patients Seeking Financial Support for Treatment

Abstract

Background

The Affordable Care Act (ACA) was instated on 23 March 2010 to improve healthcare quality, reduce costs, and increase access. The Pretty in Pink Foundation (PIPF), a non-profit 501(C)(3) organization in North Carolina, provides financial assistance and in-kind support to individuals seeking help with breast cancer care. The objective of this study was to determine whether sociodemographic variables and treatment services varied among PIPF recipients since enactment of the ACA.

Methods

North Carolinians who received financial assistance from the PIPF between 1 January 2013 and 31 December 2014 were included in the study, and the cohort was divided into two groups based on receipt of assistance before or after the enactment of the ACA. Descriptive statistics were tabulated as frequencies. Comparative univariate analysis between both groups was conducted using the χ ² and Mann–Whitney U tests. All tests were two-sided and a p value <0.05 was considered statistically significant. All analyses were conducted using Stata.

Results

Overall, 1016 individuals fulfilled the inclusion criteria, and the median age of the cohort was 49 years (interquartile range 45–55). The ACA groups did not differ significantly by age, race, and sex; however, the groups varied with respect to income, employment, and clinical stage. In addition, the groups differed on the types of services for which they received financial assistance, but no difference was observed between groups with respect to insurance status.

Conclusion

Since the enactment of the health insurance market component of the ACA, there has been a reduction in subjects receiving assistance from the PIPF; however, no change in their insurance status has been observed.

from Cancer via ola Kala on Inoreader http://ift.tt/2bSo0ko
via IFTTT

Early Adoption of the SSO-ASTRO Consensus Guidelines on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: Initial Experience from Memorial Sloan Kettering Cancer Center

Abstract

Background

Reexcision rates in patients undergoing breast-conserving surgery (BCS) for early-stage invasive breast cancer are highly variable. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines to help standardize practice. We sought to determine reexcision rates before and after guideline adoption at our institution.

Methods

We identified patients with stage I or II invasive breast cancer initially treated with BCS between June 1, 2013, and October 31, 2014. Margins were defined as positive (tumor on ink), close (≤1 mm), or negative (>1 mm), and were recorded for both invasive cancer and ductal carcinoma-in situ (DCIS) components. Reexcision rates were quantified, characteristics were compared between groups, and multivariable logistic regression was performed.

Results

A total of 1205 patients were identified, 504 before and 701 after the guideline adoption (January 1, 2014). Clinical and pathologic characteristics were similar between time periods. Reexcision rates significantly declined from 21.4 to 15.1 % (p = 0.006) after guideline adoption. A multivariable model identified extensive intraductal component (odds ratio [OR] 2.5, 95 % confidence interval [CI] 1.2–5.2), multifocality (OR 2.0, 95 % CI 1.2–3.6), positive (OR 844.4, 95 % CI 226.3–5562.5) and close (OR 38.3, 95 % CI 21.5–71.8) ductal carcinoma-in situ margin, positive (OR 174.2, 95 % CI 66.2–530.0) and close (OR 6.4, 95 % CI 3.0–13.6) invasive margin, and time period (OR 0.5, 95 % CI 0.3–0.9 for post vs. pre) as independently associated with reexcision.

Conclusions

Overall reexcision rates declined significantly after guideline adoption. Close invasive margins were associated with higher rates of reexcision than negative invasive margins in both time periods; however, the effect diminished in the postguideline adoption period. Thus, we expect continued decline in reexcision rates as adherence to guidelines becomes more uniform.

from Cancer via ola Kala on Inoreader http://ift.tt/2cdGos1
via IFTTT

Impact of Body Mass Index on Clinical Axillary Nodal Assessment in Breast Cancer Patients

Abstract

Background

More than one-third of American adults are obese, and an elevated body mass index (BMI) is postulated to reduce the sensitivity of the clinical evaluation of the axilla. Clinical nodal examination is important in allocating breast cancer patients to appropriate axillary management. This study sought to determine whether BMI influences the rate of nodal positivity in women designated clinically as node-negative (cN0) by physical examination.

Methods

Breast cancer patients deemed cN0 who underwent sentinel lymph node biopsy (SLNB) from February 2006 to December 2011 were identified from a prospectively maintained database. Clinicopathologic features including BMI and axillary surgery results were recorded and compared among pathologically node-negative and node-positive patients.

