Cancer by Sfakianakis Alexandros: 08/04/17

Παρασκευή 4 Αυγούστου 2017

Blocking protein quality control to counter hereditary cancers

Abstract

Inhibitors of molecular chaperones and the ubiquitin-proteasome system have already been clinically implemented to counter certain cancers, including multiple myeloma and mantle cell lymphoma. The efficacy of this treatment relies on genomic alterations in cancer cells causing a proteostatic imbalance, which makes them more dependent on protein quality control (PQC) mechanisms than normal cells. Accordingly, blocking PQC, e.g. by proteasome inhibitors, may cause a lethal proteotoxic crisis in cancer cells, while leaving normal cells unaffected. Evidence, however, suggests that the PQC system operates by following a better-safe-than-sorry principle and is thus prone to target proteins that are only slightly structurally perturbed, but still functional. Accordingly, implementing PQC inhibitors may also, through an entirely different mechanism, hold potential for other cancers. Several inherited cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although they may still retain function. As a consequence of this over-meticulous PQC mechanism, the cell may end up with an insufficient amount of the abnormal, but functional, protein, which in turn leads to a loss-of-function phenotype and manifestation of the disease. Increasing the amounts of such proteins by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes. This article is protected by copyright. All rights reserved.

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Viral cancer therapies: are they ready for combination with other immunotherapies?

Future Oncology, Ahead of Print.

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Cancer stem cell research in Iran: potentials and challenges

Future Oncology, Ahead of Print.

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Local therapy for triple-negative breast cancer: a comprehensive review

Future Oncology, Ahead of Print.

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Serum metabolomics can predict the outcome of first systematic transrectal prostate biopsy in patients with PSA

Future Oncology, Ahead of Print.

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Treatment of adult acute lymphoblastic leukemia with inotuzumab ozogamicin

Future Oncology, Ahead of Print.

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Are peptide vaccines viable in combination with other cancer immunotherapies?

Future Oncology, Ahead of Print.

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Immunomodulatory effects of current cancer treatment and the consequences for follow-up immunotherapeutics

Future Oncology, Ahead of Print.

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The importance for immunoregulation for long-term cancer control

Future Oncology, Ahead of Print.

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“Is immunotherapy a viable option in treating mesothelioma?”

Future Oncology, Ahead of Print.

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Cancer pain management: recommendations from a Latin-American experts panel

Future Oncology, Ahead of Print.

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Four PTEN-targeting co-expressed miRNAs and ACTN4-targeting miR-548b are independent prognostic biomarkers in human squamous cell carcinoma of the oral tongue

Abstract

The purpose of this study was to determine the prognostic value and oncogenic pathways associated to miRNA expression in squamous cell carcinoma of the oral tongue and to link these miRNA candidates with potential gene targets. We performed a miRNA screening within our institutional cohort (n = 58 patients) and reported five prognostic targets including a cluster of four co-expressed miRNAs (miR-18a, miR-92a, miR-103, and miR-205). Multivariate analysis showed that expression of miR-548b (p = 0.007) and miR-18a (p = 0.004, representative of co-expressed miRNAs) are independent prognostic markers for squamous cell carcinoma of the oral tongue. These findings were validated in The Cancer Genome Atlas (TCGA) cohort (n=131) for both miRNAs (miR-548b: p = 0.027; miR-18a: p = 0.001). Bioinformatics analysis identified PTEN and ACTN4 as direct targets of the four co-expressed miRNAs and miR-548b, respectively. Correlations between the five identified miRNAs and their respective targeted genes were validated in the two merged cohorts and were concordantly significant (miR-18a/PTEN: p < 0.0001; miR-92a/PTEN: p = 0.0008; miR-103/PTEN: p = 0.008; miR-203/PTEN: p = 0.019; miR-548b/ACTN4: p = 0.009). This article is protected by copyright. All rights reserved.

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Sink or Collaborate: How the Immersive Model Has Helped Address Typical Adolescent and Young Adult Barriers at a Single Institution and Kept the Adolescent and Young Adult Program Afloat

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.

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TARGETING RNA-POLYMERASE I IN BOTH CHEMOSENSITIVE AND CHEMORESISTANT POPULATIONS IN EPITHELIAL OVARIAN CANCER

Purpose: A hallmark of neoplasia is increased ribosome biogenesis, and targeting this process with RNA polymerase I (Pol I) inhibitors has shown some efficacy. We examined the contribution and potential targeting of ribosomal machinery in chemotherapy resistant and sensitive models of ovarian cancer. Experimental Design: Pol I machinery expression was examined, and subsequently targeted with the Pol I inhibitor CX-5461, in ovarian cancer cell lines, an immortalized surface epithelial line, and patient derived xenograft (PDX) models with and without chemotherapy. Effects on viability, Pol I occupancy of rDNA, ribosomal content, and chemosensitivity were examined. Results: In PDX models, ribosomal machinery components were increased in chemotherapy-treated tumors compared to controls. 13 cell lines were sensitive to CX-5461, with IC50s 25nM - 2μM. Interestingly two chemoresistant lines were 10.5- and 5.5-fold more sensitive than parental lines . CX-5461 induced DNA damage checkpoint activation and G2/M arrest with increased H2AX staining. Chemoresistant cells had 2-4-fold increased rDNA Pol I occupancy and increased rRNA synthesis, despite having slower proliferation rates, while ribosome abundance and translational efficiency were not impaired. In five PDX models treated with CX-5461, one showed a complete response, one a 55% reduction in tumor volume, and one maintained stable disease for 45 days. Conclusions: Pol I inhibition with CX-5461 shows high activity in ovarian cancer cell lines and PDX models, with an enhanced effect on chemoresistant cells. Effects occur independent of proliferation rates or dormancy. This represents a novel therapeutic approach that may have preferential activity in chemoresistant populations.

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Randomized Controlled Trials in Soft Tissue Sarcoma: We Are Getting There!

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): Andrea J. MacNeill, Abha Gupta, Carol J. Swallow

Teaser

Soft tissue sarcoma (STS) is a family of malignancies for which individual management decisions can be complex. There is a paucity of level 1 evidence, as the rarity and heterogeneity of STS pose challenges to the design and execution of randomized controlled trials. Radiotherapy (RT) is routinely used to facilitate function-preserving surgery and to improve local control. Delivery of RT in the preoperative setting can decrease chronic toxicities at the cost of increased wound complications in the short-term. The role of adjuvant systemic therapies remains controversial in adult STS.

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An Update on Randomized Clinical Trials in Metastatic Colorectal Carcinoma

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): Naruhiko Ikoma, Kanwal Raghav, George Chang

Teaser

There have been remarkable advances in the treatment of metastatic colorectal cancer over the past 20 years, chiefly achieved by development of new active drugs and establishment of effective systemic therapy regimens. Multidisciplinary care of resectable liver disease with use of perioperative systemic therapy and superior liver resection has resulted in prolonged survival of select patients. Median overall survival has significantly improved with the modern multiagent regimens. This article reviews recent high-quality randomized clinical trials that were conducted to address optimal treatment of advanced and metastatic colorectal carcinoma, mainly focused on initially inoperable metastatic disease.

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Randomized Clinical Trials in Pancreatic Cancer

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): Neha Goel, Sanjay S. Reddy

Teaser

The management of pancreatic cancer has grown rapidly in the last decade. The Gastrointestinal Tumor Study Group trial in 1985 supported postoperative chemoradiation, and a more recent study recommended 6 months of adjuvant gemcitabine and capecitabine or monotherapy with gemcitabine or fluorouracil plus folinic acid, in the absence of neoadjuvant therapy. Clinicians are now studying the role of targeted therapy in pancreatic cancer and neoadjuvant chemotherapy in resectable, borderline resectable, and locally advanced pancreatic cancer. This article critically evaluates the evolution of pancreatic cancer management, focussing on level 1a, prospective randomized control trials from 2007 to 2017.

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Randomized Controlled Trials in Neuroendocrine Tumors

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): John C. McAuliffe, Edward M. Wolin

Teaser

Understanding of neuroendocrine tumors has increased greatly in the last 2 decades. Along with this, the prevalence of neuroendocrine tumors has increased because of the ubiquitous use of cross-sectional imaging, improved endoscopic screening, and the indolent nature of the disease. Up to 35% of patients have symptoms at the time of diagnosis, whereas the others have occult disease. Neuroendocrine tumors are a diverse group of malignancies with unique clinical courses. This article critically reviews the most important randomized controlled trials for neuroendocrine tumors and introduces a few awaiting completion.

