An Automated Multiparametric MRI Quantitative Imaging Prostate Habitat Risk Scoring System for Defining External Beam Radiotherapy Boost Volumes

Publication date: Available online 13 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Radka Stoyanova, Felix Chinea, Deukwoo Kwon, Isildinha M. Reis, Yohann Tschudi, Nestor A. Parra, Adrian L. Breto, Kyle R. Padgett, Alan Dal Pra, Matthew C. Abramowitz, Oleksandr N. Kryvenko, Sanoj Punnen, Alan Pollack
PurposeTo develop a prostate tumor habitat risk scoring (HRS) system based on multiparametric MRI (mpMRI) referenced to prostatectomy Gleason Score (GS) for automatic delineation of Gross Tumor Volumes (GTVs). A workflow for integration of HRS into radiotherapy (RT) boost volume dose escalation was developed in the framework of a Phase II randomized clinical trial (BLaStM).Materials and MethodsAn automated quantitative mpMRI based 10 point pixel by pixel method was optimized to prostatectomy GSs and volumes using referenced Dynamic Contrast Enhanced and Apparent Diffusion Coefficient sequences. The HRS contours were migrated to the planning CT for boost volume generation.ResultsThere were 51 regions of interest (ROIs) in 12 patients who underwent radical prostatectomy (RP) (26 with GS≥7 and 25 with GS6). The resultant heat maps showed inter- and intra-tumoral heterogeneity. The HRS6 level was significantly associated with RP ROIs (slope 1.09, r=0.767; p<.0001). For predicting the likelihood of cancer, GS≥7 and GS≥8, HRS6 AUCs were 0.718, 0.802 and 0.897, respectively. HRS was superior to the Prostate Imaging, Reporting and Diagnosis System 4/5 classification, wherein the AUCs were 0.62, 0.64 and 0.617, respectively (difference with HR6, p<.0001). HRS maps were created for the first 37 assessable patients on the BLaStM trial. There were an average of 1.38 habitat boost volumes per patient at a total boost volume average of 3.6 cc.ConclusionsAn automated quantitative mpMRI based method was developed to objectively guide dose escalation to high risk habitat volumes based on prostatectomy GS.

Teaser

Prostate multiparamateric MRI has a high sensitivity and specificity for identifying tumor regions in the prostate; but, there is subjectivity in defining high risk 3D volumes that could be boosted, as opposed to entire prostate dose escalation. Registering to prostatectomy Gleason score, a habitat risk score based on pixel by pixel quantitative diffusion and perfusion was developed and then applied to guiding radiotherapy boost volumes in the background of a randomized Phase II clinical trial.


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Fever of unknown origin: a rare presentation of giant hepatic hemangioma

Abstract

Hepatic hemangioma is mostly asymptomatic and incidental finding on imaging. Fever of unknown origin as a sole presentation is rare. We present an interesting case report of a 49-year-old female, who presented with fever for three months. Extensive blood investigations and infectious workup failed to reveal the cause. Contrast computed tomography of abdomen revealed a giant (15 × 11 cm) hemangioma arising from left lateral segment of liver, and was attributed as a cause for fever. Surgical excision of hemangioma completely ameliorated the fever.

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Nodular macroregenerative tissue as a pattern of regeneration in cholangiopathic disorders

Abstract

Background

Published case series have described central hepatic macroregenerative nodules or masses as a common feature of Alagille syndrome. Our experience suggests this regenerative pattern can be seen more generally in cholangiopathic disorders.

Objective

To define the frequency of central regenerative tissue in Alagille syndrome and other cholangiopathic disorders and to describe the typical appearance of such regenerative tissue.

Materials and methods

We conducted a retrospective study of CT and MR imaging performed in children and young adults with cholangiopathic disorders between January 2000 and June 2016. Two pediatric radiologists reviewed images in consensus for the presence and features of macroregenerative tissue. Tissue histopathology, when available, was retrieved from the medical record.

Results

Of 226 patients with cholangiopathic disorders, 23% (52/226) had macroregenerative tissue, and this tissue was central in 96% (50/52). Tissue was well defined and mass-like in 38% (20/52). Regenerative tissue was most common among the subset of patients with Langerhans cell histiocytosis with hepatic involvement (71%, 5/7) and was identified in 43% (16/37) of patients with Alagille syndrome. Regenerative tissue was iso- to hyperintense on T1-weighted MR sequences in 96% (50/52) of cases and hypointense on T2-weighted MR imaging in 94% (48/51). Arterial phase hyperenhancement was present in only five patients (12% of 43), none of whom showed portal venous phase washout. Histopathology was available for 20 cases, all showing benign regenerative tissue.

Conclusion

Central mass-like regeneration appears to be a common regenerative pattern in cholangiopathic disorders and should not be mistaken for malignancy.

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Comparison of ultrasound versus computed tomography for the detection of kidney stones in the pediatric population: a clinical effectiveness study

Abstract

Background

The incidence of pediatric nephrolithiasis in the United States is increasing. There is a paucity of literature comparing the diagnostic performance of computed ultrasound (US) to tomography (CT) in the pediatric population.

Objective

To determine the diagnostic performance of renal US for nephrolithiasis in children using a clinical effectiveness approach.

Materials and methods

Institutional review board approval with a waiver of informed consent was obtained for this retrospective, HIPAA-complaint investigation. Billing records and imaging reports were used to identify children (≤18 years old) evaluated for nephrolithiasis by both US and unenhanced CT within 24 h between March 2012 and March 2017. Imaging reports were reviewed for presence, number, size and location of kidney stones. Diagnostic performance of US (reference standard=CT) was calculated per renal unit (left/right kidney) and per renal sector (four sectors per kidney). For sector analysis, US was considered truly positive if a stone was identified at CT in the same or an adjacent sector.

Results

There were 68 renal stones identified by CT in 30/69 patients (43%). Mean patient age was 14.7±3.6 years, and 35 were boys. For detecting nephrolithiasis in any kidney, US was 66.7% (48.8–80.8%) sensitive and 97.4% (86.8–99.9%) specific (positive predictive value=95.2% [77.3–99.8%], negative predictive value=79.2% [65.7–88.3%], positive likelihood ratio=26.0). Per renal sector, US was 59.7% (46.7–71.4%) sensitive and 97.4% (95.5–98.5%) specific (positive predictive value=72.3% [58.2–83.1%], negative predictive value=95.4% [93.2–96.9%], positive likelihood ratio=22.5). Of the 30 stones not detected by US, only 3 were >3 mm at CT.

Conclusion

In clinical practice, US has high specificity for detecting nephrolithiasis in children but only moderate sensitivity and false negatives are common.

https://ift.tt/2JzdDFW

Hermes

https://ift.tt/2HMZcIA

Pediatric Radiology Continuing Medical Education Activity

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Reversible lesions of the corpus callosum with initially restricted diffusion in a series of Caucasian children

Abstract

Background

Reversible lesions of the corpus callosum with initial restricted diffusion on diffusion-weighted imaging (DWI) are rare and mainly described in the south Asiatic population.

Objective

The purpose of this study was to describe the clinical presentation, imaging findings, prognosis and etiology of transient restricted diffusion lesions of the corpus callosum in a series of Caucasian children.

Materials and methods

Seven children presenting with a transient restricted DWI lesion of the corpus callosum were included. Their clinical presentations and paraclinical examinations were investigated in addition to their MRI findings during the acute phase and at follow-up.

Results

Five patients initially presenting with prodromal flu-like symptoms were diagnosed with mild encephalopathy with reversible corpus callosum lesions, three of which were due to the influenza virus. For two patients (twins) with a stroke-like presentation and without febrile illness, a central nervous system manifestation of X-linked Charcot-Marie-Tooth disease with connexin 32 mutation was diagnosed. All patients had a good clinical prognosis without clinical sequelae or residual MRI lesion for all patients at follow-up.

Conclusion

A transient lesion of the corpus callosum with restricted diffusion should prompt the radiologist to suggest an infectious trigger in children. The prognosis of these patients was good with normalization of clinical symptoms and MRI without any specific treatment.

https://ift.tt/2LMF7og

The European Society of Paediatric Radiology launches European Diploma in Paediatric Radiology

Abstract

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https://ift.tt/2sVATDX

Reversible lesions of the splenium of the corpus callosum in children — additional evidence from a Caucasian population

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Increased risk of symptomatic upper-extremity venous thrombosis with multiple peripherally inserted central catheter insertions in pediatric patients

Abstract

Background

Peripherally inserted central catheters (PICCs) are associated with superficial and deep venous thrombosis of the arm.

Objective

The purpose of this study was to analyze the sequelae of repeated upper limb PICC insertions in children, in terms of the frequency of upper limb thrombosis in this patient group.

Materials and methods

The study population included all children who underwent their first successful arm PICC insertion between January 2010 and December 2015. We included subsequent ipsilateral arm PICCs in the analysis. Patients were followed until March 2016 or until any alternative central venous line insertion. For each PICC insertion, we collected demographic variables and line characteristics. We correlated all symptomatic deep and superficial thromboses of the arm with the PICC database.

Results

Applying inclusion and exclusion criteria, 2,180 PICCs remained for analysis. We identified first, second, third and fourth PICC insertions in the same arm in 1,955, 181, 38 and 6 patients, respectively. In total there were 57 upper body deep symptomatic thrombotic events. An increasing odds ratio was seen with higher numbers of PICC insertions, which was significant when comparing the first with the third and fourth PICC insertions in the same arm (odds ratio [OR] 6.00, 95% confidence interval [CI] 2.25–16.04, P=0.0004). Double-lumen PICCs were associated with a significantly higher risk of thrombosis than single lumen (OR 2.77, 95% CI 1.72-4.47, P=0.0003).