Results

Overall, 5142 cN0 patients underwent 5262 SLNB procedures during the study period. Nearly one-third of the patients (28 %) were obese (BMI, >30 kg/m²). A positive SLN was identified in 25 % of the patients, and 84 % proceeded to axillary lymph node dissection. Predictors of SLN positivity included younger age, larger tumor size, high nuclear grade, multifocality, and lymphovascular invasion. An increased BMI did not correlate with a higher likelihood of SLN positivity (p = 0.6). The likelihood of cN0 patients having a high burden of axillary metastases (>3 positive nodes) was 4 % overall and, similarly, did not differ according to BMI (p = 0.4).

Conclusion

Elevated BMI was not associated with a higher likelihood of SLN positivity or heavy nodal disease burden among women staged as cN0 by physical exam. These findings indicate that physical examination is appropriate and sufficient for preoperative axillary evaluation of women undergoing initial surgery regardless of patient BMI.

from Cancer via ola Kala on Inoreader http://ift.tt/2bLr1oY
via IFTTT

Editorial: Management Based on Risk: Individualizing the Care of the Breast Cancer Patient

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

Contralateral Prophylactic Mastectomy for Women with T4 Locally Advanced Breast Cancer

Abstract

Background

The use of contralateral prophylactic mastectomy (CPM) for women with unilateral breast cancer is increasing. The authors were interested in assessing whether this trend extended to patients with T4 disease.

Methods

We identified 92 patients from our prospective breast surgery registry with unilateral clinical T4 M0 disease who underwent mastectomy at our institution from October 2008 to July 2015. Patient, tumor, and treatment variables were compared between patients who did and those who did not undergo CPM, and the reasons patients elected CPM were ascertained.

Results

Of the 92 patients, 33 (36 %) underwent a CPM, including 25 of 55 patients (45 %) with inflammatory breast cancer. Immediate breast reconstruction was performed for 11 of the 92 patients (12 %), including 4 CPM patients. Pathology showed benign findings in all 33 CPM cases, including 3 patients with atypical hyperplasia. The primary reason for CPM reported by the patients included fear of occult current or future breast cancer in 12 cases (36 %), symmetry in 11 cases (33 %), avoidance of future chemotherapy in 5 cases (15 %), deleterious BRCA mutation in 2 cases (6 %), contralateral benign breast disease in 2 cases (6 %), and medical oncologist recommendation in 1 cases (3 %). Patients selecting CPM were younger and more likely to have undergone BRCA testing.

Conclusions

A substantial rate of CPM was observed among women undergoing mastectomy for unilateral T4 breast cancer despite the considerable risk of mortality from their index cancer. The reasons for selection of CPM paralleled those reported for patients with early-stage disease. The most common motivation was fear of occult current or future breast cancer and included the desire to avoid further chemotherapy.

from Cancer via ola Kala on Inoreader http://ift.tt/2bLrd7r
via IFTTT

A Novel Treatment Schedule for Rapid Completion of Surgery and Radiation in Early-Stage Breast Cancer

Abstract

Background

Data support the use of accelerated partial-breast irradiation (APBI) for early-stage breast cancer. We initiated a prospective protocol for intraoperative APBI catheter placement using a multi-lumen strut-based device. We hypothesized that with intraoperative pathology assessment of margins and sentinel nodes, all locoregional treatment (surgery and APBI) could be completed within 10 days with acceptable complication rates and cosmesis.

Methods

Eligible patients included women age 50 years or older with clinical T1 estrogen receptor positive (ER+) sentinel lymph node (SLN)-negative invasive ductal cancer or pure ductal carcinoma in situ. Patients were prospectively registered. Cosmesis was assessed using photographs graded independently by three investigators for patients with photos taken 6 months or longer after treatment.

Results

From October 2012 to August 2015, we enrolled 123 patients; 110 (90 %) underwent intraoperative catheter placement, whereas 13 did not due to intraoperative pathology findings. 109 APBI patients (99 %) completed their prescribed radiotherapy within 5 days, and all their locoregional therapy within 9 days, whereas one patient with a delayed positive SLN received only boost radiotherapy via catheter followed by conventional whole breast radiation. The 30-day complication rate was 6 %. In 81 patients with at least one-year followup, complications occurred in 14 (17 %) (including infection in five patients and symptomatic seroma in five patients) and correlated with device size (p = 0.05) but not with tumor size or location. The local recurrence rate was 1.8 % (two patients). Scored cosmesis was excellent or good in 88 % and fair in 12 % of patients.