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Advancing Treatment Approach to the Older Patient with Cancer Through Clinical Trials Participation

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): Efrat Dotan

Teaser

The aging of the population worldwide brings a "Tsunami" of older patients to oncology practices. Oncologists are faced with determining the fitness of patients for therapy and tailoring appropriate therapy. Ongoing treatment of this patient population is challenging because of physiologic changes of aging, comorbidities, and various geriatric syndromes. Underrepresentation of older patients in clinical trials results in a gap in knowledge and lack of clear evidence to guide treatment approach. In recent years, some advancements have been made with publication of elderly specific studies. However, much remains to be done by the oncologic community to continue and invest in these research efforts and expand the knowledge base in this arena.

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An Update on Randomized Clinical Trials in Hepatocellular Carcinoma

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): Hao-Wen Sim, Jennifer Knox, Laura A. Dawson

Teaser

Hepatocellular carcinoma is a common malignancy that typically occurs in the setting of comorbid liver disease. Optimal management is challenging, especially given the assortment of available treatment modalities. This article reviews the randomized clinical trials that have formed the basis of contemporary hepatocellular carcinoma management.

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Randomized Clinical Trials in Gastrointestinal Stromal Tumors

Publication date: Available online 4 August 2017
Source:Surgical Oncology Clinics of North America
Author(s): Yang Liu, Margaret von Mehren

Teaser

This review explores the current standard of care for the surgical management of gastrointestinal stromal tumors, highlights important studies in the medical management of gastrointestinal stromal tumors, and provides guidance in how these studies changed the standard of care in clinical practice.

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Role of glial-cell-derived neurotrophic factor in salivary gland stem cell response to irradiation

Recently, stem cell therapy has been proposed to allow regeneration of radiation damaged salivary glands. It has been suggested that glial-cell-derived neurotrophic factor (GDNF) promotes survival of mice salivary gland stem cells (mSGSCs). The purpose of this study was to investigate the role of GDNF in the modulation of mSGSC response to irradiation and subsequent salivary gland regeneration.

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Radiosensitization by gold nanoparticles: Will they ever make it to the clinic?

The utilization of gold nanoparticles (AuNPs) as radiosensitizers has shown great promise in pre-clinical research. In the current review, the physical, chemical, and biological pathways via which AuNPs enhance the effects of radiation are presented and discussed. In particular, the impact of AuNPs on the 5 Rs in radiobiology, namely repair, reoxygenation, redistribution, repopulation, and intrinsic radiosensitivity, which determine the extent of radiation enhancement effects are elucidated. Key findings from previous studies are outlined.

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Carbon-ion re-irradiation for recurrences after initial treatment of stage I non-small cell lung cancer with carbon-ion radiotherapy

To investigate carbon-ion radiotherapy (CIRT) for in-field recurrence of stage I non-small cell lung cancer (NSCLC) initially treated with CIRT.

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Educational and vocational goal disruption in adolescent and young adult cancer survivors

Abstract

Objective

Cancer in adolescents and young adults (AYAs) can interrupt important developmental milestones. Absence from school and time lost from work, together with the physical impacts of treatment on energy and cognition, can disrupt educational and vocational goals. The purpose of this paper is to report on AYA cancer survivors' experiences of reintegration into school and/or work and to describe perceived changes in their educational and vocational goals.

Methods

AYAs recruited from seven hospitals in Australia, aged 15-26years and ≤24months post-treatment, were interviewed using the Psychosocial Adjustment to Illness Scale (PAIS). Responses were analysed to determine the extent of, and explanations for, cancer's effect on school/work.

Results

Forty-two AYA cancer survivors (50%female) participated. Compared with their previous vocational functioning, 12(28.6%) were scored as experiencing mild impairment, 14(33.3%) moderate impairment, and 3(7.1%) marked impairment. AYAs described difficulties reintegrating to school/work as a result of cognitive impacts such as concentration problems and physical impacts of their treatment, including fatigue. Despite these reported difficulties, the majority indicated that their vocation goals were of equal or greater importance than before diagnosis (26/42;62%), and most AYAs did not see their performance as compromised (23/42;55%). Many survivors described a positive shift in life goals and priorities. The theme of goal conflict emerged where AYAs reported compromised abilities to achieve their goals.

Conclusions

The physical and cognitive impacts of treatment can make returning to school/work challenging for AYA cancer survivors. AYAs experiencing difficulties may benefit from additional supports to facilitate meaningful engagement with their chosen educational/vocational goals.

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Congenital cystic adenomatoid malformation – dangers of misdiagnosis: a case report

Congenital cystic adenomatoid malformation is a rare pulmonary malformation, but is the most common lung malformation observed in children. In developing countries, such as Morocco, prenatal diagnosis is missi...

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In Melanoma, Personalized Treatment Vaccines Show Promise

Results of an early-phase trial showed that a treatment vaccine personalized to a specific patient's cancer generated a robust immune response against the cancer and may have helped to prevent it from returning.

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Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation

Approximately 5% of unselected patients with breast cancer carry a germline BRCA mutation. Such mutations are more likely to be present in patients who have a strong family history of breast cancer, younger patients, patients who have triple-negative (i.e. human epidermal growth factor receptor…

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Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation

Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study

Abstract

Background

Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC.

Methods

A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included.

Results

Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival.

Conclusions

Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.

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A novel CBCT-based method for derivation of CTV-PTV margins for prostate and pelvic lymph nodes treated with stereotactic ablative radiotherapy

Traditional CTV-PTV margin recipes are not generally applicable in the situation of stereotactic ablative radiotherapy (SABR) treatments of multiple target volumes with a single isocentre. In this work, we pre...

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Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer

Abstract

Background

Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences.

Methods

The entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins.

Results

Among 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates.

Conclusions

Among the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome.

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Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization

Abstract

Introduction

Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D.

Methods

Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined.

Results

Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs.

Conclusions

US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden.

Funding

Sanofi US, Inc.

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A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia

Publication date: Available online 3 August 2017
Source:Cancer Genetics
Author(s): Matthew J. Oberley, Christopher Denton, Jianling Ji, Matthew Hiemenz, Deepa Bhojwani, Dejerianne Ostrow, Samuel Wu, Paul Gaynon, Gordana Raca
The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia. We describe identification of a FIP1L1-PDGFRA fusion in a 13-year-old boy who presented with T-lymphoblastic leukemia/lymphoma without eosinophilia. Detection of FIP1L1- PDGFRA driven neoplasms at diagnosis is usually critical for proper treatment, since almost all reported cases responded to tyrosine kinase inhibitors. However, our patient's leukemia was refractory to standard chemotherapy, and did not show a meaningful response to tyrosine kinase inhibitor therapy. Testing for a FIP1L1- PDGFRA rearrangement is at present limited to patients with idiopathic hypereosinophilia, and we hypothesize that this abnormality may be under-diagnosed in children with acute leukemias.

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Do we still need IQ-scores? Misleading interpretations of neurocognitive outcome in pediatric patients with medulloblastoma: a retrospective study

Abstract

Over the past decades, many studies used global outcome measures like the IQ when reporting cognitive outcome of pediatric brain tumor patients, assuming that intelligence is a singular and homogeneous construct. In contrast, especially in clinical neuropsychology, the assessment and interpretation of distinct neurocognitive domains emerged as standard. By definition, the full scale IQ (FIQ) is a score attempting to measure intelligence. It is established by calculating the average performance of a number of subtests. Therefore, FIQ depends on the subtests that are used and the influence neurocognitive functions have on these performances. Consequently, the present study investigated the impact of neuropsychological domains on the singular "g-factor" concept and analysed the consequences for interpretation of clinical outcome. The sample consisted of 37 pediatric patients with medulloblastoma, assessed 0–3 years after diagnosis with the Wechsler Intelligence Scales. Information processing speed and visuomotor function were measured by the Trailmaking Test, Form A. Our findings indicate that FIQ was considerably impacted by processing speed and visuomotor coordination, which leaded to an underestimation of the general cognitive performance of many patients. One year after diagnosis, when patients showed the largest norm-deviation, this effect seemed to be at its peak. As already recommended in international guidelines, a comprehensive neuropsychological test battery is necessary to fully understand cognitive outcome. If IQ-tests are used, a detailed subtest analysis with respect to the impact of processing speed seems essential. Otherwise patients may be at risk for wrong decision making, especially in educational guidance.