Conclusion

Repetitive PICC insertions in the same arm are associated with an increased risk of symptomatic thrombosis. Double-lumen PICCs are associated with a higher risk of thrombosis compared to single-lumen lines.

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Age-related apparent diffusion coefficients of lumbar vertebrae in healthy children at 1.5 T

Abstract

Background

Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) calculation is important for detecting bone marrow pathologies.

Objective

To investigate age-related differences of lumbar vertebral body ADC to establish normal values for healthy children.

Materials and methods

Forty-nine healthy children without any history of oncological or hematological diseases (10.2±4.7 years, range: 0–20 years) were included in this retrospective study. All magnetic resonance imaging (MRI) examinations were performed at 1.5 T and with similar scan parameters. The diffusion-weighted sequences were performed with b values of 50, 400 and 800 s/mm². ADC values were measured by placing regions of interest at three different levels within each lumbar vertebral body (L1 to L5). ADC values were analyzed for different age groups (0–2 years, 3–6 years, 7–11 years, 12–14 years, 15–20 years), for each vertebral and intravertebral level.

Results

The mean ADC of the whole study group was 0.60±0.09 × 10⁻³ mm²/s. Children between the ages of 12 and 14 years had significantly higher ADC compared to the other age groups (P≤0.0003). ADC values were significantly higher in the 1st lumbar vertebral body compared to the other levels of the lumbar spine (P<0.005) with the exception of L5, and in the upper third of the vertebral bodies compared to the middle or lower thirds (P≤0.003).

Conclusion

The age-, vertebral- and intravertebral level-dependent differences in ADC suggest a varying composition and cellularity in different age groups and in different locations.

https://ift.tt/2LMF3ow

Survivorship Care Plan Implementation in US Cancer Programs: a National Survey of Cancer Care Providers

Abstract

Survivorship care plans (SCPs)—documents intended to improve care for cancer survivors who have completed active treatment—are required, yet implementation is poor. We sought to understand SCP implementation in cancer programs in the USA with the objective of identifying opportunities for improvement. We recruited cancer care providers in the USA via several cancer care networks to participate in a survey regarding SCP implementation. We used descriptive statistics to analyze the data. Three hundred ninety-five providers from diverse cancer programs in 47 states and Washington, DC responded to the survey. The timing of SCP implementation varied across and within cancer programs, with approximately 40% of respondents reporting developing SCPs more than 3 months after primary treatment or adjuvant therapy completion. Nurse navigators were responsible for 48–58% of each stage of SCP implementation. Processes that could have been automated often occurred in-person or via phone and vice versa. Respondents reported spending more than 2 h per SCP to complete all stages of implementation, of which less than a third was reimbursed by third-party payers. We identified several opportunities for improving SCP implementation, including broadening the base of responsibility, optimizing modes of communication, decreasing the time required and increasing the funding available, and limiting variation in SCP implementation across and within cancer programs. Future work should assess the influence of approaches to SCP implementation on desired outcomes.

https://ift.tt/2l6tRHW

Borderline resectable pancreatic cancer. challenges and controversies

Publication date: Available online 13 June 2018
Source:Cancer Treatment Reviews
Author(s): Luis Sabater, Elena Muñoz, Susana Roselló, Dimitri Dorcaratto, Marina Garcés-Albir, Marisol Huerta, Desamparados Roda, María Carmen Gómez-Mateo, Antonio Ferrández-Izquierdo, Antonio Darder, Andrés Cervantes
Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by sugery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic cancer, the complexity of its management and controversies and point out where further research and international cooperation for a consensus strategy is urgently needed.



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Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways

Abstract

Background

Despite recent advances in diagnosis and treatment, prostate cancer (PCa) remains the leading cause of cancer-related deaths in men. Current treatments offered in the clinics are often toxic and have severe side effects. Hence, to treat and manage PCa, new agents with fewer side effects or having potential to reduce side effects of conventional therapy are needed. In this study, we show anti-cancer effects of quercetin, an abundant bioflavonoid commonly used to treat prostatitis, and defined quercetin-induced cellular and molecular changes leading to PCa cell death.

Methods

Cell viability was assessed using MTT. Cell death mode, mitochondrial outer membrane potential, and oxidative stress levels were determined by flow cytometry using Annexin V-7 AAD dual staining kit, JC-1 dye, and ROS detection kit, respectively. Antibody microarray and western blot were used to delineate the molecular changes induced by quercetin.

Results

PCa cells treated with various concentrations of quercetin showed time- and dose-dependent decrease in cell viability compared to controls, without affecting normal prostate epithelial cells. Quercetin led to apoptotic and necrotic cell death in PCa cells by affecting the mitochondrial integrity and disturbing the ROS homeostasis depending upon the genetic makeup and oxidative status of the cells. LNCaP and PC-3 cells that have an oxidative cellular environment showed ROS quenching after quercetin treatment while DU-145 showed rise in ROS levels despite having a highly reductive environment. Opposing effects of quercetin were also observed on the pro-survival pathways of PCa cells. PCa cells with mutated p53 (DU-145) and increased ROS showed significant reduction in the activation of pro-survival Akt pathway while Raf/MEK were activated in response to quercetin. PC-3 cells lacking p53 and PTEN with reduced ROS levels showed significant activation of Akt and NF-κB pathway. Although some of these changes are commonly associated with oncogenic response, the cumulative effect of these alterations is PCa cell death.

Conclusions

Our results demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways. Quercetin could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.

https://ift.tt/2JIzwi2

Nuclear PTEN localization contributes to DNA damage repair in Endometrial cancer and could have a diagnostic benefit for therapeutic management of the disease.

Endometrial adenocarcinoma (EndoCA) is the most common gynecological cancer type in the US, and its incidence is increasing. The majority of patients are disease-free after surgical resection of stage I tumors, which is often followed by radiation therapy, but most patients with advanced disease recur and have a poor prognosis, largely because the tumors become refractory to cytotoxic chemotherapies. PTEN, a commonly mutated tumor suppressor in EndoCAs, is well known for its ability to inhibit the AKT/mTOR signaling pathway. Nuclear functions for PTEN have been proposed as well, but whether those affect EndoCA development, progression, or outcomes is not well understood. Using immunohistochemistry, nuclear PTEN expression was observed in approximately half of EndoCA patient tumors, independent of grade and cytoplasmic PTEN expression. Higher levels of the DNA damage response (DDR) marker, yH2AX, were observed by immunohistochemistry and immunofluorescence in human EndoCA tumor sections that were PTEN-negative, in murine EndoCA tissues that were genetically modified to be PTEN-null, and in Ishikawa EndoCA cells, which do not express endogenous PTEN. Over-expression of exogenous PTEN-WT or PTEN-NLS, a modified PTEN with an added nuclear localization signal, significantly improved both DDR and G2/M transition in Ishikawa cells treated with a DNA damaging agent. Whereas PARP inhibition with Olaparib was not as effective in Ishikawa cells expressing native or PTEN-NLS, inhibition with Talazoparib was not affected by PTEN overexpression. These results suggest that nuclear PTEN subcellular localization in human EndoCA could be diagnostic when considering DDR therapeutic intervention.

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Histamine H 3 receptor density is negatively correlated with neural activity related to working memory in humans

Abstract

Background

The histamine H₃ receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H₃ receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H₃ receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H₃ receptors in the prefrontal cortex.

Findings

Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H₃ receptor density was measured with the selective PET radioligand [¹¹C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H₃ receptors in this region.

Conclusions

Higher neural activity of working memory was associated with lower H₃ receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H₃ receptors in working memory and indicates the potential of H₃ receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

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EWS/ETS-driven Ewing Sarcoma requires BET bromodomain proteins

The EWS/ETS fusion transcription factors drive Ewing sarcoma (EWS) by orchestrating an oncogenic transcription program. Therapeutic targeting of EWS/ETS has been unsuccessful; however, identifying mediators of the EWS/ETS function could offer new therapeutic options. Here we describe the dependency of EWS/ETS-driven transcription upon chromatin reader BET bromdomain proteins and investigate the potential of BET inhibitors in treating EWS. EWS/FLI1 and EWS/ERG were found in a transcriptional complex with BRD4, and knockdown of BRD2/3/4 significantly impaired the oncogenic phenotype of EWS cells. RNA-seq analysis following knockdown or inhibition of BRD4 with JQ1 revealed an attenuated EWS/ETS transcriptional signature. In contrast to previous reports, JQ1 reduced proliferation and induced apoptosis through MYC-independent mechanisms without affecting EWS/ETS protein levels; this was confirmed by depleting BET proteins using PROTAC-BET degrader (BETd). Polycomb repressive complex 2 (PRC2)-associated factor PHF19 was downregulated by JQ1/BETd or BRD4 knockdown in multiple EWS lines. EWS/FLI1 bound a distal regulatory element of PHF19, and EWS/FLI1 knockdown resulted in downregulation of PHF19 expression. Deletion of PHF19 via CRISPR-Cas9 resulted in a decreased tumorigenic phenotype, a transcriptional signature that overlapped with JQ1 treatment, and increased sensitivity to JQ1. PHF19 expression was also associated with worse prognosis in Ewing sarcoma patients. In vivo, JQ1 demonstrated anti-tumor efficacy in multiple mouse xenograft models of EWS. Together these results indicate that EWS/ETS requires BET epigenetic reader proteins for its transcriptional program and can be mitigated by BET inhibitors. This study provides a clear rationale for the clinical utility of BET inhibitors in treating Ewing sarcoma.