Conclusions

A protocol for intraoperative strut-based APBI catheter placement using careful patient selection and intraoperative pathology assessment can deliver efficient, effective treatment for early breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2bSnK4E
via IFTTT

Acute and Chronic Complications in Breast Cancer Patients Treated with Intraoperative Radiation Therapy

Abstract

Introduction

Intraoperative radiation therapy (IORT) permits the delivery of radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available about the complications associated with this modality of treatment using the Xoft^® Axxent Electronic Brachytherapy (Axxent) System.

Methods

A total of 702 patients who received IORT using the Xoft^® Axxent System at Hoag Memorial Hospital Presbyterian between June 2010-February 2016 were accrued in an IORT data registry study. The prospective and retrospective protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 3 months, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months.

Results

Acute complications were observed in 21 % of patients and included hematomas that required drainage, seromas requiring drainage more than 3 times, infections treated with antibiotics or surgery, necrosis requiring surgery, and erythema. Chronic complications were observed in 13 % of patients and included seromas, fibrosis, and hyperpigmentation. The majority of acute and chronic problems from IORT were mild. If grade I erythema, fibrosis, and hyperpigmentation were removed, only 32 of 702 (4.6 %) had significant complications. Our complication rates were comparable to those of the TARGIT trial.

Conclusions

IORT is a modality that safely delivers radiation therapy to patients diagnosed with breast cancer. This technique allows women who cannot (or decline to) undergo whole breast radiation to consider breast-conserving therapy rather than mastectomy.

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

Measures of Appropriateness and Value for Breast Surgeons and Their Patients: The American Society of Breast Surgeons Choosing Wisely ® Initiative

Abstract

Background

Current breast cancer care is based on high-level evidence from randomized, controlled trials. Despite these data, there continues to be variability of breast cancer care, including overutilization of some tests and operations. To reduce overutilization, the American Board of Internal Medicine Choosing Wisely ^® Campaign recommends that professional organizations provide patients and providers with a list of care practices that may not be necessary. Shared decision making regarding these services is encouraged.

Methods

The Patient Safety and Quality Committee of the American Society of Breast Surgeons (ASBrS) solicited candidate measures for the Choosing Wisely ^® Campaign. The resulting list of "appropriateness" measures of care was ranked by a modified Delphi appropriateness methodology. The highest-ranked measures were submitted to and later approved by the ASBrS Board of Directors. They are listed below.

Results

(1) Don't routinely order breast magnetic resonance imaging in new breast cancer patients. (2) Don't routinely excise all the lymph nodes beneath the arm in patients having lumpectomy for breast cancer. (3) Don't routinely order specialized tumor gene testing in all new breast cancer patients. (4) Don't routinely reoperate on patients with invasive cancer if the cancer is close to the edge of the excised lumpectomy tissue. (5) Don't routinely perform a double mastectomy in patients who have a single breast with cancer.

Conclusions

The ASBrS list for the Choosing Wisely ^® campaign is easily accessible to breast cancer patients online. These measures provide surgeons and their patients with a starting point for shared decision making regarding potentially unnecessary testing and operations.

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

Oncological and Surgical Outcomes After Nipple-Sparing Mastectomy: Do Incisions Matter?

Abstract

Background

While nipple-sparing mastectomy (NSM) for the treatment of breast cancer is becoming more accepted, technical aspects are still evolving. Data regarding risk factors contributing to complications after NSM are limited. This study evaluated technical aspects on outcomes of NSM.

Methods

Review of our database identified 201 patients who had NSM during the period from January 2012 to June 2015. We compared the effect of operative techniques on surgical outcomes.

Results

A total of 351 NSM were performed in 201 patients. Mean patient age was 47 years. Inframammary (47 %) or periareolar (35 %) incisions were most frequent. Tumescence was used in 203 (58 %) NSM. Skin flaps were created using sharp dissection in 213 (61 %) and electrocautery in 138 (39 %) breasts. Nipple areola complex (NAC) necrosis was seen in 56 (16 %) breasts, of which 7 were severe (2 %). A higher rate of NAC complications was seen with periareolar incisions (p = 0.02). Sharp dissection did not result in significant rates of flap necrosis compared with electrocautery. Ten patients (3 %) had a positive anterior/deep margin, of which 7 (64 %) had an inframammary approach. Twenty-two (11 %) patients had an infection that required intravenous antibiotics. Fourteen (7 %) patients had implant loss. Dissection technique was not associated with implant loss (p = 1.0) or infection (p = 0.84). Forty-two (12 %) patients had radiation and seven (16 %) required implant removal.