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Editorial Board

Publication date: August 2017
Source:Cancer/Radiothérapie, Volume 21, Issue 5

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Issue Contents

Publication date: August 2017
Source:Cancer/Radiothérapie, Volume 21, Issue 5

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Gankyrin induces STAT3 activation in tumour microenvironment and sorafenib resistance in hepatocellular carcinoma

Abstract

Most hepatocellular carcinomas (HCCs) develop as a result of chronic liver inflammation. We have shown that the oncoprotein gankyrin is critical for inflammation-induced tumourigenesis in the colon. Although the in vitro function of gankyrin is well known, its role in vivo remains to be elucidated. We investigated the effect of gankyrin in tumour microenvironment of mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrin^f/f) and gankyrin deletion both in liver parenchymal and non-parenchymal cells (Mx1-Cre;gankyrin^f/f). Gankyrin upregulates VEGF expression in tumor cells. Gankyrin binds to Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), mainly expressed in liver non-parenchymal cells, resulting in phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3). Gankyrin deficiency in non-parenchymal cells, but not in parenchymal cells, reduced STAT3 activity, interleukin (IL)-6 production, and cancer stem cell marker (Bmi1 and epithelial cell adhesion molecule [EpCAM]) expression, leading to attenuated tumourigenic potential. Chronic inflammation enhances gankyrin expression in the human liver. Gankyrin expression in the tumour microenvironment is negatively correlated with progression-free survival in patients undergoing sorafenib treatment for HCC. Thus, gankyrin appears to play a critical oncogenic function in tumour microenvironment and may be a potential target for developing therapeutic and preventive strategies against HCC.

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Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma

Abstract

Purpose

This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m²) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m² (CP), nidaplatinum 80 mg/m² (NP), lobaplatin 35 mg/m² (LP), and oxaliplatin 135 mg m² (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months.

Results

No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors.

Conclusion

Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy.

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Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusion

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Local protocol variations for Image-Guided Radiotherapy in the multicenter Dutch hypofractionation (HYPRO) trial: impact of rectal balloon and MRI delineation on anorectal dose and gastrointestinal toxicity levels

Publication date: Available online 3 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): R.C. Wortel, W.D. Heemsbergen, R.J. Smeenk, M.G. Witte, A.D.G. Krol, F.J. Pos, L. Incrocci
PurposeThe phase 3 XXX trial randomized intermediate to high-risk localized prostate cancer patients to conventionally fractionated (78Gy/39fr) or hypofractionated radiotherapy (64.6Gy/19fr). Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers.Methods and MaterialsFrom the trial population we selected patients (n=572) from four treatment centers who received image-guided-IMRT (IG-IMRT). Center A (n=242) applied planning target volume (PTV) margins of 5-6mm and was considered the reference center. In center B (n=170, 7mm margins), magnetic resonance imaging (MRI) was integrated in treatment planning. An endorectal balloon (ERB) was applied in center C (n=85, 7mm margins). Center D (n=75) applied the largest PTV-margins of 8mm. The study protocol provided identical anorectal dose constraints and local protocols were applied for further treatment optimization. Anorectal dose-surface histograms were compared applying t-tests. Rectal complaints during follow-up (6 months-4 years) were compared in a generalized linear model, adjusting for age, follow-up, treatment arm, and hormone therapy.ResultsFavorable anorectal dose distributions were found for center B (MRI delineation) and C (ERB application) as compared to center A and D. This was associated with significantly lower incidences of patient-reported complaints of rectal incontinence, use of incontinence pads, and rectal discomfort in these centers. Furthermore, lower incidences of increased stool frequency (≥4/day) and mucous loss were observed for center C.ConclusionsDespite comparable IG-IMRT techniques and predefined dose constraints, pronounced differences in dose distributions and toxicity rates were observed. MRI delineation and ERB application were associated with favorable rectal dose parameters and toxicity profiles, whereas a 2-3mm difference in PTV-margins did not translate into observed differences. We conclude that choices for treatment optimization of IG-IMRT are important and clinically relevant for patients since these affect symptoms experienced in daily life.

Teaser

The effects of differences in techniques and treatment protocols on patient-reported rectal toxicity were compared between treatment centers participating in the prospective prostate XXX trial. All included centers applied image-guided-IMRT using identical anorectal dose constraints. As compared to reference center A (5-6mm PTV margins), favorable anorectal dose distributions were found for center B (MRI delineation, 7mm margins) and center C (endorectal balloon application, 7mm margins). This translated into significantly lower incidences of rectal complaints within both centers.

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Hypofractionated nodal radiation therapy for breast cancer was not associated with increased patient-reported arm or brachial plexopathy symptoms

Publication date: Available online 3 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nelson Leong, Pauline T. Truong, Keith Tankel, Winkle Kwan, Lorna Weir, Ivo A. Olivotto
PurposeTo determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25-2.5 Gy/fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx.Materials and MethodsTwo cancer registries were used to identify subjects who received CT-planned, nodal RT for pT1-3, pN0-2, M0 breast cancer from 2007-2010 at two cancer institutions. Following ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale (SASS), a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living (ADL). Clinico-pathologic characteristics and SASS scores were compared between HF/CF cohorts using non-parametric analysis, chi-squared analysis and multivariate ordinal regression.Results800/1759 patients returned a completed survey (45.5%). 708 eligible cases formed the study cohort. 406 (57%) received HFRT (40 Gy/16fx, 45 Gy/20fx), and 302 (43%) received CFRT (45-50 Gy/25fx, 50.4 Gy/28fx). Median time interval post-RT was 5.7 years. 43% and 75% of patients received breast conserving surgery and chemotherapy respectively. 22% received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (p<0.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (p=0.44), as were the mean sums of responses in arm symptoms (p=0.17) and ADL (p=0.85). HF patients reported lower rates of shoulder stiffness (p=0.04), trouble moving the arm (p=0.02), and ability to reach overhead (p<0.01) compared to the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy.ConclusionsNodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared to CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

Teaser

Among 708 women treated with CT-planned regional nodal radiation therapy (RT) for breast cancer, self-reported arm symptoms were similar or less debilitating following modestly hypofractionated (2.25-2.5 Gy/day) versus conventionally fractionated (≤ 2 Gy/day) RT at a median of 5.7 years after treatment.

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Complementary and Alternative Medicine and Their Effect on Global Health

By Nathan Douthit

According to the World Health Organization (WHO), the use of complementary and alternative medicine (CAM) is on the rise. The US National Institute of Health defines complementary medicine as non-mainstream, non-western practice used together with conventional medicine, whereas alternative medicine is defined as the same used instead of conventional medicine. The WHO also offers a definition of traditional medicine (TM) as

"the sum total of the knowledge, skill, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness"

Globally, TM and CAM are much more accessible to patients than conventional medicine. Therefore the WHO strategy for TM and CAM revolves around research into these alternative techniques as well as education and training for their practice. However, recent years have seen a surge in popularity for CAM in western countries as well, with many being willing to pay out of pocket for these treatments. Integration of these practices into national health systems can allow them to be regulated and safely practiced along with conventional medicine for the best possible outcomes.

Unfortunately, the case report "Consequences of delivery at home in a woman without prenatal care" by Kumar et al reveals the danger associated with lack of education, training and regulation. We are told,

"The patient denied having any allopathic prenatal care during the current pregnancy. She denied having gestational diabetes testing, blood work or detailed ultrasonography, but she stated that she had undergone regular Doppler and bedside ultrasound scans by her midwife."

Despite having had three prior caesarean sections, the woman chose a direct entry midwife, defined as follows.

"Direct entry midwives are defined as independent practitioners educated in midwifery through self-study, apprenticeship, a mid- wifery school or a university-based programme…. In the USA, licensure and training varies per state, with ∼50% of states not requiring licensure for direct entry midwives. Most patients are unaware of the difference between [direct entry and certified nurse midwives] and may not receive the necessary guidance to choose the appropriate provider for their needs."

This patient's past medical history puts her at increased risk, and her poor outcome is the result of lack of education, regulation and information in this alternative delivery.

BMJ Case Reports invites authors to publish cases regarding the effects both positive and negative of complementary and alternative medicine. Global health case reports can emphasize:

-Successful integration of CAM into national health systems

-Research on CAM that has proved useful in patient care

-Partnerships between practitioners of CAM and practitioners of conventional medicine that have improved patient outcomes

-Use of CAM causing delays in care, inappropriate care or worsening of patient outcomes.

Manuscripts may be submitted by students, physicians, nurses or other medical professionals to BMJ Case Reports. For more information, review the blog on how to write a global health case report.

Failure modes and effects analysis of total skin electron irradiation technique

Abstract

Purpose

Total skin electron irradiation (TSEI) is a radiotherapy technique which consists of an homogeneous body surface irradiation by electrons. This treatment requires very strict technical and dosimetric conditions, requiring the implementation of multiple controls. Recently, the Task Group 100 report of the AAPM has recommended adapting the quality assurance program of the facility to the risks of their processes.

Materials and methods

A multidisciplinary team evaluated the potential failure modes (FMs) of every process step, regardless of the management tools applied in the installation. For every FM, occurrence (O), severity (S) and detectability (D) by consensus was evaluated, which resulted in the risk priority number (RPN), which permitted the ranking of the FMs. Subsequently, all the management tools used, related to the TSEI process, were examined and the FMs were reevaluated, to analyze the effectiveness of these tools and to propose new management tools to cover the greater risk FMs.