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Flightless-I blocks p62-mediated recognition of LC3 to impede selective autophagy and promote breast cancer progression

p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded development of mammary tumors in PyVT mice. FliI induced p62-recruited cargoes into Triton X-100 insoluble fractions (TI) to form aggregates, thereby blocking p62 recognition of LC3 and hindering p62-dependent selective autophagy. This function of Flil was reinforced by Akt-mediated phosphorylation at Ser436 and inhibited by phosphorylation of Ulk1 at Ser64. Obstruction of autophagic clearance of p62-recruited cargoes by FliI was associated with the accumulation of oxidative damage on proteins and DNA, which could contribute to the development of cancer. Heterozygous knockout of FliI facilitated selectively autophagic clearance of aggregates, abatement of ROS levels, and protein oxidative damage, ultimately retarding mammary cancer progression. In clinical breast cancer samples, Akt-mediated phosphorylation of FliI at Ser436 negatively correlated with long-term prognosis, while Ulk1-induced FliI phosphorylation at Ser64 positively correlation with clinical outcome. Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer.

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Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission i.e. dynamics. Expression of ubiquitination-defective SNPH mutant Lys111→Arg or Lys153→Arg increased the speed and distance traveled by mitochondria, repositioned mitochondria to the cortical cytoskeleton, and supported heightened tumor chemotaxis, invasion, and metastasis in vivo. Interference with SNPH ubiquitination activated mitochondrial dynamics, resulting in increased recruitment of the fission regulator dynamin-related protein-1 (Drp1) to mitochondria, and Drp1-dependent tumor cell motility. These data uncover non-degradative ubiquitination of SNPH as a key regulator of mitochondrial trafficking and tumor cell motility and invasion. In this way, SNPH may function as a unique, ubiquitination-regulated suppressor of metastasis

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Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy

PURPOSE: In the proper context, radiation therapy (RT) can promote anti-tumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), impacts adaptive immune responses and combinatorial efficacy of RT with immune checkpoint blockade (ICB). EXPERIMENTAL DESIGN: We developed a preclinical model to compare stereotactic RT (Tumor RT) with or without ENI to examine immunological differences between RT techniques that spare or irradiate the DLN. RESULTS: Tumor RT was associated with up-regulation of an intratumoral T-cell chemoattractant chemokine signature (CXCR3, CCR5-related) that resulted in robust infiltration of antigen-specific CD8+ effector T-cells as well as FoxP3+ regulatory T-cells (Tregs). The addition of ENI attenuated chemokine expression, restrained immune infiltration and adversely impacted survival when combined with ICB, especially with anti-CLTA4 therapy. The combination of stereotactic RT and ICB led to long-term survival in a subset of mice and was associated with favorable CD8 effector-to-Treg ratios and increased intratumoral density of antigen-specific CD8+ T-cells. While RT technique (Tumor RT vs. ENI) impacted initial tumor control and survival, the ability to reject tumor upon re-challenge was partially dependent upon the mechanism of action of ICB; as RT/anti-CTLA4 was superior to RT/anti-PD-1. CONCLUSIONS: Our results highlight that irradiation of the DLN restrains adaptive immune responses through altered chemokine expression and CD8+ T-cell trafficking. These data have implications for combining RT and ICB, long-term survival and induction of immunological memory. Clinically, the immunomodulatory effect of the RT strategy should be considered when combining stereotactic RT with immunotherapy.

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Disruption of a -35kb enhancer impairs CTCF binding and MLH1 expression in colorectal cells

Purpose: MLH1 is a major tumour suppressor gene involved in the pathogenesis of Lynch syndrome and various sporadic cancers. Despite their potential pathogenic importance, genomic regions capable of regulating MLH1 expression over long distances have yet to be identified. Experimental Design: Here we use chromosome conformation capture (3C) to screen a 650-kb region flanking the MLH1 locus to identify interactions between the MLH1 promoter and distal regions in MLH1 expressing and non-expressing cells. Putative enhancers were functionally validated using luciferase reporter assays, chromatin immunoprecipitation and CRISPR-Cas9 mediated deletion of endogenous regions. To evaluate whether germline variants in the enhancer might contribute to impaired MLH1 expression in patients with suspected Lynch syndrome, we also screened germline DNA from a cohort of 74 patients with no known coding mutations or epimutations at the MLH1 promoter. Results: A 1.8kb DNA fragment, 35kb upstream of the MLH1 transcription start site enhances MLH1 gene expression in colorectal cells. The enhancer was bound by CTCF and CRISPR-Cas9 mediated deletion of a core binding region impairs endogenous MLH1 expression. 5.4% of suspected Lynch syndrome patients have a rare single nucleotide variant (G>A; rs143969848; 2.5% in gnomAD European, non-Finnish) within a highly conserved CTCF binding motif, which disrupts enhancer activity in SW620 colorectal carcinoma cells. Conclusions: A CTCF bound region within the MLH1-35 enhancer regulates MLH1 expression in colorectal cells and is worthy of scrutiny in future genetic screening strategies for suspected Lynch syndrome associated with loss of MLH1 expression.

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MET-oncogenic and JAK2-inactivating alterations are independent factors that affect regulation of PD-L1 expression in lung cancer

Purpose:The blockade of immune checkpoints such as PD-L1 and PD-1 is being exploited therapeutically in several types of malignancies. Here, we aimed to understand the contribution of the genetics of lung cancer (LC) to the ability of tumor cells to escape immunosurveillance checkpoints. Experimental Design: Over 150 primary non-small cell lung cancers, including pulmonary sarcomatoid carcinomas, were tested for the levels of HLA-I complex, PD-L1, tumor-infiltrating CD8+ lymphocytes and alterations in main LC genes. Correlations were validated in cancer cell lines using appropriate treatments to activate or inhibit selected pathways. We also performed RNA sequencing to assess changes in gene expression after these treatments Results: MET-oncogenic activation tended to associate with positive PD-L1 immunostaining, whereas STK11 mutations were correlated with negative immunostaining. In MET-altered cancer cells, MET triggered a transcriptional increase of PD-L1 that was independent of the IFN-mediated JAK/STAT pathway. The activation of MET also up-regulated other immunosuppressive genes (PDCD1LG2 and SOCS1), and transcripts involved in angiogenesis (VEGFA and NRP1) and in cell proliferation. We also report recurrent inactivating mutations in JAK2 that co-occur with alterations in MET and STK11, which prevented the induction of immunoresponse-related genes following treatment with IFN. Conclusions: We show that MET activation promotes the expression of several negative checkpoint regulators of the immunoresponse, including PD-L1. In addition, we report inactivation of JAK2 in LC cells that prevented the response to IFN. These alterations are likely to facilitate tumor growth by enabling immune tolerance and may affect the response to immune checkpoint inhibitors.

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Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer

Purpose: The accumulation of emergent RAS mutations during anti-epidermal growth factor receptor (EGFR) therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status. Experimental Design: This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the PlasmaSelect-R™ 64-gene panel at 0.1% sensitivity. Results: Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS. Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival (OS) for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval: 11.5-15.4) and 7.9 months (6.4-9.6), respectively (P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations. Conclusions: Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations.

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Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations

Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1.

Experimental Design: We analyzed the relationship between age, response to anti-PD1, and prior therapy in 538 patients. We used mouse models of melanoma, to analyze the intratumoral immune microenvironment in young versus aged mice and confirmed our findings in human melanoma biopsies.

Results: Patients over the age of 60 responded more efficiently to anti-PD-1, and likelihood of response to anti-PD-1 increased with age, even when we controlled for prior MAPKi therapy. Placing genetically identical tumors in aged mice (52 weeks) significantly increased their response to anti-PD1 as compared with the same tumors in young mice (8 weeks). These data suggest that this increased response in aged patients occurs even in the absence of a more complex mutational landscape. Next, we found that young mice had a significantly higher population of regulatory T cells (Tregs), skewing the CD8⁺:Treg ratio. FOXP3 staining of human melanoma biopsies revealed similar increases in Tregs in young patients. Depletion of Tregs using anti-CD25 increased the response to anti-PD1 in young mice.

Conclusions: While there are obvious limitations to our study, including our inability to conduct a meta-analysis due to a lack of available data, and our inability to control for mutational burden, there is a remarkable consistency in these data from over 500 patients across 8 different institutes worldwide. These results stress the importance of considering age as a factor for immunotherapy response. Clin Cancer Res; 1–10. ©2018 AACR.