Conclusions

NSM has an acceptable complication rate. NAC necrosis requiring excision or implant loss is rare. Postmastectomy radiation is a significant risk factor for implant loss. Inframammary incisions have fewer ischemic complications but may result in tumor-involved margins.

from Cancer via ola Kala on Inoreader http://ift.tt/2bLqFi0
via IFTTT

Complications of Oncoplastic Breast Surgery Involving Soft Tissue Transfer Versus Breast-Conserving Surgery: An Analysis of the NSQIP Database

Abstract

Background

Oncoplastic breast surgery (OBS) aims to provide breast cancer patients with optimum oncologic outcomes and excellent cosmesis. We sought to determine if there is a difference in complications associated with OBS involving soft tissue transfer compared with the traditional breast-conserving surgical (BCS) approach.

Methods

Analysis of the American College of Surgeons National Surgical Quality Improvement Program database was performed. Patients with breast cancer who underwent BCS from 2005 to 2014 were included in the study cohort, while patients undergoing concurrent high-risk non-breast surgery, male patients, and those with metastatic disease were excluded. Patients with concomitant current procedural terminology codes identifying soft tissue transfer were categorized as having OBS. Multivariable analysis was performed to determine the independent effect of OBS on postoperative morbidity.

Results

We identified 75,972 patients who underwent BCS for breast cancer between 2005 and 2014, of whom 1363 (1.8 %) underwent OBS with soft tissue transfer. Compared with the standard lumpectomy group, patients undergoing OBS were more likely to be younger, had a lower body mass index, were less likely to be smokers, and more often received neoadjuvant chemotherapy. OBS with soft tissue transfer also had a significantly longer operative time (83 vs. 59 min; p < 0.001). The multivariable analysis confirmed that soft tissue transfer OBS was not an independent predictor of overall complications (odds ratio 0.78; 95 % confidence interval 0.50–1.19).

Conclusions

These data confirm that the use of OBS with soft tissue transfer for breast cancer treatment does not confer an increased risk of surgical complications, despite the longer operative time. This is important given the increasing use of oncoplastic surgery techniques within North America.

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

Current Trends in the Management of Phyllodes Tumors of the Breast

Abstract

Introduction

National Comprehensive Cancer Network (NCCN) guidelines recommend wide excision without axillary staging to treat phyllodes tumors of the breast. Without prospective trials to guide management, NCCN also recommends consideration of radiation therapy (XRT). We describe current patterns of care for the multidisciplinary management of phyllodes tumors.

Methods

Using Surveillance, Epidemiology, and End Results Program (SEER) data, we identified women diagnosed with phyllodes tumors between 2000 and 2012 who underwent surgical therapy. Trends in breast-conserving surgery (BCS), nodal sampling, and XRT were assessed using the Cochrane–Armitage test. Multivariable logistic regression was used to identify factors associated with treatment.

Results

Of 1238 patients, 56.9 % underwent BCS and 23.6 % underwent nodal sampling (10.5 % after BCS vs. 40.9 % after mastectomy). After surgery, 15.4 % received adjuvant XRT (BCS 12.9 %, and mastectomy 18.8 %). XRT utilization increased significantly over the study period (BCS, p = < 0.0001; mastectomy, p = 0.0003), while nodal sampling did not change significantly. Women were more likely to receive mastectomy if they were older or had larger tumors. Nodal sampling was also associated with older age, larger tumor size, and receipt of mastectomy. Receipt of XRT was associated with later year of diagnosis, larger tumors, and nodal assessment.

Conclusion

Over time, an increasing number of women received XRT after surgical management of phyllodes tumor, and one in four women underwent nodal sampling. While some of this practice can be attributed to concern about more advanced disease in the absence of strong data, there may be an educational gap regarding current guidelines and appropriate management.

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

Current Practices and Barriers to the Integration of Oncoplastic Breast Surgery: A Canadian Perspective

Abstract

Background

Despite the safety and popularity of oncoplastic surgery, there is limited data examining utilization and barriers associated with its incorporation into practice. This study examines the use of oncoplastic techniques in breast conserving surgery and determines the barriers associated with their implementation.