Results

361 FMs were identified, 103 of which had RPN ≥80, initially, and 41 had S ≥ 8. Taking this into account the quality management tools FMs were reevaluated and only 30 FMs had RPN ≥80. The study of these 30 FMs emphasized that the FMs that involved greater risk were related to the diffuser screen placement and the patient's position during treatment.

Conclusions

The quality assurance program of the facility has been adapted to the risk of this treatment process, following the guidelines proposed by the TG-100. However, clinical experience continually reveals new FMs, so the need for periodic risk analysis is required.

http://ift.tt/2wseH3k

Failure modes and effects analysis of total skin electron irradiation technique

Abstract

Purpose

Materials and methods

Results

Conclusions

http://ift.tt/2wseH3k

Scientists estimate number of U.S. women living with metastatic breast cancer

http://ift.tt/2wrV23L

Active surveillance helps prostate cancer patients keep quality of life, findings show

http://ift.tt/2wrPZ36

Issue Information – TOC

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Long-term antibiotic use associated with cancer-causing polyps

http://ift.tt/2vzm5Ok

Ultrasound assessment of the bowel: inflammatory bowel disease and conditions beyond

Abstract

Ultrasound (US) is a versatile imaging study for the evaluation of the bowel in children. US imaging of the bowel can be used as the initial examination or in follow-up for many common pediatric diseases. In this article, we highlight our bowel US technique and describe how US can depict the features of a select group of bowel pathologies relevant to pediatric practice.

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Introduction: Pediatric ultrasound

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Clinical and sonographic features of pediatric soft-tissue vascular anomalies part 1: classification, sonographic approach and vascular tumors

Abstract

Sonography can be used in the management of pediatric soft-tissue vascular anomalies for diagnosing, for assessing lesion extent and for evaluating complications and response to therapy. The sonographic technique includes a combination of gray-scale imaging with color and spectral Doppler techniques. However the interpretation of the sonographic findings requires correlation with the clinical findings, some of which can be easily obtained at the time of scanning. This has to be combined with the use of appropriate nomenclature and the most updated classification in order to categorize these children into the appropriate management pathway. In this article, which is part 1 of a two-part series, the authors review the current classification of vascular anomalies, provide a clinical and a sonographic approach to these lesions, and review the most relevant clinical and sonographic features of vascular tumors including infantile and congenital hemangiomas, tufted angioma, kaposiform hemangioendothelioma, pyogenic granuloma, intramuscular capillary-type hemangioma and angiosarcoma.

http://ift.tt/2v3nzyE

Lower-extremity venous ultrasound — past, present and future

Abstract

Deep vein thrombosis is a frequent clinical concern and imaging request in the pediatric population. There has been increased awareness of deep venous thrombosis in the pediatric population and sonography is now utilized more liberally and frequently to evaluate for thrombosis in the extremities. In this review the author discusses various aspects of deep vein thrombosis in the lower extremity including the pathophysiology, background, and morbidity in children. The current ultrasound guidelines and techniques, and the controversy over treatment are discussed as well.

http://ift.tt/2we9Q6M

Hip ultrasonography in clinical practice

Abstract

The current practice of hip ultrasonography for developmental dysplasia of the hip (DDH) is based on more than three decades of experience. During this time, professional medical organizations in the United States have addressed both the clinical practice and imaging aspects of early detection of DDH. Current evidence-based clinical practice recommendations come from the American Academy of Pediatrics and the American Academy of Orthopaedic Surgeons. Consensus imaging recommendations come from the American Institute of Ultrasound in Medicine, the American College of Radiology, Society for Pediatric Radiology and the Society of Radiologists in Ultrasound. In this review the author compares and contrasts the current guidelines and offers additional practice tips for those providing comprehensive hip ultrasound services to infants.

http://ift.tt/2v3Qums

Sonography of pediatric superficial lumps and bumps: illustrative examples from head to toe

Abstract

Superficial lumps and bumps are extremely common in children, and the vast majority ultimately prove to be benign. Duplex/color Doppler ultrasound (US) has emerged as the first-line imaging modality for the evaluation of these superficial pediatric masses because it provides a means for rapid acquisition of information including size, shape, location, internal content and vascularity. More important, it does so without utilizing radiation, iodinated contrast material or sedation/anesthesia. In this review, we present the sonographic findings of a variety of cases ranging from head to toe that are either uncommonly seen or were diagnosed in an atypical fashion (i.e. ultrasound). In situations where the lesion is too deep, hyperechoic or large to be fully assessed within the field of view or if malignancy is suspected, then additional cross-sectional imaging is warranted for further evaluation.

http://ift.tt/2wdnxmh

Intussusception: past, present and future

Abstract

Intussusception is a common etiology of acute abdominal pain in children. Over the last 70 years, there have been significant changes in how we diagnose and treat intussusception, with a more recent focus on the role of ultrasound. In this article we discuss historical and current approaches to intussusception, with an emphasis on ultrasound as a diagnostic and therapeutic modality.

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Urinary tract dilation illustrations: reply to Phelps et al .

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Classification of pediatric urinary tract dilation: the new language

Abstract

The multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system) was created to unify the language used to describe urinary tract dilation on antenatal and postnatal ultrasound examinations and thereby facilitate communication among providers and improve outcomes research. The background and new classification system are described in this review, with imaging examples.

http://ift.tt/2v3nyL6

Hermes

http://ift.tt/2we9Nb6

Ultrasound of congenital and inherited disorders of the pediatric hepatobiliary system, pancreas and spleen

Abstract

Ultrasound is often the initial imaging examination performed of the solid organs of the pediatric abdomen. The sonographic appearance of the hepatobiliary system, pancreas and spleen changes with growth and development. This article reviews the normal US appearance of these organs in children and illustrates, through case examples, congenital and inherited conditions that affect them.

http://ift.tt/2v3ntah

Ultrasound imaging of renin-mediated hypertension

Abstract

The incidence of primary (i.e. essential) hypertension in children and adolescents is increasing; however, secondary hypertension, with an identifiable cause, remains relatively common and might be treatable or even curable. Renovascular hypertension is an uncommon but important secondary cause of hypertension in the pediatric population that can be associated with substantial morbidity. In this article we discuss renin-mediated causes of hypertension in children and related complications, review renal Doppler ultrasound techniques for the evaluation of renin-mediated hypertension (including both direct and indirect assessments), and briefly appraise the literature pertaining to renal Doppler ultrasound and the assessment of pediatric hypertension. Finally, we describe a proposed role for renal Doppler ultrasound in the workup of suspected renin-mediated hypertension in children and adolescents.

http://ift.tt/2wdHpFZ

Ultrasound of the pediatric appendix

Abstract

Appendicitis is the most common pediatric surgical emergency. Ultrasound (US) receives the highest appropriate rating scale in children with right lower quadrant pain suspected to have appendicitis. The US exam of the appendix has improved since Puylaert pioneered the technique of graded compression in 1986. In this article, we review ultrasonography of the pediatric appendix as it pertains to the normal appendix, acute appendicitis and the different sonographic manifestations. We also briefly describe technical optimization of image acquisition, common pitfalls and differential diagnoses.

http://ift.tt/2v2S1sG

Pediatric Radiology continuing medical education activity

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Urinary tract dilation illustrations

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Ultrasound imaging of synovial inflammation in juvenile idiopathic arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is the most common rheumatic entity of childhood. The hallmark feature of all subtypes is joint inflammation. Imaging is used to evaluate the extent and severity of inflammation, degree of joint damage and response to treatment, which in turn impacts patient management. Ultrasound has become a useful adjunct to clinical examination because it shows promise in evaluating clinical and subclinical inflammation (synovitis, enthesitis) as well as cartilage and bone erosive changes. However more collaborative research is needed to help define the normal appearance of the growing skeleton, clarify the significance of subclinical findings and develop useful definitions, imaging protocols and scoring systems of disease.

http://ift.tt/2wdHoSr

Pediatric scrotal ultrasound: review and update

Abstract

In this pictorial essay the authors review the normal sonographic gray-scale and Doppler appearance of the pediatric scrotum with an emphasis on technique. The authors present an update on ultrasound diagnosis and outcomes in testicular torsion and differentiation from other acute scrotal processes, as well as sonographic imaging of testicular microlithiasis and uncommon or atypical scrotal masses including splenogonadal fusion, polyorchidism, meconium peritonitis and epidermoid cyst. Further, the authors discuss testicular neoplasms in the context of testicular microlithiasis.

http://ift.tt/2v32ww3

Sonographic spinal imaging of normal anatomy, pathology and magnetic growing rods in children

Abstract

The wide availability of ultrasound, along with its lack of ionizing radiation burden and need for sedation for most exams, often make sonography the first line in the imaging evaluation of children. The developing osseous anatomy of the spine in young infants provides a distinct window allowing for a detailed depiction of the spinal canal and its contents, which is not present in older children or adults. Here we review the clinical indications, sonographic technique, normal anatomy and pathology for imaging the lumbosacral spine in neonates and young infants. Additionally, we review the procedure for ultrasound assessment of the lengthening of magnetically controlled growing spinal rods, which allows orthopedists and radiologists to evaluate the effectiveness of distraction procedures of this hardware without the use of ionizing radiation.

http://ift.tt/2wdUPBY

Continuous low plasma concentrations of everolimus provides equivalent efficacy to oral daily dosing in mouse xenograft models of human cancer

Abstract

Purpose

Everolimus is a drug used successfully in a number of different oncology indications, but significant on-target toxicities exist. We explored the possibility of improving the therapeutic index (TI) by studying alternative means of administering the drug based upon low continuous dosing.