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Correction: Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild-type metastatic colorectal carcinoma

Correction: Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild-type metastatic colorectal carcinoma

Correction: Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild-type metastatic colorectal carcinoma, Published online: 14 June 2018; doi:10.1038/s41416-018-0130-x

Correction: Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild-type metastatic colorectal carcinoma

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G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS

G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS

G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS, Published online: 14 June 2018; doi:10.1038/s41416-018-0137-3

G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS

https://ift.tt/2JQPg5V

TGFβ shuts the door on T cells

TGFβ shuts the door on T cells

TGFβ shuts the door on T cells, Published online: 14 June 2018; doi:10.1038/s41416-018-0122-x

TGFβ shuts the door on T cells

https://ift.tt/2JQPdqL

Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies

Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies

Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies, Published online: 14 June 2018; doi:10.1038/s41416-018-0105-y

Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies

https://ift.tt/2LONXlA

Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial

Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial

Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial, Published online: 14 June 2018; doi:10.1038/s41416-018-0036-7

Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial

https://ift.tt/2HMC3pN

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies, Published online: 14 June 2018; doi:10.1038/s41416-018-0125-7

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

https://ift.tt/2JQPfin

Correction: Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild-type metastatic colorectal carcinoma

https://ift.tt/2JLtcGC

Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial

https://ift.tt/2JyEH8g

G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS

https://ift.tt/2y8HqQN

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

https://ift.tt/2JBzUmH

Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies

https://ift.tt/2JJ00jL

TGFβ shuts the door on T cells

https://ift.tt/2MopR23

Moyamoya disease in a Moroccan baby: a case report

A stroke in a baby is uncommon, recent studies suggested that their incidence is rising. Moyamoya disease is one of the leading causes of stroke in babies. This condition is mostly described in Japan. In Moroc...

https://ift.tt/2HNxtaF

An overview on personalisation of radiotherapy prescriptions in locally advanced non-small cell lung cancer: Are we there yet?

Standard of care radiotherapy in LA-NSCLC is 60–66 Gy in 30–33 fractions. However outcomes for these patients are poor with 5-year survival in the range of 10–20%. Randomised controlled trials have shown that dose escalation in a linear fashion does not improve outcomes for all patients, thus there is a need to tailor the prescription to the individual patient. This review assesses the strategies published to personalise the radiation therapy dose prescription in LA-NSCLC. A systematic and scoping search of the literature was performed to identify studies that met the inclusion criteria.

https://ift.tt/2t6w7mj

Evaluation of D-isomers of 4-borono-2- 18 F-fluoro-phenylalanine and O - 11 C-methyl-tyrosine as brain tumor imaging agents: a comparative PET study with their L-isomers in rat brain glioma

Abstract

Background

The potential of the D-isomerization of 4-borono-2-¹⁸F-fluoro-phenylalanine (¹⁸F-FBPA) to improve its target tumor to non-target normal brain tissue ratio (TBR) was evaluated in rat brain glioma and compared with those of L- and D-¹¹C-methyl-tyrosine (¹¹C-CMT).

The L- or D-isomer of ¹⁸F-FBPA was injected into rats through the tail vein, and their whole body kinetics and distributions were assessed using the tissue dissection method up to 90 min after the injection. The kinetics of L- and D-¹⁸F-FBPA or L- and D-¹¹C-CMT in the C-6 glioma-inoculated rat brain were measured for 90 or 60 min, respectively, using high-resolution animal PET, and their TBRs were assessed.

Results

Tissue dissection analyses showed that D-¹⁸F-FBPA uptake was significantly lower than that of L-¹⁸F-FBPA in the brain and abdominal organs, except for the kidney and bladder, reflecting the faster elimination rate of D-¹⁸F-FBPA than L-¹⁸F-FBPA from the blood to the urinary tract. PET imaging using ¹⁸F-FBPA revealed that although the brain uptake of D-¹⁸F-FBPA was significantly lower than that of L-¹⁸F-FBPA, the TBR of the D-isomer improved to 6.93 from 1.45 for the L-isomer. Similar results were obtained with PET imaging using ¹¹C-CMT with a smaller improvement in TBR to 1.75 for D-¹¹C-CMT from 1.33 for L-¹¹C-CMT.

Conclusions

The present results indicate that D-¹⁸F-FBPA is a better brain tumor imaging agent with higher TBR than its original L-isomer and previously reported tyrosine-based PET imaging agents. This improved TBR of D-¹⁸F-FBPA without any pre-treatments, such as tentative blood-brain barrier disruption using hyperosmotic agents or sonication, suggests that the D-isomerization of BPA results in the more selective accumulation of ¹⁰B in tumor cells that is more effective and less toxic than conventional L-BPA.

https://ift.tt/2HJ9fyl

Stent-induced compression necrosis for the endoscopic removal of a partially eroded Lap-Band

Endoscopic removal of eroded Lap-Bands is a minimally invasive alternative to surgical removal that prerequires sufficient erosion through the gastric wall, that is, ≥180° of the gastro-oesophageal wall circumference. A 69-year-old woman presented with dysphagia due to a long-standing Lap-Band erosion, currently of a 60° circumference. Adhesions due to her extensive surgical history rendered surgical treatment undesirable, so a self-expanding stent was placed endoscopically to induce sufficient erosion for subsequent endoscopic removal. During therapy, the patient complained of ructus and dysphagia, probably related to an overly proximally (oesophageal) positioned stent. After a total of 12 weeks, far longer than the described stenting duration in the literature, the Lap-Band was found free in the gastric lumen and was successfully removed using an endoscopic loop. Stent-induced compression necrosis should be considered as a minimally invasive treatment option for Lap-Bands eroded for <180°, with caution in the context of extensive fibrosis.

https://ift.tt/2JGbRPl

Phlegmasia cerulea dolens presenting with acute compartment syndrome and pulmonary embolism

Description 

A 50-year-old woman, a known diabetic and hypertensive with poor compliance to treatment, presented with fever, dyspnoea and left-sided pleuritic chest pain for 15 days and left lower limb swelling worsening over the past 1 week. On examination, her vitals were stable, and she had significant left lower limb oedema extending up to the upper thigh with livedo reticularis (figure 1). The left lower limb pulses were not palpable. There was excruciating pain on light touch and passive flexion of the toes and ankle. Urgent arterial and venous Doppler sonography of the lower limbs revealed a left-sided iliofemoral venous thrombus. With the clinical diagnosis of acute compartment syndrome, urgent single incision four compartment fasciotomy was performed.

Figure 1

(A) Clinical examination at the time of admission showing lower limb oedema with livedo reticularis, (B) left lower leg livedo reticularis with superficial blistering (white arrow) and (C)...

https://ift.tt/2Mmz4YR

Spontaneous tumour lysis syndrome in small cell lung cancer: a rare phenomenon

Tumour lysis syndrome (TLS) is an oncological emergency. It is caused by cellular death occurring secondary to cancer therapy or spontaneously in rapidly dividing tumours. More common in haematological malignancies, it has also been reported in solid tumours. Out of 14 cases of small cell lung cancer (SCLC) with TLS, only three cases of spontaneous TLS have been reported in literature to date. Here we report a case of SCLC presenting as a spontaneous TLS.

https://ift.tt/2y7nwpc

Fulminant pulmonary embolism with fatal outcome in a patient with low clinical prediction scores

We present a case of a 72-year-old man with submassive acute pulmonary thromboembolism. Pulmonary embolism severity index Score and common clinical risk stratification recommended systemic anticoagulation and a clinical course without complications was expected. A primary reperfusion strategy was not indicated by the current guidelines. Under established anticoagulation, the patient was found in cardiac arrest immediately after mobilisation from the bed the next morning. Right heart catheterisation under ongoing resuscitation revealed a complete obstruction of the right pulmonary artery by a big thrombus. Catheter-directed intervention trying to bypass the thrombus with interventional guidewires failed. Ultimately, the patient died from acute right heart failure. The current case raises concern that the prediction scores available for pulmonary embolism may insufficiently predict short-term outcome in isolated patients.

https://ift.tt/2MiGbBv

Giant choledochal cyst presenting during third trimester of pregnancy

Biliary cystic disease is a rare entity. Twenty-five per cent of cases are diagnosed during adulthood and only a few reports have described this condition during pregnancy, where it represents a therapeutic challenge for both obstetricians and surgeons with regard to the risks it entails for the patient and the fetus.

Definitive management is surgical resection, as cysts may progress to malignancy if untreated. During pregnancy, resection is generally deferred to after delivery, especially in the context of suspected cholangitis.

A 19-year-old young woman with no previous prenatal control, presented to the emergency department on her 32nd week of gestation with abdominal pain and jaundice. A giant Todani I biliary cyst was observed on imaging along with dilation of the proximal biliary tree suggesting acute cholangitis. Fetal compromise prompted immediate delivery after which percutaneous biliary drainage was performed. Following recovery, the cyst was surgically resected.

https://ift.tt/2JLufql

Circumcaval ureter/retrocaval ureter

Description  

A 33-year-old non-diabetic married woman from rural background presented with complaints of dull intermittent right flank pain since 1 year. She had no history of fever, dysuria, haematuria or weight loss. Clinical examination of the abdomen was within normal limits. Complete laboratory evaluation including urinalysis, complete blood picture, urea, creatinine and electrolytes were within normal limits. Ultrasonography (USG) of kidney, ureters and bladder showed moderate hydroureteronephrosis (HDUN) until right midureter. Intravenous pyelography (IVP) revealed dilated right renal pelvicalyceal system and upper ureter with abrupt S-shaped turn of ureter at the level of L4 vertebrae.