Methods

A 13-item survey was mailed to all registered general surgeons in Ontario, Canada. The survey assessed surgeon demographics, utilization of specific oncoplastic techniques, and perceived barriers.

Results

A total of 234 survey responses were received, representing a response rate of 32.2 % (234 of 725). Of the respondents, 166 surgeons (70.9 %) reported a practice volume of at least 25 % breast surgery. Comparison was made between general surgeons performing oncoplastic breast surgery (N = 79) and those who did not use these techniques (N = 87). Surgeon gender, years in practice, fellowship training, and access to plastic surgery were similar across groups. Both groups rated the importance of breast cosmesis similarly. General surgeons with a practice volume involving >50 % breast surgery were more likely to use oncoplastic techniques (OR 8.82, p < .001) and involve plastic surgeons in breast conserving surgery (OR 2.21, p = .02). For surgeons not performing oncoplastic surgery, a lack of training and access to plastic surgeons were identified as significant barriers. For those using oncoplastic techniques, the absence of specific billing codes was identified as a limiting factor.

Conclusions

Lack of training, access to plastic surgeons, and absence of appropriate reimbursement for these cases are significant barriers to the adoption of oncoplastic techniques.

from Cancer via ola Kala on Inoreader http://ift.tt/2bSnB1d
via IFTTT

Assessing, Counseling, and Treating Patients at High Risk for Breast Cancer

Abstract

Identifying patients at high risk of carrying pathogenic variants in genes is a crucial part of providing both accurate counseling and evidence-based treatment recommendations. Current risk assessment models have strengths and weaknesses that may limit their applicability to specific clinical circumstances. Clinicians must have knowledge regarding variations in available models, how they should be used, and what data they can expect from specific models. In addition, indications for genetic testing are expanding, and the adoption of next-generation sequencing has allowed the creation of multigene testing panels. Complex consequences of panel testing have included an increase in the incidence of identifying variants of uncertain significance and the identification of pathogenic variants in genes for which treatment guidelines are not available. Women diagnosed with breast cancer who carry pathogenic variants in genes with proven associations with breast cancer (BRCA1/2) or highly likely associations (PTEN, PALB2) require additional risk assessment to facilitate treatment decisions that will limit in-breast tumor recurrence and contralateral breast cancer.

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

Utility of Clinical Breast Examinations in Detecting Local–Regional Breast Events After Breast-Conservation in Women with a Personal History of High-Risk Breast Cancer

Abstract

Background

Although breast cancer follow-up guidelines emphasize the importance of clinical examinations, prior studies suggest a small fraction of local–regional events occurring after breast conservation are detected by examination alone. Our objective was to examine how local–regional events are detected in a contemporary, national cohort of high-risk breast cancer survivors.

Methods

A stage-stratified sample of stage II/III breast cancer patients diagnosed in 2006–2007 (n = 11,099) were identified from 1217 facilities within the National Cancer Data Base. Additional data on local–regional and distant breast events, method of event detection, imaging received, and mortality were collected. We further limited the cohort to patients with breast conservation (n = 4854). Summary statistics describe local–regional event rates and detection method.

Results

Local–regional events were detected in 5.5 % (n = 265) of patients. Eighty-three percent were ipsilateral or contralateral in-breast events, and 17 % occurred within ipsilateral lymph nodes. Forty-eight percent of local–regional events were detected on asymptomatic breast imaging, 29 % by patients, and 10 % on clinical examination. Overall, 0.5 % of the 4854 patients had a local–regional event detected on examination. Examinations detected a higher proportion of lymph node events (8/45) compared with in-breast events (18/220). No factors were associated with method of event detection.

Discussion

Clinical examinations, as an adjunct to screening mammography, have a modest effect on local–regional event detection. This contradicts current belief that examinations are a critical adjunct to mammographic screening. These findings can help to streamline follow-up care, potentially improving follow-up efficiency and quality.

from Cancer via ola Kala on Inoreader http://ift.tt/2bSp33x
via IFTTT

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

.