Methods

All studies were performed using naïve nude mice or nude mice bearing s.c. human renal 786-O tumours or human breast MDA-MB-468 tumours. Everolimus was administered via a standard emulsion, either i.v., p.o., i.p., s.c., or via s.c. osmotic mini-pumps (MP) or via poly-lactic-co-glycolic (PLGA)-microparticles (PLGA-µP) prepared from everolimus powder injected s.c. Total-drug levels in blood, plasma or tissues were quantified ex vivo by LC–MS/MS. Efficacy studies were performed over 2–3 weeks and toxicity assessed by changes in body weight, glucose and white blood cell count. Effects on tumour activity biomarkers were quantified using reverse-phase protein array.

Results

Everolimus administration s.c. in an emulsion decreased the absorption rate but increased the C _max and bio-availability of everolimus compared to standard approaches of administration p.o. or i.p. Everolimus administration s.c. via MP or PLGA-µP reduced the C _max and provided continuous low concentrations of everolimus in the plasma, which inhibited tumour pS6/S6 to a similar degree to oral administration. Toxicities such as changes in body weight or white blood cell count were unaffected. Provided the everolimus concentration was above the free unbound IC50 for proliferation of the tumour cell line, efficacy could be achieved equivalent to that provided by standard oral administration. However, an overall improvement in the TI could not be demonstrated.

Conclusions

Continuous low plasma concentrations of everolimus can provide strong efficacy in preclinical models, which if translatable to the clinic may reduce on-target toxicities and so increase the TI.

http://ift.tt/2vyVr7Z

Advanced Tracheal Adenoid Cystic Carcinoma with Thyroid Invasion Mimicking Thyroid Cancer Treated with Definitive Radiation: Case Report and Review of the Literature

A 54-year-old female patient, a breast cancer survivor and a case of unresectable adenoid cystic carcinoma of the trachea, with thyroid invasion, presented with suprasternal neck swelling mimicking thyroid primary. A literature search was undertaken to highlight this rare presentation. There have been few reports in the literature describing tracheal adenoid cystic carcinoma involving the thyroid.
Case Rep Oncol 2017;10:706–712

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Alternative technique or mitigating strategy for sevoflurane-induced neurodegeneration: a randomized controlled dose-escalation study of dexmedetomidine in neonatal rats

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Abstract

Background. Brain injury in newborn animals from prolonged anaesthetic exposure has raised concerns for millions of children undergoing anaesthesia every yr. Alternative anaesthetic techniques or mitigating strategies are urgently needed to ameliorate potentially harmful effects. We tested dexmedetomidine, both as a single agent alternative technique and as a mitigating adjuvant for sevoflurane anaesthesia.Methods. Neonatal rats were randomized to three injections of dexmedetomidine (5, 25, 50, or 100 µg kg⁻¹ every 2 h), or 6 h of 2.5% sevoflurane as a single agent without or with dexmedetomidine (1, 5, 10, or 20 µg kg⁻¹ every 2 h). Heart rate, oxygen saturation, level of consciousness, and response to pain were assessed. Cell death was quantified in several brain regions.Results. Dexmedetomidine provided lower levels of sedation and pain control than sevoflurane. Exposure to either sevoflurane or dexmedetomidine alone did not cause mortality, but the combination of 2.5% sevoflurane and dexmedetomidine in doses exceeding 1 µg kg⁻¹ did. Sevoflurane increased apoptosis in all brain regions; supplementation with dexmedetomidine exacerbated neuronal injury, potentially as a result of ventilatory or haemodynamic compromise. Dexmedetomidine by itself increased apoptosis only in CA2/3 and the ventral posterior nucleus, but not in prefrontal cortex, retrosplenial cortex, somatosensory cortex, subiculum, lateral dorsal thalamic nucleaus, or hippocampal CA1.Conclusions. We confirm previous findings of sevoflurane-induced neuronal injury. Dexmedetomidine, even in the highest dose, did not cause similar injury, but provided lesser degrees of anaesthesia and pain control. No mitigation of sevoflurane-induced injury was observed with dexmedetomidine supplementation, suggesting that future studies should focus on anaesthetic-sparing effects of dexmedetomidine, rather than injury-preventing effects.

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Clinicopathological features and prognostic validity of WHO grading classification of SI-NENs

Abstract

Background

The clinicopathological characteristics of small intestinal neuroendocrine neoplasms (SI-NENs) and the prognostic validity of WHO grading classification for SI-NENs are still unknown in Asian patients.

Methods

277 patients and 8315 patients with SI-NENs were retrieved respectively from eleven Chinese hospitals and Surveillance, Epidemiology, and End Results (SEER) cancer registry. Overall survival was used as the major study outcome. Survival analysis using Kaplan-Meier analysis with log-rank test and cox regression analysis were applied.

Results

Clinicopathological characteristics of SI-NENs were quite different among different races. Duodenum was the predominant tumor site in Chinese patients and Asian/Pacific Islander patients but not in white patients from SEER database. Patients with duodenal NENs tended to have more localized disease than patients with jejunal/ileal NENs which were confirmed by patients from SEER database. Grade 3 or poorly differentiated/undifferentiated tumor were more common and tumor size was significantly larger in ampullary NENs compared with that in non-ampullary duodenal NENs. As for the prognostic validity of WHO grading classification, survival between patients with grade 1 and grade 2 disease was not significantly different. Ki-67 index of 5% might be a better threshold between grade 1 and grade 2 than Ki-67 index of 2% in SI-NENs.

Conclusions

Our study revealed that the clinicopathological characteristics of SI-NENs among different races were quite different. This might because duodenal NENs was much more common in Chinese patients and Asian/Pacific Islander patients. Duodenal NENs and jejunal/ileal NENs, ampullary and non-ampullary duodenal NENs shared different characteristics. Ki-67 index of 5% might be a better threshold between grade 1 and grade 2 in SI-NENs.

http://ift.tt/2wrG79F

Digital health behaviour change interventions targeting physical activity and diet in cancer survivors: a systematic review and meta-analysis

Abstract

Purpose

The number of cancer survivors has risen substantially due to improvements in early diagnosis and treatment. Health behaviours such as physical activity (PA) and diet can reduce recurrence and mortality, and alleviate negative consequences of cancer and treatments. Digital behaviour change interventions (DBCIs) have the potential to reach large numbers of cancer survivors.

Methods

We conducted a systematic review and meta-analyses of relevant studies identified by a search of Medline, EMBASE, PubMed and CINAHL. Studies which assessed a DBCI with measures of PA, diet and/or sedentary behaviour were included.

Results

Fifteen studies were identified. Random effects meta-analyses showed significant improvements in moderate-vigorous PA (seven studies; mean difference (MD) = 41 min per week; 95% CI 12, 71) and body mass index (BMI)/weight (standardised mean difference (SMD) = −0.23; 95% CI −0.41, −0.05). There was a trend towards significance for reduced fatigue and no significant change in cancer-specific measures of quality of life (QoL). Narrative synthesis revealed mixed evidence for effects on diet, generic QoL measures and self-efficacy and no evidence of an effect on mental health. Two studies suggested improved sleep quality.

Conclusions

DBCIs may improve PA and BMI among cancer survivors, and there is mixed evidence for diet. The number of included studies is small, and risk of bias and heterogeneity was high. Future research should address these limitations with large, high-quality RCTs, with objective measures of PA and sedentary time.

Implications for cancer survivors

Digital technologies offer a promising approach to encourage health behaviour change among cancer survivors.