The appearance on IVP was strongly suspicious of retrocaval ureter and hence a contrast-enhanced CT urography was performed to confirm the diagnosis, which showed dilated right proximal ureter (figure 1) coursing medially and lying posterior to inferior vena cava (IVC). Three-dimensional reconstruction from CT urography showed proximal HDUN and classical S-shaped loop of the ureter behind the IVC...

https://ift.tt/2MiG88N

Aortopulmonary window with pumonary atresia with ventricular septal defect with D-transposition of great arteries: extremely rare anomaly

Aortopulmonary window (APW) is rare a congenital heart disease accounting for 0.1%–0.2% of all congenital heart defects. The 35% of the APW has been associated with wide variety of other structural heart diseases such as ventricular septal defect, persistent ductus arteriosus, arch anomalies and coronary artery anomalies. To the best of our knowledge, only six cases of APW with pulmonary atresia with ventricular septal defect has been described in the literature. It resembles the type 1 truncus arteriosus, and differentiation from this condition is important prior to surgical correction. We present a case of 14-year-old girl child; she was diagnosed with APW with pulmonary atresia with ventricular septal defect and D transposition of great arteries with the help of echocardiography, cardiac catheterisation and cardiac CT.

https://ift.tt/2JGbHrd

The absolute lymphocyte count can predict the overall survival of patients with non-small cell lung cancer on nivolumab: a clinical study

Abstract

Introduction

The neutrophil-to-lymphocyte (ANC/ALC) ratio is associated with worse prognosis in patients with NSCLC on immunotherapies, but the role of ALC remains unclear. The previous radiation therapy causes lymphopenia, and given approaches of combining radiation with immunotherapies, it is critical to better understand the impact of peripheral lymphocytes.

Patients and methods

We evaluated retrospectively 22 patients with advanced NSCLC treated with nivolumab at Boston Medical Center from January 2014 to September 2016 and correlated the peripheral blood counts with the overall survival (OS) and overall time on treatment. We assessed the effect of the previous radiation on peripheral blood counts and clinical outcomes.

Results

Baseline ALC and ANC/ALC ratios are positively and negatively correlated, respectively, with the OS on nivolumab. The ALC and ALC/WBC ratios at 6 weeks on treatment are positively associated with the OS. Kaplan–Meier analysis at baseline and at 6 weeks showed significantly increased OS in the group of patients with the highest ALC. The previous radiation therapy was positively correlated with the ANC and negatively correlated with the ALC/WBC ratio at 8 weeks after the initiation of nivolumab.

Conclusion

Our finding that ALC at baseline and at 6 weeks on treatment is positively correlated with the OS provides an easily obtained predictive marker. Our result that the previous radiation is associated with higher ANC and lower ALC during treatment supports that the combination of radiation therapy with immunotherapy should be carefully applied and potentially peripheral blood counts can be utilized to stratify patients for this approach.

https://ift.tt/2JBpT8S

Zoledronate increases enrichment, activation and expansion of natural killer cells from umbilical cord blood

https://ift.tt/2t5Axd8

Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models

Abstract

Background

Sym004 is a mixture of two monoclonal antibodies (mAbs), futuximab and modotuximab, targeting non-overlapping epitopes on the epidermal growth factor receptor (EGFR). Previous studies have shown that Sym004 is more efficient at inducing internalization and degradation of EGFR than individual components, which translates into superior cancer cell inhibition. We investigated whether Sym004 induces removal of EGFRvIII and if this removal translates into tumor growth inhibition in hard-to-treat glioblastomas (GBMs) harboring the mutated, constitutively active EGFR variant III (EGFRvIII).

Methods

To address this question, we tested the effect of Sym004 versus cetuximab in eight patient-derived GBM xenograft models expressing either wild-type EGFR (EGFRwt) and/or mutant EGFRvIII. All models were tested as both subcutaneous and orthotopic intracranial xenograft models.

Results

In vitro studies demonstrated that Sym004 internalized and removed EGFRvIII more efficiently than mAbs, futuximab, modotuximab, and cetuximab. Removal of EGFRvIII by Sym004 translated into significant in vivo anti-tumor activity in all six EGFRvIII xenograft models. Furthermore, the anti-tumor activity of Sym004 in vivo was superior to that of its individual components, futuximab and modotuximab, suggesting a clear synergistic effect of the mAbs in the mixture.

Conclusion

These results demonstrate the broad activity of Sym004 in patient-derived EGFRvIII-expressing GBM xenograft models and provide a clear rationale for clinical evaluation of Sym004 in EGFRvIII-positive adult GBM patients.

https://ift.tt/2y5KuNe

Characteristics of time-activity curves obtained from dynamic 11 C-methionine PET in common primary brain tumors

Abstract

Purpose

The aim of this study was to assess whether dynamic PET with ¹¹C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors.

Methods

One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE).

Results

The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P < 0.05). The SLOPE in the late phase was significantly lower in tumors that included an oligodendroglial component compared to astrocytic tumors (P < 0.001). When we set the cutoff of the SLOPE in the late phase to − 0.04 h⁻¹ for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731.

Conclusions

The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

https://ift.tt/2JzKhHL

The breast graded prognostic assessment is associated with the survival outcomes in breast cancer patients receiving whole brain re-irradiation

Abstract

Introduction

Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation.

Methods

Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed. Patients were divided according to the 4 molecular subtypes of luminal A/B (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]−), luminal HER2 (HR+/HER2+), HER2 (HR−/HER2+), and triple negative (HR−/HER2−). The clinical and radiological responses and survival rates after WB re-irradiation were analyzed.

Results

At 1 month after WB re-irradiation, 13 of 23 patients (56.5%) exhibited disappearance or alleviation of neurological symptoms. The median survival time after WB re-irradiation was 2.93 months (95% confidence interval [CI], 1.79–4.08). After WB re-irradiation, patients with HER2-negative tumors had poorer median survival times than those with HER2-positive tumors (2.23 vs. 3.0 months, respectively; p = 0.022). Furthermore, patients with high breast GPA scores (2.5–4.0, n = 11) had longer median survivals than those with low-scores (0–2.0, n = 12) after WB re-irradiation (4.37 vs. 1.57 months, respectively; p < 0.005).

Conclusions

WB re-irradiation may be a feasible treatment option for certain breast cancer patients who develop brain metastatic lesions after first-course WBRT when these lesions are ineligible for radiosurgery or surgery.

https://ift.tt/2y6EDaB

ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation

Abstract

Glioblastoma (GBM) is a highly fatal disease with a 5 year survival rate of less than 22%. One of the most effective treatment regimens to date is the use of radiotherapy which induces lethal DNA double-strand breaks to prevent tumour growth. However, recurrence occurs in the majority of patients and is in-part a result of robust radioresistance mechanisms. In this study, we demonstrate that the multifunctional cytokine, interleukin-6 (IL-6), confers a growth advantage in GBM cells but does not have the same effect on normal neural progenitor cells. Further analysis showed IL-6 can promote radioresistance in GBM cells when exposed to ionising radiation. Ablation of the Ataxia-telangiectasia mutated serine/threonine kinase that is recruited and activated by DNA double-strand breaks reverses the effect of radioresistance and re-sensitised GBM to DNA damage thus leading to increase cell death. Our finding suggests targeting the signaling cascade of DNA damage response is a potential therapeutic approach to circumvent IL-6 from promoting radioresistance in GBM.

https://ift.tt/2JyU3tw

Molecular profiles for insular low-grade gliomas with putamen involvement

Abstract

Background

The newly proposed putamen classification system shows good prognostic value in patients with insular LGGs, yet no study towards the molecular profiles of putamen involved LGGs has been proposed.

Methods

Clinical information and imaging data of patients diagnosed with insular low-grade gliomas were collected retrospectively. Genetic information of the 34 tumors was assessed using RNA-sequencing. Gene set enrichment analysis was further performed to identify the genes showing differential expression between putamen-involved tumors and putamen non-involved tumors. The level of Ki-67 expression was also evaluated.

Results

There were 843 genes identified to be differentially expressed between putamen-involved and non-involved gliomas. Specifically, Gene set enrichment analysis discovered 13 Kyoto Encyclopedia of Genes and Genomes pathways and 37 Gene Ontology Biological Process term were upregulated in putamen-involved low-grade glioma cells. The enriched GO sets with the highest gene counts included cell cycle (42 genes), mitotic cell cycle (24 genes), and cell division (19 genes). Furthermore, high expression of Ki-67 was associated with putamen involvement in insular gliomas.

Conclusions

There is clear genetic variation between putamen-involved and non-involved insular low-grade gliomas. The differential expression of genes related to the processes of cell proliferation, cell migration, or DNA repair may lead to putamen involvement. The findings suggest that among the two subtypes, putamen-involved insular low-grade gliomas have higher malignancy, and the clinical treatment towards the putamen-involved insular low-grade gliomas should be more active.

https://ift.tt/2y7bCeX

Correction to: Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood

The therapeutic experience reported in the paper was conceived after the use of nimotuzumab and radiotherapy (BSCPED-05 international multicentric trial, EUDRACT 2005-003100-11) in 2009 when we decided to explore the activity of the same combination plus vinorelbine (see the paper for the rationale).

https://ift.tt/2JzJJBH

Correction to: ATP binding cassette (ABC) transporters: expression and clinical value in glioblastoma

Abstract

The names of authors Marc Sanson and Jean-Yves Delattre were incorrectly presented in the initial online publication. The original article has been corrected.

https://ift.tt/2JIoxp4

Malignancy probability map as a novel imaging biomarker to predict malignancy distribution: employing MRS in GBM patients

Abstract

The main aim of this study was to propose a new statistical method for evaluation of spatial malignancy distribution within Magnetic Resonance Spectroscopy (MRS) grid in Glioblastoma Multiforme patients. Voxels with different malignancy probabilities were presented as a novel MRS-based Malignancy Probability Map (MPM). For this purpose, a predictive probability-based clustering approach was developed, including the two following steps: (1) Gaussian Mixture Model, (2) Quadratic Discriminate Analysis coupled with Genetic Algorithm. Clustered probability values from two methods were then integrated to exploit the MPM. Results show that the suggested method is able to estimate the malignancy distribution with over 90% sensitivity and specificity. The proposed MRS-based MPM has an acceptable accuracy for providing useful complementary information about regional diffuse glioma malignancy, with the potential to lead to better detection of tumoral regions with high probability of malignancy. So, it also may encourage the use of additional information of this map as a tool for dose painting.