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

Dehydroepiandrosterone inhibits events related with the metastatic process in Breast tumor cell lines

.


from Cancer via ola Kala on Inoreader http://ift.tt/2bTZq3r
via IFTTT

Protonthérapie

Publication date: Available online 24 August 2016
Source:Cancer/Radiothérapie
Author(s): G. Noël, D. Antoni
La protonthérapie est une technique optimisée de radiothérapie. Les améliorations techniques permettent d'obtenir aujourd'hui des machines fiables. Les indications thérapeutiques sont plus claires même si des essais thérapeutiques doivent confirmer les orientations actuelles. Une nouvelle organisation des soins permettra d'encadrer définitivement le nombre de patients pour lequel le traitement sera pertinent. Cette organisation préparera le développement futur de cette technique.Proton therapy is an optimized radiotherapy technique. Today, the technical improvement provides reliable machines. The therapeutic indications are clearer even though therapeutic trials should confirm the current guidelines. A better knowledge in radiobiology could be useful if it is integrated in the treatment planning system. A new organization of care will definitively stabilize the number of patients for which treatment will be relevant. This organization will prepare the future expansion of this technique.



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

Place de la radiothérapie dans la prise en charge des sarcomes rétropéritonéaux

Publication date: Available online 24 August 2016
Source:Cancer/Radiothérapie
Author(s): P. Sargos, E. Stoeckle, B. Henriques de Figueiredo, M. Antoine, M. Delannes, A. Mervoyer, G. Kantor
Dans le traitement des sarcomes rétropéritonéaux, la qualité de la prise en charge initiale (imagerie, biopsie, évaluation préopératoire) conditionne le pronostic. À l'heure actuelle, seule la chirurgie monobloc réalisée dans des centres experts est un standard et aucun traitement périopératoire (chimiothérapie, radiothérapie) ne possède un niveau de preuve suffisant pour justifier d'une attitude en routine. Cependant, la rechute locorégionale constitue le mode d'évolution le plus fréquent de cette maladie. Ainsi, par analogie aux données publiées sur les sarcomes des tissus mous des extrémités, le rôle de la radiothérapie a été évalué, essentiellement de manière rétrospective. Si la radiothérapie adjuvante est de moins en moins pratiquée compte tenu de la toxicité digestive qu'elle engendre, la radiothérapie préopératoire présente de multiples avantages et a fait l'objet d'une étude de phase II (protocole TOMOREP) dont les inclusions sont closes. Une étude européenne de phase III randomisant la radiothérapie, suivie d'une chirurgie (essai de l'European Organization for Research and Treatment of Cancer [EORTC], STRASS), est en cours. L'objectif de cet article est donc de présenter les données concernant l'irradiation préopératoire sur le plan de la dose, des volumes à définir et des techniques à utiliser pour le traitement de cette pathologie rare.The management of retroperitoneal sarcoma can be very challenging, and the quality of initial treatment strategy appears to be a crucial prognostic factor. En bloc surgery is currently the standard of care for these rare tumours and perioperative treatments such as chemotherapy or radiotherapy have not been validated yet. However, local-regional relapse constitutes the most common disease course. While adjuvant radiotherapy is less and less common due to gastrointestinal toxicities, preoperative radiation therapy offers numerous advantages and is being evaluated as part of a national multicentre phase II study (TOMOREP trial) and is the subject of a European randomized phase III study (STRASS trial). The objective of this article is to present data on preoperative irradiation in terms of dose, volumes and optimal radiotherapy techniques for the treatment of this rare disease.



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

Tailored Beta-catenin mutational approach in extra-abdominal sporadic desmoid tumor patients without therapeutic intervention

Abstract

Background

The efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of aggressive fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall aggressive fibromatosis, while adhering to a "watchful waiting" policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor.

Design and methods

GRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall aggressive fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization.

Discussion

This study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression.

Trial registration

The GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number 4714.

from Cancer via ola Kala on Inoreader http://ift.tt/2bl13dH
via IFTTT

MicroRNA-21 regulates prostaglandin E2 signaling pathway by targeting 15-hydroxyprostaglandin dehydrogenase in tongue squamous cell carcinoma

Abstract

Background

Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive forms of head and neck/oral cancer (HNOC), and is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. Identifying the deregulation of microRNA-mRNA regulatory modules (MRMs) is crucial for understanding the role of microRNA in OTSCC.