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A novel CBCT-based method for derivation of CTV-PTV margins for prostate and pelvic lymph nodes treated with stereotactic ablative radiotherapy

Abstract

Background

Methods

Twenty patients with high-risk localized prostate cancer were selected for retrospective review. Individual volumes of interest (prostate, prostate and seminal vesicles and pelvic lymph nodes) were delineated on five representative CBCTs and registered to the planning CT using two registration protocols: bone match or prostate-based soft tissue match. Margins were incrementally expanded around composite CTV structures until 95% overlap was achieved.

Results

CTV-PTV margins of 5.2, 6.5 and 7.6 mm were required for prostate, prostate and seminal vesicles and pelvic lymph nodes respectively using a prostate matching protocol. For the prostate and seminal vesicle structures, margins calculated using our method displayed good agreement with a conventional margin recipe (within ±1.0 mm).

Conclusions

We have presented an alternative method of CTV-PTV margin derivation that is applicable to SABR treatments with more than one isocentric target. These results have informed an institutional trial of prostate and pelvic nodal SABR in men with high-risk localized prostate cancer.

http://ift.tt/2wd2foR

Effect of a 12-week integrative oncology intervention on gastro-intestinal concerns in patients with gynecological and breast cancer undergoing chemotherapy

Abstract

Research on the long-term effects of complementary and integrative medicine (CIM) is limited. In this study, we explore the impact of a CIM intervention on gastro-intestinal (GI)-related concerns in patients with breast/gynecological cancer undergoing chemotherapy. Patients reporting chemotherapy-related GI concerns were referred by their cancer care providers to a CIM consultation and treatments and assessed at baseline and at 12 weeks. The following tools were used: Edmonton Symptom Assessment Scale (ESAS), Measure Yourself Concerns and Wellbeing (MYCAW) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The intervention group was subdivided according to adherence to the integrative care program (AIC), defined as attending ≥4 CIM treatments with ≤30 days between each session. Controls chose not to undergo the CIM consultation or treatments. Of 289 patients reporting GI-related concerns, 42 were treated with CIM and optimally assessed (intervention arm; AIC = 33), as were 32 of controls. ESAS scores for appetite and nausea improved more significantly in the intervention group, more so in the AIC subgroup (appetite, p = 0.025; nausea, p = 0.033). MYCAW scores for GI-related concerns also improved in the intervention group, again more so in the adherent subgroup. EORTC scores improved more significantly with respect to global health (p = 0.021) and cognitive functioning (p = 0.031) in the intervention group, when compared to controls. The integration of a 12-week CIM intervention in conventional supportive cancer care may reduce nausea and improve appetite in patients with breast/gynecological cancer undergoing chemotherapy.

http://ift.tt/2v3kb71

Reproducibility in contouring the neurovascular bundle for prostate cancer radiotherapy

Publication date: Available online 3 August 2017
Source:Practical Radiation Oncology
Author(s): Richard J. Cassidy, Sherif G. Nour, Tian Liu, Jeffrey M. Switchenko, Sibo Tian, Matthew J. Ferris, Robert H. Press, Jim Zhong, Mustafa Abugideiri, Peter J. Rossi, Ashesh B. Jani
PurposeEfforts to define the neurovascular bundle (NVB) for prostate radiation have varied. In this series, we sought to determine the reproducibility and reliability of contouring the classical posterolateral NVB on dedicated pelvic magnetic-resonance imaging (MRI).MethodsOne hundred and twenty total NVB structures were defined on ten 3-Tesla pelvic MRI's in patients with prostate cancer but without extraprostatic extension. One pelvic radiologist served as the expert in contouring the right and left NVB for each case. Five radiation oncologists, with varying levels of experience, contoured the right and left NVB on these same cases. The intraclass correlation coefficient (ICC) across each rater and the expert, Pearson's correlation coefficient (PCC) between each rater and the expert, and the Dice similarity coefficient (DSC) between each rater and the expert were calculated to evaluate contour agreement and overlap.ResultsThe overall ICC was 0.89 (95% CI: 0.81–0.95). The PCC for: rater 1 was 0.95 (95% CI: 0.86–0.98), rater 2 was 0.98 (95% CI: 0.95–0.99), rater 3 was 0.94 (95% CI: 0.86–0.98), rater 4 was 0.98 (95% CI: 0.95–0.99), and rater 5 was 0.84 (95% CI: 0.63–0.93). The mean DSC for: rater 1 was 0.72 (standard deviation: 0.07), rater 2 was 0.72 (standard deviation: 0.06), rater 3 was 0.73 (standard deviation: 0.09), rater 4 was 0.74 (standard deviation: 0.09), and rater 5 was 0.68 (standard deviation: 0.13). Overall, across all raters, the average DSC was 0.72 (standard deviation: 0.09).ConclusionsThe classic posterolateral NVB can be accurately and reliably be contoured on 3-T pelvic MRI's by radiation oncologists.

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The effect of lipiodol deposition in HCC after TACE on the necrosis range of PMCT

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IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

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Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma

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Outcomes of adding induction chemotherapy to concurrent chemoradiotherapy for stage T3N0-1 nasopharyngeal carcinoma: a propensity-matched study

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A modified Edmonton Symptom Assessment Scale for symptom clusters in radiation oncology patients

Abstract

Patient-reported outcomes regarding symptom burden may provide valuable information in addition to physician assessment. Systematic collection of patient-reported outcomes may be an important metric to identify unmet needs and improve quality of patient care. To understand common symptoms of patients seen in radiation oncology clinic, we examined the prospectively collected modified Edmonton Symptom Assessment Scale (ESAS-r) data to explore symptom clusters. Our clinic established use of a modified Edmonton Symptom Assessment Scale in August 2015. All outpatients presenting for radiation oncology services completed the form at each clinic visit. Symptom clusters are defined by two or more symptoms that are interrelated and occur simultaneously with a high degree of predictability. A sample of 916 de-identified surveys was assessed statistically using principal component analysis (PCA) with varimax rotation to determine independent clustering between the symptoms queried. We found four major clusters of symptoms: Tiredness (tired, drowsiness; PC1), Loss of Appetite (nausea, lack of appetite; PC2), Low Well-Being (overall & spiritual well-being; PC3), and Depression (depression, anxiety; PC4). These accounted for 46%, 9.2%, 7.6%, and 7% of total variance, respectively. Internal consistency using Cronbach's alpha was 0.87, 0.7, 0.82, and 0.87, respectively. The most frequent write-in item was itchiness, present in 24% of the 148 patients responding. Assessment of patients seen in a large radiation oncology clinic revealed several symptom clusters. {Tiredness and drowsiness} represents a major symptom cluster. Itchiness may be underrecognized.

This manuscript demonstrates the importance of collecting patient-reported symptoms to optimize clinical care in a large radiation oncology department. Using a modified Edmonton Symptom Assessment Scale to collect patient-reported symptoms at each clinic encounter, our investigation was able to demonstrated that several symptom clusters were noted, with {tiredness and drowsiness} being a major symptom cluster in this patient population.

http://ift.tt/2wdOS8e

Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients

Abstract

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age-related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age-related risks for the five major VHL-associated tumors were evaluated using Kaplan–Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age-adjusted telomere length ≤ 0.44) suffered higher age-related risks for VHL-associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age-related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL-associated tumors.

We evaluated the relationship between blood telomere length and age-related risk of the five major tumors in VHL patients in the largest Chinese VHL cohort. Patients with shorter telomere length(age-adjusted telomere length ≤ 0.44) suffered higher age-related risks for VHL-associated central nervous system hemangioblastomas, renal cell carcinoma and pancreatic cyst and neuroendocrine tumors.

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Racial disparities in the utilization of preventive health services among older women with early-stage endometrial cancer enrolled in Medicare

Abstract

To assess differences in the receipt of preventive health services by race/ethnicity among older women with endometrial cancer enrolled in Medicare, we conducted a retrospective population-based cohort study of women diagnosed with endometrial cancer from 2001 to 2011 in the Surveillance Epidemiology and End Results (SEER)-Medicare database. Women with stage I or II endometrial cancer of epithelial origin were included. The exposure was race/ethnicity (Non-Hispanic [NH] White, NH Black, Hispanic, and NH Asian/Pacific Islander [PI]). The services examined were receipt of influenza vaccination and screening tests for diabetes mellitus, hyperlipidemia, and breast cancer. We used multivariate logistic regression to estimate odds ratios with 95% confidence intervals (CI) adjusted for age, region, and year of diagnosis. A total of 13,054 women were included. In the 2 years after diagnosis, receipt of any influenza vaccine ranged from 45% among NH Black women to 67% among NH White women; receipt of a mammogram ranged from 65% among NH Black women to 74% among NH White women. Relative to NH White women, NH Black women had a lower likelihood of receiving both influenza vaccination (adjusted odds ratio [aOR] 0.40, 95% CI 0.33–0.44) and screening mammography (aOR 0.64, 95% CI 0.52–0.79). Hispanic women also were less likely to receive influenza vaccination than NH White women (aOR 0.61, 95% CI 0.51–0.72). There were no significant differences across racial groups for diabetes or cholesterol screening services. Among older women with early-stage endometrial cancer, racial disparities exist in the utilization of some preventive services.