https://ift.tt/2MoiWG0

Location of subventricular zone recurrence and its radiation dose predicts survival in patients with glioblastoma

Abstract

Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement. Survival was compared based on recurrence type, distance from the initial enhancing tumor (local ≤ 2 cm, distant > 2 cm), and the radiation dose at the recurrence site. Progression of enhancing subventricular tumor was common at both local (58%) and distant (42%) sites. Median survival was better after local SVZ recurrence than distant SVZ recurrence (8.7 vs. 4.3 months, p = 0.04). Radiation doses at local SVZ recurrence sites recurrence averaged 57.0 ± 4.0 Gy compared to 44.7 ± 6.7 Gy at distant SVZ recurrence sites (p = 0.008). Distant subventricular progression at a site receiving ≤ 45 Gy predicted worse subsequent survival (p = 0.05). Glioblastomas frequently recurred in the subventricular zone, and patient survival was worse when enhancing tumor occurred at sites that received lower radiation doses. This recurrent disease may represent disease undertreated at the time of diagnosis, and further study is needed to determine if improved treatment strategies, such as including the subventricular zone in radiation fields, could improve clinical outcomes.

https://ift.tt/2y7bwnB

The safety of magnetic resonance imaging-guided laser interstitial thermal therapy for cerebral radiation necrosis

Abstract

Cerebral radiation necrosis (CRN) is a known complication of radiation therapy. Treatment options are limited and include steroids, bevacizumab, and surgery. This study seeks to determine the safety of laser interstitial thermal therapy (LITT) for CRN and identify the pattern of post-ablation volume change over time. Patients undergoing LITT for tumor treatment at Henry Ford Hospital between November 2013 and January 2016 with biopsy-confirmed CRN were prospectively collected and retrospectively reviewed with attention to ablation volume, survival, demographic data, steroid dose, and complications. Imaging occurred at set intervals beginning pre-ablation. Ten patients with 11 ablations were evaluated. Four patients had a primary diagnosis of high-grade glioma, while six had metastatic lesions. An average of 86% of CRN volume was ablated. Ablation volume increased to 430% of initial CRN volume at 1–2 weeks before decreasing to 69% after 6 months. No patient had a decline in baseline neurological examination while in the hospital. Four patients developed delayed neurological deficits likely due to post-operative edema, of which three improved back to baseline. The 6-month survival was 77.8% and the 1-year survival was 64.8% based on Kaplan–Meier curve estimates. In this study, LITT was a relatively safe treatment for CRN, providing both a diagnostic and therapeutic solution for refractory patients. Significant increase in ablation volume was noted at 1–2 months, gradually decreasing in size to less than the original volume by 6 months. Further studies are needed to better define the role of LITT in the treatment of CRN.

https://ift.tt/2JvOMCW

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma

Abstract

Purpose

This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design.

Experimental design

Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m², daily) followed by TMZ maintenance (100–200 mg/m²/day, days 1–5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8).

Results

Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65–1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85–1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3–4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%.

Conclusions

TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

https://ift.tt/2y7BmaW

Indications for salvage surgery during treatment for intracranial germ cell tumors

Abstract

This study retrospectively reviewed our single institute experience to clarify the optimal indication and timing of salvage surgery. Retrospective analysis of 159 consecutive cases with germ cell tumors identified 20 cases with salvage surgery. These cases were classified based on the radiological response to neoadjuvant treatment before salvage surgery into increase (growing group, five cases), no change (stable group, seven cases), and decrease (shrinkage group, eight cases) in tumor size. Changes in tumor markers, histological findings, and the pattern of failure after salvage surgery were reviewed. Growing teratoma syndrome (GTS) is defined as enlargement of tumor consisting of mature teratoma after chemotherapy with normalization of tumor markers. In growing group, two cases presented GTS, whereas other three cases did not fulfill the criteria for GTS. All cases in stable and shrinkage group had elevated levels of tumor markers at presentation and decreased levels after neoadjuvant treatment. Histologically, sparse components of mature teratoma with extensive fibrosis were found in cases with GTS and seven of eight cases in shrinkage group, whereas mature teratoma without fibrosis was found in six of seven cases in stable group. Six cases recurred after salvage surgery. We identified three factors as risks for recurrence after salvage surgery, as follows: (1) growing lesion which did not fulfill the criteria for GTS, (2) non-normalized level of tumor marker before salvage surgery, and (3) residual germinoma component. In conclusion, salvage surgery is recommended for patients with GTS, or with normalized tumor markers in stable or shrinkage group.

https://ift.tt/2JyTM9Y

Incontinentia Pigmenti Misdiagnosed as Neonatal Herpes Simplex Virus Infection

Incontinentia pigmenti (IP) is an X-linked dominant neurocutaneous syndrome with ophthalmologic, neurologic, cutaneous, and dental manifestations and in most cases antenatally lethal in boys. Occasionally, typical IP may occur in boys due to Klinefelter syndrome or a genomic mosaicism. Skin lesions are observed in 4 stages: blistering, verrucous linear plaques, swirling macular hyperpigmentation, followed by linear hypopigmentation that develop during adolescence and early adulthood. Neonatal herpes simplex virus (HSV) infection can be manifested in 3 forms: localized, disseminated, and central nervous system (CNS) involvement. Timely diagnosis and treatment of neonatal HSV infection is critical. In this case report, we present a 12-day female newborn with a history of maternal genital HSV in second trimester and vesicular lesions on the upper and lower limbs that was appeared at first hours of life. She was admitted in the maternity hospital that was born and was treated by antibiotic and acyclovir for 11 days. Then, she readmitted for her distributed vesicular lesions. The results of blood and CSF for HSV PCR were negative. Eventually the diagnosis for incontinentia pigmenti was made by consultation with a dermatologist, and skin biopsy confirmed the diagnosis.

https://ift.tt/2JHK29w

Radial scar on image-guided breast biopsy: is surgical excision necessary?

Abstract

Purpose

Radial scar's stellate appearance may mimic carcinoma mammographically and histologically. Management of radial scar (RS) found on breast core needle biopsies (CNB) ranges from excision to clinical observation due to the variation in reported upgrades to malignancy at surgical excision. We examined the upgrade rate in patients with RS detected on CNB at our institution and reviewed the current literature.

Methods

A retrospective study was conducted of all cases with RS diagnosed on CNB between December 2006 and March 2017 at our institution. Inclusion criteria were patients with "pure" RS and RS associated with high-risk lesions (HRL). Upgrade was defined as invasive or non-invasive cancer in the excisional biopsy.

Results

157 cases were identified with RS on CNB, and 122 cases met inclusion criteria. Of these 122 cases, 91 (75%) had pure RS on CNB while 31 (25%) had associated atypia or HRL. 81 (66%) of patients proceeded to excisional biopsy and 41 (34%) did not. Two patients (1.6% of total) were found to have a low-grade invasive ductal carcinoma (0.6 and 0.8 cm) upon surgical excision. None of the remaining 120 patients developed an ipsilateral breast cancer with a mean of 32.3-month follow-up.

Conclusions

We found a very low upgrade rate to breast cancer when RS was found on CNB with or without associated HRL. Our results are consistent with other reported series. Our data do not support surgical excision for RS but rather close clinical follow-up for patients with RS on CNB.

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A parallel model for breast cancer metastasis

https://ift.tt/2MpaGpd

Receptor conversion in breast cancer patients with liver metastases after hepatectomy might affect survival

https://ift.tt/2LNBH4M

Prediction of breast cancer risk with volatile biomarkers in breath

Abstract

Background

Human breath contains volatile organic compounds (VOCs) that are biomarkers of breast cancer. We investigated the positive and negative predictive values (PPV and NPV) of breath VOC biomarkers as indicators of breast cancer risk.

Methods

We employed ultra-clean breath collection balloons to collect breath samples from 54 women with biopsy-proven breast cancer and 124 cancer-free controls. Breath VOCs were analyzed with gas chromatography (GC) combined with either mass spectrometry (GC MS) or surface acoustic wave detection (GC SAW). Chromatograms were randomly assigned to a training set or a validation set. Monte Carlo analysis identified significant breath VOC biomarkers of breast cancer in the training set, and these biomarkers were incorporated into a multivariate algorithm to predict disease in the validation set. In the unsplit dataset, the predictive algorithms generated discriminant function (DF) values that varied with sensitivity, specificity, PPV and NPV.

Results

Using GC MS, test accuracy = 90% (area under curve of receiver operating characteristic in unsplit dataset) and cross-validated accuracy = 77%. Using GC SAW, test accuracy = 86% and cross-validated accuracy = 74%. With both assays, a low DF value was associated with a low risk of breast cancer (NPV > 99.9%). A high DF value was associated with a high risk of breast cancer and PPV rising to 100%.

