Σάββατο 7 Απριλίου 2018

Glioblastoma Metastatic to the Ovary, a Very Different Krukenberg Tumor?

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Publication date: Available online 7 April 2018
Source:Practical Radiation Oncology
Author(s): Robin E. Bonomi, Josh Kovoor, Mark Zaki, Mark Szlaczky, Michael Christensen, William Kupsky, Geoffrey Barger, Steven Miller, Michael M. Dominello




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Glioblastoma Metastatic to the Ovary, a Very Different Krukenberg Tumor?

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Publication date: Available online 7 April 2018
Source:Practical Radiation Oncology
Author(s): Robin E. Bonomi, Josh Kovoor, Mark Zaki, Mark Szlaczky, Michael Christensen, William Kupsky, Geoffrey Barger, Steven Miller, Michael M. Dominello




https://ift.tt/2Hiswbg

Investigational agents to enhance the efficacy of chemotherapy or radiation in pancreatic cancer

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Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Myrna Hurtado, Umesh T. Sankpal, Amalendu Ranjan, Rajasekhar Maram, Jamboor K. Vishwanatha, Ganji Purnachandra Nagaraju, Bassel F. El-Rayes, Riyaz Basha
Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays. Cur has a low level of toxicity and promising anti-cancer activity, however, its clinical development has been limited by low bioavailability. Cur analogs and nanoparticles were synthesized to improve Cur's efficacy and bioavailability. These compounds were found to be effective in enhancing the therapeutic effects of chemotherapy in pre-clinical models. Small molecules such as NSAIDs have also been tested for the anti-cancer activity and induction of response of chemotherapy and radiation. Interest in TA, a NSAID, has recently increased due to promising preclinical data demonstrating its anti-cancer properties with minimum toxicity. TA also synergistically increased the response of XRT in PC cells and in an orthotropic mouse model. With strong preclinical evidence, research aimed at developing less toxic therapies for PC using Cur analogues or TA is ready for translation into clinical testing.



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The role of heme iron molecules derived from red and processed meat in the pathogenesis of colorectal carcinoma

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Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): S.M.K. Gamage, Lakal Dissabandara, Alfred King-Yin Lam, Vinod Gopalan
Emerging evidence that heme iron in red meat is a risk factor for colorectal carcinogenesis is a topic that has received recent scrutiny. This review aims to summarise the mechanism of colorectal carcinogenesis by heme contained in red and processed meat. Heme iron can induce cytotoxicity by 'cytotoxic heme factor' and promote surface epithelial cell apoptosis and compensatory epithelial hyperplasia. Heme, induces peroxidation of lipids, leading to free radical formation and generation of DNA adducts in colorectal epithelial cells. In addition, heme catalyses the formation of N-nitroso-compounds, which in turn results in the initiation of colorectal carcinogenesis. Emerging data suggest that intestinal dysbiosis can promote carcinogenic properties of heme. Heme induces multiple genetic alterations by regulating WNT signalling pathway and causing mutations in major colon cancer genes such as APC, TP53 and KRAS. However, a balanced diet containing green vegetables, olive oil and calcium may reduce the carcinogenic effects of heme.



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Radiological Evaluation of Response to Immunotherapy in Brain Tumors: Where Are We Now and Where Are We Going?

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Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Michele Porcu, Cinzia Solinas, Paolo Garofalo, Evandro de Azambuja, Mario Scartozzi, Karen Willard-Gallo, Matthias Preusser, Luca Saba




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The identification and isolation of CTCs: a Biological Rubik’s Cube

Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Cristina Mansilla, Elena Soria, Natalia Ramírez
Liquid biopsy represents an alternative to conventional biopsies for the evaluation of tumors mainly due to its easy sampling. One of the main applications is the enumeration of Circulating Tumor Cells (CTCs) to evaluate tumor progression or response to treatment. The analysis of the functional characteristics of CTCs could give us much more information about their role in order to establish a more personalized treatment for the patients. The major issue that has to be solved is the isolation of the CTC population. Multiple protocols have been developed, however none of them has demonstrated to be the definitive one. In fact, a combination of these techniques has often been performed in order to obtain a purer and viable population of CTCs. In this review we have summarized for the first time the different combinatorial approaches used in the last years to optimize the isolation of CTCs and their limitations.



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Investigational agents to enhance the efficacy of chemotherapy or radiation in pancreatic cancer

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Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Myrna Hurtado, Umesh T. Sankpal, Amalendu Ranjan, Rajasekhar Maram, Jamboor K. Vishwanatha, Ganji Purnachandra Nagaraju, Bassel F. El-Rayes, Riyaz Basha
Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays. Cur has a low level of toxicity and promising anti-cancer activity, however, its clinical development has been limited by low bioavailability. Cur analogs and nanoparticles were synthesized to improve Cur's efficacy and bioavailability. These compounds were found to be effective in enhancing the therapeutic effects of chemotherapy in pre-clinical models. Small molecules such as NSAIDs have also been tested for the anti-cancer activity and induction of response of chemotherapy and radiation. Interest in TA, a NSAID, has recently increased due to promising preclinical data demonstrating its anti-cancer properties with minimum toxicity. TA also synergistically increased the response of XRT in PC cells and in an orthotropic mouse model. With strong preclinical evidence, research aimed at developing less toxic therapies for PC using Cur analogues or TA is ready for translation into clinical testing.