Women with early-stage endometrial cancer are more likely to die from medical comorbidities than cancer. Endometrial cancer survivors have low utilization of preventive health services, and in particular racial disparities exist for breast cancer and diabetes mellitus screening, as well as influenza vaccination.

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First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases

Abstract

Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic radiosurgery (SRS) for brain metastases (BM). Expected outcomes following SRS for BM include tumor control/shrinkage, local progression and radiation necrosis. 1427 patients with 4283 BM lesions were treated using SRS at Cleveland Clinic from 2000 to 2012. Clinical, imaging and radiosurgery data were collected from the database. Local tumor progression and RN were the primary end points and correlated with patient and tumor-related variables. 5.7% of lesions developed radiographic RN and 3.6% showed local progression at 6 months. Absence of new extracranial metastasis (P < 0.001), response to SRS at first follow-up scan (local progression versus stable size (P < 0.001), partial resolution versus complete resolution at first follow up [P = 0.009]), prior SRS to the same lesion (P < 0.001), IDL% (≤55; P < 0.001), maximum tumor diameter (>0.9 cm; P < 0.001) and MD/PD gradient index (≤1.8, P < 0.001) were independent predictors of high risk of local tumor progression. Absence of systemic metastases (P = 0.029), good neurological function at 1st follow-up (P ≤ 0.001), no prior SRS to other lesion (P = 0.024), low conformity index (≤1.9) (P = 0.009), large maximum target diameter (>0.9 cm) (P = 0.003) and response to SRS (tumor progression vs. stable size following SRS [P < 0.001]) were independent predictors of high risk of radiographic RN. Complete tumor response at first follow-up, maximum tumor diameter <0.9 cm, tumor volume <2.4 cc and no prior SRS to the index lesion are good prognostic factors with reduced risk of LP following SRS. Complete tumor response to SRS, poor neurological function at first follow-up, prior SRS to other lesions and high conformity index are favorable factors for not developing RN. Stable or partial response at first follow-up after SRS have same impact on local progression and RN compared to those with complete resolution or progression.

Our study provides the role of first follow-up radiographic response after SRS in predicting long-term tumor response and radiation necrosis.

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Antineoplastic effects of histone deacetylase inhibitors in neuroendocrine cancer cells are mediated through transcriptional regulation of Notch1 by activator protein 1

Abstract

Notch signaling is minimally active in neuroendocrine (NE) cancer cells. While histone deacetylase inhibitors (HDACi) suppress NE cancer growth by inducing Notch, the molecular mechanism underlying this interplay has not yet been defined. NE cancer cell lines BON, H727, and MZ-CRC-1 were treated with known HDACi Thailadepsin-A (TDP-A) and valproic acid (VPA), and Notch1 mRNA expression was measured with RT-PCR. Truncated genomic fragments of the Notch1 promotor region fused with luciferase reporter were used to identify the potential transcription factor (TF) binding site. The key regulatory TF was identified with the electrophoretic mobility shift assay (EMSA). The effect of HDACi on Notch1 level was determined before and after silencing the TF. TDP-A and VPA induced Notch1 mRNA in a dose-dependent manner. A functional DNA motif at −80 to −52 from the Notch1 start codon responsible for the HDACi-dependent Notch1 induction was identified. Mutation of this core sequence failed to induce luciferase activity despite HDACi treatment. EMSA showed the greatest gel shift with AP-1 in nuclear extracts. Knockdown of AP-1 significantly attenuated the effect of HDACi on Notch1 induction. Interestingly, AP-1 transfection did not alter Notch1 level, suggesting that AP-1 is necessary but insufficient for HDACi activation of Notch1. Therefore, AP-1 is the TF that binds to a specific transcription-binding site within the Notch1 promotor region to trigger Notch1 transcription. Elucidating the HDACi activation mechanism may lead to the development of novel therapeutic options against NE cancers and facilitate the identification of clinical responders and prevent adverse effects.

While we know that molecules that inhibit histone deacetylase transform the malignant phenotype and suppress neuroendocrine cancer growth by inducing Notch isoforms, the molecular mechanism underlying this interplay has not yet been determined. We report here that AP-1 binds to the Notch1 active promoter site and is necessary for Notch1 induction in neuroendocrine cancers.

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Adhesive arachnoiditis in mixed connective tissue disease: a rare neurological manifestation

Maria Usman Khan Dec 16, 2016; 2016:bcr2016217418-bcr2016217418 case-report

http://ift.tt/2u7jXsM

Effects of hepatic ischemia-reperfusion injury on the blood-brain barrier permeability to [ 14 C] and [ 13 C]sucrose

Abstract

Hepatic encephalopathy that is associated with severe liver failure may compromise the blood-brain barrier (BBB) integrity. However, the effects of less severe liver diseases, in the absence of overt encephalopathy, on the BBB are not well understood. The goal of the current study was to investigate the effects of hepatic ischemia-reperfusion (IR) injury on the BBB tight junction permeability to small, hydrophilic molecules using the widely used [¹⁴C]sucrose and recently-proposed alternative [¹³C]sucrose as markers. Rats were subjected to 20 min of hepatic ischemia or sham surgery, followed by 8 h of reperfusion before administration of a single bolus dose of [¹⁴C] or [¹³C]sucrose and collection of serial (0–30 min) blood and plasma and terminal brain samples. The concentrations of [¹⁴C] and [¹³C]sucrose in the samples were determined by measurement of total radioactivity (nonspecific) and LC-MS/MS (specific), respectively. IR injury significantly increased the blood, plasma, and brain concentrations of both [¹⁴C] and [¹³C]sucrose. However, when the brain concentrations were corrected for their respective area under the blood concentration-time curve, only [¹⁴C]sucrose showed significantly higher (30%) BBB permeability values in the IR animals. Because [¹³C]sucrose is a more specific BBB permeability marker, these data indicate that our animal model of hepatic IR injury does not affect the BBB tight junction permeability to small, hydrophilic molecules. Methodological differences among studies of the effects of liver diseases on the BBB permeability may confound the conclusions of such studies.

http://ift.tt/2v2Z3Oa

Solitary Skeletal Muscle Metastasis as First Site of Recurrence of Cervical Cancer: A Case Report

Cervical cancer is the fourth most common cancer in women worldwide, with a large majority of prevalence (85%) in developing countries. As of 2012, it accounts for 7.5% of all female cancer deaths. Despite its high prevalence, skeletal muscle metastasis from cervical cancer is extremely uncommon. In our extensive literature search, we were able to find only 8 cases where skeletal muscle metastasis was the only site of recurrence. We report a case of a 52-year-old African-American woman with a past medical history of cervical cancer (stage IIIB) who presented with pain and swelling in her left upper arm over the preceding 2 months. MRI of the left upper arm showed a solid well-circumscribed mass measuring 7.0 × 2.8 × 2.5 cm, deep to the biceps. Biopsy of the mass revealed a metastatic squamous cell carcinoma that was p16-positive. PET scan showed that the lesion was the sole site of metastasis. She received local radiation with concurrent chemotherapy. Follow-up MRI 6 months after the completion of therapy showed resolution of the mass. She has remained disease-free for the last 24 months as evidenced by a PET/CT scan in May 2016. In this case report, we discuss the role of imaging and pathology in the diagnosis of a solitary metastatic lesion. This case also emphasizes the importance of a close follow-up which aids in early intervention, increasing overall survival.
Case Rep Oncol 2017;10:694–698

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Correlation between Tumor-Infiltrating Lymphocytes and Pathological Response in Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy in H. Adam Malik General Hospital

Background: Tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value, particularly in triple-negative and human epidermal growth factor receptor-2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy, and there is a strong correlation with pathologically complete response. In this study, we analyzed whether changes in TILs take place after neoadjuvant therapy and if they correlate with pathological response to treatment. Patients and Methods: We retrospectively analyzed the specimen slides from the Department of Anatomic Pathology of H. Adam Malik General Hospital during 2011–2015. We identified 51 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. Each case was also defined as high- or low-TIL breast cancer adopting previously validated cutoffs. Results: The mean age of the 51 patients was 49.22 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 49 (96%) patients, and there were 2 (4%) patients with lobular carcinoma. The histopathological grading for high TILs was grade 1 in 5 patients, grade 2 in 15 patients, and grade 3 in 3 patients. High TILs that had a pathologically complete response were found in 47.8% of patients, and low TILs were found in 28.8%. There was no significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.157). Conclusions: This research has not been able to demonstrate a significant correlation between TILs and pathological response in patients with locally advanced breast cancer who received neoadjuvant chemotherapy, but high TILs were more likely to have a complete response. Further information may prove useful for future biomarker trials.
Case Rep Oncol 2017;10:699–705