Conclusion

Analysis of breath VOC samples collected with ultra-clean balloons detected biomarkers that accurately predicted risk of breast cancer.

https://ift.tt/2JLKXsG

Pre-operative progesterone benefits operable breast cancer patients by modulating surgical stress

Abstract

Purpose

We have reported a survival benefit of single injection of hydroxyprogesterone prior to surgery for primary tumour in patients with node-positive operable breast cancer. Hydroxyprogesterone was meant to recapitulate the luteal phase of menstrual cycle in these women. We wanted to understand the molecular basis of action of hydroxyprogesterone on primary breast tumours in a peri-operative setting.

Methods

We performed whole transcriptome sequencing (RNA-Seq) of primary breast tumour samples collected from patients before and after hydroxyprogesterone exposure and controls. Paired breast cancer samples were obtained from patients who were given hydroxyprogesterone before surgery and a group of patients who were subjected to only surgery.

Results

A test of significance between the two groups revealed 207 significantly altered genes, after correction for multiple hypothesis testing. We found significantly contrasting gene expression patterns in exposed versus unexposed groups; 142 genes were up-regulated post-surgery among exposed patients, and down-regulated post-surgery among unexposed patients. Significantly enriched pathways included genes that respond to progesterone, cellular stress, nonsense-mediated decay of proteins and negative regulation of inflammatory response. These results suggest that cellular stress is modulated by hydroxyprogesterone. Network analysis revealed that UBC, a mediator of stress response, to be a major node to which many of the significantly altered genes connect.

Conclusions

Our study suggests that pre-operative exposure to progesterone favourably modulates the effect of surgical stress, and this might underlie its beneficial effect when administered prior to surgery.

https://ift.tt/2HKxv3e

Thirty-day postoperative morbidity and mortality in elderly women with breast cancer: an analysis of the NSQIP database

Abstract

Purpose

Postoperative complication rates for elderly women undergoing breast cancer surgery have not been well studied. We describe the postoperative complication rates of elderly (≥ 70 years) women with breast cancer and compare them with young (40–69 years) women.

Methods

Data were extracted from the National Surgical Quality Improvement Program database (2004–2014). We included women with invasive breast cancer who underwent surgery. Outcomes were 30-day postoperative morbidity and mortality (complications), which were compared between young and elderly women. Morbidity was categorized using the Surgical Risk Preoperative Assessment System (SURPAS) clusters.

Results

We identified 100,037 women of which 26.7% were elderly. Compared to young women, elderly women were more likely to have more comorbidities and undergo breast-conserving surgery, but less likely to undergo lymph node surgery, breast reconstruction, and neoadjuvant chemotherapy. While the 30-day overall morbidity rate was not significantly different between young and elderly women (3.9 vs. 3.8%, p = 0.2), elderly women did have significantly higher rates of pulmonary, cardiac (arrest and myocardial infarction), venous thromboembolic, and neurological morbidity. Specific morbidities that showed significantly lower rates among elderly women included wound disruption and deep and organ space surgical site infection. Any cause death was significantly higher in elderly compared to young women (0.2 vs. 0.05%, p < 0.001).

Conclusions

While some specific 30-day postoperative morbidities were more often seen in elderly women, the overall 30-day postoperative complication rate was very low. These data support the safety of breast cancer surgery in well-selected elderly patients.

https://ift.tt/2JS133Y

Prognostic impact of surgery for early-stage invasive breast cancer on breast cancer-specific survival, overall survival, and recurrence risk: a population-based analysis

Abstract

Purpose

Recent cohort studies demonstrated better overall survival (OS) or breast cancer-specific survival (BCS) for breast-conserving therapy (BCT) followed by radiation (RT) compared to mastectomy alone (MT). This is the first observational study in which adjustments for a comprehensive set of prognostic factors, adjuvant therapies, mode of detection, and comorbidities were possible to investigate OS, BCS, as well as recurrence risk of patients undergoing BCT + RT, MT + RT, or MT.

Methods

Women aged 50–74 years at diagnosis of early-stage invasive breast cancer (I–IIIa) between 2001 and 2005 at the German population-based case–control study (MARIE study) were recruited and followed prospectively as a case cohort until 2015. Kaplan–Meier estimates and stepwise adjusted multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI).

Results

The 2762 patients included were followed up for a median of 11.9 years (95% CI 11.8–12.0). 74.2% of patients underwent BCT + RT; 10.3% MT + RT and 15.6% MT alone. Compared to patients treated with MT alone, patients treated with BCT + RT showed non-statistically significant improved OS (HR 0.79, 95% CI 0.61–1.02), BCS (HR 0.79, 95% CI 0.55–1.12), and no difference in recurrence risks (HR 1.01, 95% CI 0.74–1.37). For patients treated with MT + RT, there were no differences in OS (HR 1.06, 95% CI 0.75–1.50), BCS (HR 1.17, 95% CI 0.75–1.82), or recurrence risk (HR 1.33, 95% CI 0.89–1.97).

Conclusions

Among patients with early-stage breast cancer, clinical outcomes more than 10 years after diagnosis did not differ between the primary treatment options BCT + RT, MT + RT versus MT alone after full adjustment.

https://ift.tt/2sRx2ry

Comparison of breast cancers detected in the Verona screening program following transition to digital breast tomosynthesis screening with cancers detected at digital mammography screening

Abstract

Background

The Verona population-based breast cancer (BC) screening program provides biennial mammography to women aged 50–69 years. Based on emerging evidence of enhanced detection, the program transitioned to digital breast tomosynthesis (DBT) screening.

Methods

This is a prospective pilot evaluation of DBT with synthesised 2D mammography screening implemented during April 2015–March 2017; the rate and characteristics of cancers detected at DBT screening were compared with those detected at the preceding digital mammography (DM) screening round (April 2013–March 2015) in the same screening program. Distribution of imaging and tumour characteristics were compared.

Results

Amongst 34,071 women screened in the Verona DBT pilot, 315 BCs were detected; 153 BCs were detected amongst 29,360 women in the DM screening round. Estimated CDRs were 9.2/1000 (95% CI 8.3–10.3) DBT screens versus 5.2/1000 (95% CI 4.4–6.1) DM screens, P < 0.001. Statistically significant differences were found in the distribution of whether recall by one/both screen readers (more BCs recalled by both readers at DBT than DM); whether detected on one/two views (higher proportion detected on only one view at DBT than DM); type of radiological lesions; tumour stage, pT and histological categories (lower proportion of DCIS/pTis, higher proportions of pT1a and pT1b, and higher proportion of invasive cancers of special types, at DBT than DM); and tumour grade (higher proportion of grade I at DBT than DM). There were no differences in distributions of nodal and hormone receptor (ER/PR) status.

Conclusions

Our findings provide early insights into the extent that transitioning to DBT screening may modify the characteristics of screen-detected breast cancer to inform discussion regarding pros and cons of DBT screening; although our data provide some reassurance that DBT does not increase the proportion of screen-detected DCIS, they highlight mixed findings on comparative tumour characteristics, suggesting a potential for enhancing screening benefit and possibly also over-diagnosis from DBT screening.

https://ift.tt/2HKRIWR

Breast screening and the parallel progression model of cancer

https://ift.tt/2HLE2uy

Health-related quality of life of Iranian breast cancer patients: a meta-analysis and systematic review

Abstract

Purpose

Quality of life is the most important psychological factor affecting breast cancer patients. This study aimed to examine the health related quality of life of breast cancer patients in Iran.

Methods

International (PubMed, Web of science, Scopus and Google scholar) and national (SID, Magiran) databases were searched for related studies to September 2017. The quality of the articles was evaluated using the Hoy tool.

Results

Out of 232 initial studies, 18 studies performed on 2263 people were included in the final stage of the study. Based on the EORTC-QLQ-C30 and random effect method, the pooled mean score of quality of life in 1073 people was 57.88 (95% CI 48.26–67.41, I² = 97.90%) and the pooled mean score of quality of life based on WHOQOL-BREF in 357 people was 66.79 (95% CI 45.96–87.62, I² = 99.50%).

Conclusion

According to the results of the study, a moderate level of quality of life in women with breast cancer was indicated. Therefore, the use of multidimensional approaches can improve their quality of life.

https://ift.tt/2JMzCZl

Pigmented Epithelioid Melanocytoma (Animal Types of Melanoma) on the Nose

Pigmented epithelioid melanocytoma (PEM), also known as an animal-type melanoma, is a distinctive group of melanocytic tumors with a more favorable prognosis than conventional melanoma. Since tumor-associated macrophages (TAMs) extend in the premetastatic lymph nodes in several cancers, we hypothesized that the lower rate of lymph node metastasis in PEM might be correlated with the phenotypes of TAMs. Therefore, in this report, we further investigate the subpopulation of TAMs in PEM, revealing that the main population of TAMs in histiocytic lesion is CD163+CD206+PD-L1+ M2-polarized macrophages. In addition, since the PD-L1-expressing CD205+ dendritic cells are also detected in histiocytic lesions, the PD-L1-expressing TAMs and dendritic cells might suggest favorable prognostic factors in patients with PEM.
Case Rep Oncol 2018;11:378–382

https://ift.tt/2HKPOWd

Paraneoplastic Seronegative Pauci-Immune Glomerulonephritis Associated with Lung Adenocarcinoma Responds to Rituximab: A Case Report

Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of pauci-immune renal vasculitis. However, in 10% of the cases, ANCA are absent. We present a case of a 64-year-old man with a chronic untreated hepatitis C virus infection and Middle Eastern thalassemia who was ANCA-negative when he was hospitalized due to acute kidney injury and accounts for an uncommon presentation of renal vasculitis. The patient had earlier reported to have undergone local lobectomy and adjuvant chemotherapy (carboplatin/pemetrexed) for lung adenocarcinoma a month prior. IL-6 has been reported to be involved in the pathophysiological cascade causing pauci-immune glomerulonephritis amongst non-small cell lung cancer patients. Previous studies with subgroup analysis have demonstrated that ANCA negativity has been associated with more chronic glomerular lesions and less crescent formation, which tends to have a critical outcome in the renal system. However, our patient underwent kidney biopsy exhibiting active crescentic glomerulonephritis, pauci-immune type with 5 cellular crescents amongst 15 glomeruli. To our knowledge, this is the third reported case of ANCA-negative vasculitis with typical presentation on biopsy in non-small cell lung cancer patients.
Case Rep Oncol 2018;11:372–377

https://ift.tt/2JPktGI

Ocular Basidiobolomycosis: A Case Report

Background: Ocular basidiobolomycosis is an unusual infection caused by fungus of the order Entomophthorales. This fungus has been previously reported as a common cause of skin, subcutaneous, and gastrointestinal tract infection. The fungus isolation and its typical characteristics are clues for diagnosis of this uncommon pathogen. Case Report: A 47-year-old male patient with nodular scleritis in the left eye after an eye injury from sawdust was treated as bacterial scleritis. The lesion improved with early surgical drainage and antibacterial therapy; then, he was discharged from the hospital. Thereafter, the patient was re-admitted due to progression of infectious scleritis with keratitis and orbital cellulitis. Surgical abscess drainage was performed again. The microbiological study demonstrated Basidiobolus ranarum. The patient was treated with topical ketoconazole, subconjunctival fluconazole injection, and oral itraconazole with partial response to the treatment. However, the patient eventually denied any further treatment and did not return for follow-up. Conclusions: B. ranarum is a rare pathogen of ocular infection in which a definite diagnosis requires isolation of the causative organism. Delay in diagnosis and appropriate treatment can lead to extension of the infection and poor outcomes.
Case Rep Ophthalmol 2018;9:315–321

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Atypical Presentation of IgA Nephropathy Mimicking Acute Pyelonephritis

Background. IgA glomerulonephritis may present with hematuria, flank pain, and fever. This clinical presentation may be easily confused with acute pyelonephritis. Case Report. We present the case of a 25-year-old female with a typical clinical presentation for acute pyelonephritis (high fever, left flank pain, left costovertebral angle tenderness, hematuria, elevated inflammatory markers, and a hypoenhancing region in the left kidney on contrast-enhanced computed tomography). However, urine and blood cultures were both negative, the serum creatinine was elevated, and the urinalysis revealed significant proteinuria and dysmorphic red blood cells. A kidney biopsy confirmed a diagnosis of IgA nephropathy. She was treated with a combination of lisinopril and methylprednisolone, with good response. Conclusion. Gross hematuria, especially in the absence of pyuria or bacteriuria, should raise the suspicion for underlying IgA nephropathy, even if the rest of the clinical presentation is typical for a urinary tract infection. The presence of significant proteinuria, red blood cell casts, and dysmorphic red blood cells are useful clues suggesting glomerular disease.

https://ift.tt/2LMD97r

Gastric inlet obstruction from oesophageal cancer with internalized gastric band: a worrisome outcome?

Abstract

Band erosion is one late complication of laparoscopic adjustable gastric banding (LAGB), with the reported incidence between 1% and 28%. Far less common is oesophageal adenocarcinoma after LAGB, with only three cases previously described. Here we report a single case of complete gastric inlet obstruction with oesophageal adenocarcinoma and complete internalization of a gastric band 19 years after its placement.

https://ift.tt/2y9XiSY

Enlargement of papillary glioneuronal tumor in an adult after a follow-up period of 10 years: a case report

Abstract

Papillary glioneuronal tumor (PGNT) is a rare brain tumor grouped under mixed glioneuronal tumors according to the World Health Organization Classification of the Central Nervous System. The natural history of this pathology is not yet well documented. We report a case of PGNT that increased in size after a follow-up period of 10 years. An enlarged cyst wall and nodule showed a low intensity signal on T2*-weighted, suggesting hemorrhage during the clinical course. Characteristic pathological findings along with absence of BRAF^V600E mutation identified the tumor as PGNT. The tumor characteristics of PGNT are discussed based on the presented case, with reference to the existing literature.

https://ift.tt/2JCrgEF

Extracorporeal cardiopulmonary resuscitation in a neonate after air embolism during insufflation for laparoscopic peritoneal dialysis catheter placement

Abstract

Laparoscopy is increasingly utilized in neonatal surgery with safe and effective outcomes. Air embolism from insufflation for pneumoperitoneum is a rare but known risk of laparoscopy. Here we present a rare case of air embolism during insufflation for laparoscopic peritoneal dialysis catheter placement treated with extracorporeal cardiopulmonary resuscitation.

https://ift.tt/2JFJRvm

Perforation of a mesenteric Meckel’s diverticulum

Abstract

Meckel's diverticulum is a remnant of the embryologic omphalomeseteric duct and is a common congenital anomaly found in ~2% of the population. The clinical significance of this anomaly is that the persistent diverticulum can lead to intestinal obstruction or diverticulitis and may contain ectopic tissue which can lead to bleeding, ulceration or perforation. The classic location of a Meckel's diverticulum has been described ~40 cm from the ileocecal valve on the antimesenteric side of the distal ileum. There have only been a few documented cases of a Meckel's diverticulum found on the mesenteric border of the ileum. In this report, we describe a patient who presented with a perforated Meckel's diverticulum which was found on the mesenteric border and performed a review to determine the significance of this finding.

https://ift.tt/2JzcxdB

Surgical management of iatrogenic left main coronary artery dissection

Abstract

This is the case of a 40-year-old female diagnosed with NSTEMI. She underwent coronary angiography and suffered from type F left main coronary artery dissection. After hemodynamic stabilization, she was transferred to the nearest cardiothoracic surgery unit and underwent emergency coronary artery bypass graft (CABG) surgery. This report highlights important concepts in the management of a rare complication and emphasizes the surgical treatment decision-making, underlying an unusual but effective treatment approach.

https://ift.tt/2y70I8S

Delayed central nervous system manifestation of Chikungunya virus with magnetic resonance T2 weighted imaging high signal changes—a case report

Abstract

CHIKV is a relatively new virus and we are still learning about the illness. Very little is known about CNS its involvement and even less about its delayed or long-term manifestations if any. It therefore behoves us to consider delayed CNS involvement when assessing patients with CHIKV infections that may not have had an acute neurological manifestation at the time of diagnosis coupled with new onset neurological manifestations and MRI abnormalities. It seems likely that patients with CHIKV may experience delayed CNS manifestation of the viral infection. This report highlights the importance of a travel history when assessing patients with a neurological complaint. The pathway to best manage such cases is with repeated imaging to assess if the signal changes either progress, resolve or more importantly if there is any MRI correlation should changes in neurology develop during the surveillance period.

https://ift.tt/2Mpk2BF

Stenotrophomonas maltophilia Meningitis in a Term Healthy Neonate: A Case Report and Literature Review

Stenotrophomonas maltophilia is an environmental bacterium of growing concern due to its multidrug resistance and pathogenic potential. It is considered an opportunistic pathogen of nosocomial origin most of the time, targeting a specific patients' population. We describe a case of a previously healthy full-term neonate who was found to have S. maltophilia meningitis and was successfully treated with a combination of Trimethoprim-Sulfamethoxazole and Ciprofloxacin.

https://ift.tt/2ygRR4T

Diagnostic accuracy of inferior vena caval respiratory variation in detecting fluid unresponsiveness: A systematic review and meta-analysis

BACKGROUND The accuracy of respiratory variation of the inferior vena cava (rvIVC) in predicting fluid responsiveness, particularly in spontaneously breathing patients is unclear. OBJECTIVES To consider the evidence to support the accuracy of rvIVC in identifying patients who are unlikely to benefit from fluid administration. DESIGN Systematic review and meta-analysis. DATA SOURCE We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILCAS and WHO Clinical Trial Registry from inception to June 2017. ELIGIBILITY CRITERIA Case–control or cohort studies that evaluated the accuracy of rvIVC in living adult humans were included. A study was included in the meta-analysis if data enabling construction of 2 × 2 tables were reported, calculated or could be obtained from authors and met the above cited criteria. RESULT A total of 23 studies including 1574 patients were included in qualitative analysis. The meta-analysis involved 20 studies and 761 patients. Pooled sensitivity and specificity of rvIVC in 330 spontaneously breathing patients were 0.80 [95% confidence interval (CI) 0.68 to 0.89] and 0.79 (95% CI 0.60 to 0.90). Pooled sensitivity and specificity of rvIVC in 431 mechanically ventilated patients were 0.79 (95% CI 0.67 to 0.86) and 0.70 (95% CI 0.63 to 0.76). CONCLUSION Decreased inferior vena caval respiratory variation is moderately accurate in predicting fluid unresponsiveness both in spontaneous and mechanically ventilated patients. The findings of this review should be used in the appropriate clinical context and in conjunction with other clinical assessments of fluid status. IDENTIFIER CRD 42017068028. Correspondence to Dr Saurabh K. Das, Department of Critical Care, Artemis Hospital, Gurgaram, Haryana, India E-mail: drsauravdas1977@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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Expression and functional characterization of FOXM1 in non-small cell lung cancer

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Sirtuin-4 (SIRT4), a therapeutic target with oncogenic and tumor-suppressive activity in cancer

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