Methods

A comprehensive bioinformatics analysis was performed to identify MRMs in HNOC by examining the correlation among differentially expressed microRNA and mRNA profiling datasets and integrating with 12 different sequence-based microRNA target prediction algorithms. Confirmation experiments were performed to further assess the correlation among MRMs using OTSCC patient samples and HNOC cell lines. Functional analyses were performed to validate one of the identified MRMs: miR-21-15-Hydroxyprostaglandin Dehydrogenase (HPGD) regulatory module.

Results

Our bioinformatics analysis revealed 53 MRMs that are deregulated in HNOC. Four high confidence MRMs were further defined by confirmation experiments using OTSCC patient samples and HNOC cell lines, including miR-21-HPGD regulatory module. HPGD is a known anti-tumorigenic effecter, and it regulates the tumorigenic actions of Prostaglandin E2 (PGE2) by converts PGE2 to its biologically inactive metabolite. Ectopic transfection of miR-21 reduced the expression of HPGD in OTSCC cell lines, and the direct targeting of the miR-21 to the HPGD mRNA was confirmed using a luciferase reporter gene assay. The PGE2-mediated upregulation of miR-21 was also confirmed which suggested the existence of a positive feed-forward loop that involves miR-21, HPGD and PGE2 in OTSCC cells that contribute to tumorigenesis.

Conclusions

We identified a number of high-confidence MRMs in OTSCC, including miR-21-HPGD regulatory module, which may play an important role in the miR-21-HPGD-PGE2 feed-forward loop that contributes to tumorigenesis.

from Cancer via ola Kala on Inoreader http://ift.tt/2bFu6b5
via IFTTT

The insulin-like growth factor system is modulated by exercise in breast cancer survivors: a systematic review and meta-analysis

Abstract

Background

Insulin-like growth factors (IGF´s) play a crucial role in controlling cancer cell proliferation, differentiation and apoptosis. Exercise has been postulated as an effective intervention in improving cancer-related outcomes and survival, although its effects on IGF´s are not well understood. This meta-analysis aimed to determine the effects of exercise in modulating IGF´s system in breast cancer survivors.

Methods

Databases of PuMed, EMBASE, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, SPORTDiscus, LILACS and Scopus were systematically searched up to November 2014. Effect estimates were calculated through a random-effects model of meta-analysis according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I ² test. Risk of bias and methodological quality were evaluated using the PEDro score.

Results

Five randomized controlled trials (n = 235) were included. Most women were post-menopausal. High-quality and low risk of bias were found (mean PEDro score = 6.2 ± 1). Exercise resulted in significant improvements on IGF-I, IGF-II, IGFBP-I, IGFBP-3, Insulin and Insulin resistance (P < 0.05). Non-significant differences were found for Glucose. Aerobic exercise improved IGF-I, IGFBP-3 and Insulin. No evidence of publication bias was detected by Egger´s test (p = 0.12).

Conclusions

Exercise improved IGF´s in breast cancer survivors. These findings provide novel insight regarding the molecular effects of exercise on tumoral microenvironment, apoptosis and survival in breast cancer survivors.

from Cancer via ola Kala on Inoreader http://ift.tt/2c0YgVR
via IFTTT

Dermatomyositis with anti-TIF-1γ antibodies as a presenting symptom of underlying triple-negative breast cancer: a case report

Abstract

Background

Dermatomyositis is an autoimmune myopathy characterized by proximal muscle weakness, muscle inflammation, and typical skin findings. It is a rare disease with an incidence of ~1/100 000. About 15–30 % of adult-onset cases are caused by underlying malignancy and dermatomyositis can be the first symptom of undiagnosed cancer, mainly in the case of anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies presence. TIF-1γ is a transcriptional cofactor which is implicated in TGFβ signaling pathway that controls cell proliferation, differentiation, apoptosis, and tumorigenesis. Its expression was shown to be associated with younger age, higher tumor grade, more estrogen receptor negativity, tumors larger than 2 cm, and tendency towards poor outcome in early breast cancer. No association between anti-TIF-1γ antibodies and prognosis has been proposed yet.

Case presentation

We report a case of a 43-year-old premenopausal woman presenting with the symptoms of systemic rheumatic disease, the most prominent being a typical skin rash and muscle pain. After a series of investigations, the patient was diagnosed with anti-TIF-1γ positive dermatomyositis and concurrent triple-negative breast cancer (cT1c N3c M0) as an underlying cause. Immediate intravenous corticosteroid therapy relieved the symptoms and enabled anticancer therapy to be commenced. Considering the tumor stage, neoadjuvant therapy with 4 courses of AC (Doxorubicin/Cyclophosphamide) followed by 4 courses of Paclitaxel/Carboplatin was administered. However, no tumor regression was documented and radiotherapy was chosen as the definitive treatment.