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Ischemic Colitis Associated with Paclitaxel and Carboplatin Combination

A 62-year-old white female with a history of early-stage triple-negative breast cancer on a combination of carboplatin and paclitaxel in the adjuvant setting presented with lower gastrointestinal bleeding. She tolerated 4 cycles of dose-dense adriamycin/cyclophosphamide with no major symptoms. After 6 cycles of weekly paclitaxel in combination with carboplatin every 3 weeks, she presented with diarrhea and lower gastrointestinal bleeding. Colonosopic examination showed erythema and inflammation in the splenic flexure, descending colon, and sigmoid colon consistent with ischemic colitis. Pathology favored the same diagnosis. She was treated conservatively with intravenous fluids and bowel rest. Chemotherapy was held for 2 weeks and resumed after recovery without carboplatin. She was able to tolerate the remaining 6 cycles of paclitaxel with no recurrence of her symptoms.
Case Rep Oncol 2017;10:689–693

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Interstitial Lung Disease Following Single-Agent Nanoparticle Albumin-Bound Paclitaxel Treatment in Patients with Advanced Non-Small Cell Lung Cancer

Interstitial lung disease (ILD) is a serious and potentially fatal adverse event in lung cancer therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel, solvent-free formulation of paclitaxel (PTX). Although the incidence of nab-PTX-induced ILD is not clear, it is generally considered that this formulation presents a similar risk of developing ILD as PTX. Here, we report 3 patients who developed severe ILD following treatment with nab-PTX. We draw attention to the risk of developing drug-induced ILD following nab-PTX treatment, and highlight that this novel formulation might therefore not be as safe as PTX with respect to the development of ILD.
Case Rep Oncol 2017;10:683–688

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Successful weaning from mechanical ventilation in a patient with surfactant protein C deficiency presenting with severe neonatal respiratory distress

Jeroen van Hoorn Mar 19, 2014; 2014:bcr2013203053-bcr2013203053 case-report

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Two cases of rare benign mucosal lesions of the stomach

Komal Agrawal Jul 31, 2013; 2013:bcr2013009506-bcr2013009506 case-report

http://ift.tt/2fed7Pu

Progressive multifocal leukoencephalopathy in a patient with Good's syndrome

Olafur Sveinsson Jul 29, 2013; 2013:bcr2013009763-bcr2013009763 case-report

http://ift.tt/2htozaz

The McKittrick-Wheelock syndrome: a rare cause of chronic diarrhoea

Jana G Hashash Apr 15, 2013; 2013:bcr2013009208-bcr2013009208 case-report

http://ift.tt/2feLxl3

Prematurity, macrosomia, hyperinsulinaemic hypoglycaemia and a dominant ABCC8 gene mutation

Dana Khoriati Apr 5, 2013; 2013:bcr2013008767-bcr2013008767 case-report

http://ift.tt/2htosvF

Nasopalatine canal cyst: often missed

Saurabh Srivastava Mar 27, 2013; 2013:bcr2012007548-bcr2012007548 case-report

http://ift.tt/2fdZvDN

Mediastinal leiomyosarcoma concurrent with intra-aortic thrombosis

Masayoshi Yoshida Feb 20, 2013; 2013:bcr2012007527-bcr2012007527 case-report

http://ift.tt/2htvqAR

Pulmonary hypertension in a patient with hereditary haemorrhagic telangiectasia

Davinder Chadha Feb 1, 2013; 2013:bcr2012008352-bcr2012008352 case-report

http://ift.tt/2fecSny

Using a bradykinin blocker in ACE inhibitor-associated angioedema in the emergency department

Andrew Volans Jan 31, 2013; 2013:bcr2012008295-bcr2012008295 case-report

http://ift.tt/2htoe7N

Prosthetic valve endocarditis caused by Propionibacterium species successfully treated with coadministered rifampin: report of two cases

Dominique Laurent Braun Jan 25, 2013; 2013:bcr2012007204-bcr2012007204 case-report

http://ift.tt/2fecMwc

Necrotising fasciitis caused by P aeruginosa in a male patient with chronic lymphocytic leukaemia

Christopher Emmett Jan 23, 2013; 2013:bcr2012008133-bcr2012008133 case-report

http://ift.tt/2ht2HMu

Three cases of severely disseminated Staphylococcus aureus infection in patients treated with tocilizumab

Mai TT Nguyen Jan 2, 2013; 2013:bcr2012007413-bcr2012007413 case-report

http://ift.tt/2feDEfw

Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury

Amanda Nicoll Nov 6, 2012; 2012:bcr2012006543-bcr2012006543 case-report

http://ift.tt/2huoV0w

Fetal warfarin syndrome

Luke D Starling Nov 1, 2012; 2012:bcr2012007344-bcr2012007344 case-report

http://ift.tt/2feDuEW

Bilateral hypogeusia caused by a small lesion in the lower midbrain tegmentum

Takao Hashimoto Sep 11, 2012; 2012:bcr2012006837-bcr2012006837 case-report

http://ift.tt/2ht1kh0

A qualitative investigation among men who have sex with men on the acceptability of performing a self- or partner anal exam to screen for anal cancer

Abstract

Purpose

Persistent infection with oncogenic human papillomavirus (HPV) is the primary cause of anal cancer, a disease that disproportionately affects men who have sex with men (MSM); however, there is no uniform screening protocol to detect anal cancer. This qualitative study explores whether a self-anal exam (SAE) or partner anal exam (PAE), that includes self-palpation or palpation of a partner's anal canal, is an acceptable and self-efficacious screening test, which will cue appropriate follow-up care in MSM.

Methods

Twenty-four MSM living in Houston took part in four focus group sessions eliciting their responses to a study teaching them to perform an SAE or PAE (SAE/PAE). Participants were asked about the acceptability and feasibility of executing an SAE/PAE routinely. Thematic analysis of session transcripts was used to identify common patterns in participant responses. Results: Overall, participants expressed self-efficacy for performing an SAE/PAE and voiced a preference for being taught the procedure by a clinician. Participants agreed that they would consult with a clinician if they ever discovered an abnormality while performing an SAE/PAE. A lack of knowledge about anal cancer among MSM may present a barrier to adopting SAE/PAE. In discussing their experience of the exams, some participants suggested that it could become a routine practice for them.

Conclusions

Our findings suggest that SAE and PAE, as a screen for anal cancer, are acceptable and feasible to MSM. Future research should explore attitudes and beliefs of MSM, with the aim of improving anal cancer education and understanding of pathologic findings.

http://ift.tt/2uqncuB

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months

Abstract

Background

Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial.

Methods

Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1–3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95–100%), gross total resection (90–95%), incomplete resection (50–90%), and biopsy (<50%) and correlated with local control rate and outcome. Patients were stratified according to the International Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test.

Results

A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS.

Conclusions

In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of complications.

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Assessing the Effectiveness of a Knowledge-Based Intervention to Tackle Barriers to Cervical Screening: A Pilot Study

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Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies

Abstract

Background: Relapsed/metastatic salivary gland carcinomas (SGC) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease.Patients and Methods: From a series of 85,686 clinical cases, DNA was extracted from 40 µm of FFPE sections for 623 consecutive SGC. CGP was performed on hybridization-captured, adaptor ligation-based libraries (mean coverage depth >500X) for up to 315 cancer-related genes. Tumor mutational burden (TMB) was determined on 1.1 Mb of sequenced DNA. All classes of alterations, base substitutions, short insertions/deletions, copy number changes and rearrangements/fusions were determined simultaneously.Results: The clinically more indolent SGC including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), polymorphous low grade adenocarcinoma (PLGA), mammary analogue secretory carcinoma (MASC), and epithelial-myoepithelial carcinomas have significantly fewer genomic alterations (GA), TP53 mutations, and lower TMB than the typically more aggressive SGCs including mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), adenocarcinoma, not otherwise specified (AD-NOS), carcinoma NOS (CA-NOS) and carcinoma ex pleomorphic adenoma (Ca ex PA). The more aggressive SGCs are commonly driven by ERBB2 PI3K pathway GAs. Additional targetable GAs are frequently seen.Conclusions: Genomic profiling of SGCs demonstrates important differences between traditionally indolent and aggressive cancers. These differences may provide therapeutic options in the future.

http://ift.tt/2wdkxGT