Conclusion

Early detection of anti-TIF-1γ autoantibodies can contribute to a rapid diagnosis of tumor-associated dermatomyositis and enable immediate anticancer treatment. We demonstrate the emerging role of anti-TIF-1γ antibodies in the diagnostics of tumor-associated dermatomyositis. Furthermore, we propose a potential role of anti-TIF-1γ antibodies as a prognostic marker in early breast cancer patients.

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

High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer

Abstract

Background

The progression of colorectal cancer (CRC) involves recurrent amplifications/mutations in the epidermal growth factor receptor (EGFR) and downstream signal transducers of the Ras pathway, KRAS and BRAF. Whether genetic events predicted to result in increased and constitutive signaling indeed lead to enhanced biological activity is often unclear and, due to technical challenges, unexplored. Here, we investigated proliferative signaling in CRC using a highly sensitive method for protein detection. The aim of the study was to determine whether multiple changes in proliferative signaling in CRC could be combined and exploited as a "complex biomarker" for diagnostic purposes.

Methods

We used robotized capillary isoelectric focusing as well as conventional immunoblotting for the comprehensive analysis of epidermal growth factor receptor signaling pathways converging on extracellular regulated kinase 1/2 (ERK1/2), AKT, phospholipase Cγ1 (PLCγ1) and c-SRC in normal mucosa compared with CRC stage II and IV. Computational analyses were used to test different activity patterns for the analyzed signal transducers.

Results

Signaling pathways implicated in cell proliferation were differently dysregulated in CRC and, unexpectedly, several were downregulated in disease. Thus, levels of activated ERK1 (pERK1), but not pERK2, decreased in stage II and IV while total ERK1/2 expression remained unaffected. In addition, c-SRC expression was lower in CRC compared with normal tissues and phosphorylation on the activating residue Y418 was not detected. In contrast, PLCγ1 and AKT expression levels were elevated in disease. Immunoblotting of the different signal transducers, run in parallel to capillary isoelectric focusing, showed higher variability and lower sensitivity and resolution. Computational analyses showed that, while individual signaling changes lacked predictive power, using the combination of changes in three signaling components to create a "complex biomarker" allowed with very high accuracy, the correct diagnosis of tissues as either normal or cancerous.

Conclusions

We present techniques that allow rapid and sensitive determination of cancer signaling that can be used to differentiate colorectal cancer from normal tissue.

from Cancer via ola Kala on Inoreader http://ift.tt/2c0Z1yc
via IFTTT

Cancers, Vol. 8, Pages 78: Aberrant Wnt Signaling in Leukemia

The Wnt signaling pathway is essential in the development and homeostasis of blood and immune cells, but its exact role is still controversial and is the subject of intense research. The malignant counterpart of normal hematopoietic cells, leukemic (stem) cells, have hijacked the Wnt pathway for their self-renewal and proliferation. Here we review the multiple ways dysregulated Wnt signaling can contribute to leukemogenesis, both cell autonomously as well as by changes in the microenvironment.

from Cancer via ola Kala on Inoreader http://ift.tt/2bM4KWX
via IFTTT

Invasive ductal carcinoma of the breast with osteoclast-like giant cells and clear cell features: a case report of a novel finding and review of the literature

Abstract

Background

Osteoclast-like giant cells (OLGCs) are a rare histologic finding within a tumor of the breast. Although there has been discussion as to the pathogenesis and prognosis related to this finding, our understanding of its significance remains inconclusive. Clear cells are another unique histologic finding in breast tumors and are typically associated with tumors arising in other organs such as renal cell carcinoma.

Case presentation

This is a case report of a 64-year-old female who presented with one tumor identified as invasive ductal carcinoma with a combination of OLGCs and clear cell features.

Conclusions

To our knowledge, this combination of findings has not been previously described in the literature and therefore represents another morphologic manifestation of breast carcinoma. As patients are diagnosed earlier and live longer, a growing number of these rare variants may be recognized and provide opportunities to further our understanding of the associated molecular pathways which could contribute to the possibility of therapeutic intervention.

from Cancer via ola Kala on Inoreader http://ift.tt/2blm7xP
via IFTTT