https://ift.tt/2IAy7Ju

The role of heme iron molecules derived from red and processed meat in the pathogenesis of colorectal carcinoma

alertIcon.gif

Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): S.M.K. Gamage, Lakal Dissabandara, Alfred King-Yin Lam, Vinod Gopalan
Emerging evidence that heme iron in red meat is a risk factor for colorectal carcinogenesis is a topic that has received recent scrutiny. This review aims to summarise the mechanism of colorectal carcinogenesis by heme contained in red and processed meat. Heme iron can induce cytotoxicity by 'cytotoxic heme factor' and promote surface epithelial cell apoptosis and compensatory epithelial hyperplasia. Heme, induces peroxidation of lipids, leading to free radical formation and generation of DNA adducts in colorectal epithelial cells. In addition, heme catalyses the formation of N-nitroso-compounds, which in turn results in the initiation of colorectal carcinogenesis. Emerging data suggest that intestinal dysbiosis can promote carcinogenic properties of heme. Heme induces multiple genetic alterations by regulating WNT signalling pathway and causing mutations in major colon cancer genes such as APC, TP53 and KRAS. However, a balanced diet containing green vegetables, olive oil and calcium may reduce the carcinogenic effects of heme.



https://ift.tt/2qbf162

Radiological Evaluation of Response to Immunotherapy in Brain Tumors: Where Are We Now and Where Are We Going?

alertIcon.gif

Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Michele Porcu, Cinzia Solinas, Paolo Garofalo, Evandro de Azambuja, Mario Scartozzi, Karen Willard-Gallo, Matthias Preusser, Luca Saba




https://ift.tt/2IAy5Bm

The identification and isolation of CTCs: a Biological Rubik’s Cube

Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Cristina Mansilla, Elena Soria, Natalia Ramírez
Liquid biopsy represents an alternative to conventional biopsies for the evaluation of tumors mainly due to its easy sampling. One of the main applications is the enumeration of Circulating Tumor Cells (CTCs) to evaluate tumor progression or response to treatment. The analysis of the functional characteristics of CTCs could give us much more information about their role in order to establish a more personalized treatment for the patients. The major issue that has to be solved is the isolation of the CTC population. Multiple protocols have been developed, however none of them has demonstrated to be the definitive one. In fact, a combination of these techniques has often been performed in order to obtain a purer and viable population of CTCs. In this review we have summarized for the first time the different combinatorial approaches used in the last years to optimize the isolation of CTCs and their limitations.



https://ift.tt/2qd12ga

Early Response Assessment on Mid-Treatment CT Predicts Loco-Regional Recurrence in Oropharyngeal Cancer Patients Treated with Definitive Radiation Therapy

Publication date: Available online 6 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rafi Kabarriti, N. Patrik Brodin, George Lundgren, Nitin Ohri, Wolfgang A. Tomé, Shalom Kalnicki, Madhur K. Garg
Purpose/Objective(s)To evaluate if response assessment based on mid-treatment computed tomography (CT) scans during definitive radiation therapy (RT) for oropharyngeal head and neck cancer (HNC) can predict for loco-regional recurrence (LRR).Materials/MethodsHNC patients treated at our institution with RT undergo CT rescans at 15th fraction and are replanned in case of inadequate dose to gross disease or increased dose to organs-at-risk. A retrospective cohort analysis was performed on 96 consecutive patients with oropharyngeal cancer treated in 2007-2015 with mid-treatment rescans. The volume of primary disease and involved lymph nodes were delineated on pre- and mid-treatment CT. Univariable and multivariable Cox proportional hazards regression analysis were used to evaluate the efficacy of mid-treatment reduction in tumor volume as a predictor of LRR. Risk-stratification was performed by dichotomizing patients into high- and low-risk groups based on mid-treatment response as well as p-16 status and smoking history.ResultsWith a median follow-up of 34 months, 14 patients experienced LRR. The median reduction in total tumor volume was 18.7% (IQR: 8.4%-30.9%). Reduction in total tumor volume > median is an independent predictor of LRR (HR: 0.22; 95%CI: 0.05–0.89; p=0.020), and the reduction in primary tumor volume is an even stronger predictor (HR: 0.11; 95%CI: 0.02–0.57; p=0.002). Stratifying patients into a high-risk group with reduction in total tumor volume at mid-treatment ≤ median, p-16 negative status, and smoking status >10 pack years, and a low-risk group without these factors, there was a clear separation in Kaplan-Meier curves with actuarial 3-year loco-regional control, progression-free survival and overall survival rates for the high-risk patients of 45.7%, 38.2%, 71.8% compared to 90.7%, 70.6%, 89.8% for low-risk patients, respectively (p≤0.021 for all).ConclusionOur study shows that early response assessment based on mid-treatment CT is an independent predictor of LRR and can be used to effectively distinguish high-risk and low-risk patients, allowing for risk-adaptive treatment stratification at the midway point.

Teaser

In a cohort study of 96 oropharyngeal cancer patients undergoing definitive radiation therapy, we identified early response assessment based on mid-treatment CT at the 15th RT fraction as an independent predictor of locoregional recurrence. Combining this with p-16 and smoking status, we were able to effectively distinguish high-risk and low-risk patients, potentially allowing for more precise risk-adaptive treatment stratification.


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Early Response Assessment on Mid-Treatment CT Predicts Loco-Regional Recurrence in Oropharyngeal Cancer Patients Treated with Definitive Radiation Therapy

Publication date: Available online 6 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rafi Kabarriti, N. Patrik Brodin, George Lundgren, Nitin Ohri, Wolfgang A. Tomé, Shalom Kalnicki, Madhur K. Garg
Purpose/Objective(s)To evaluate if response assessment based on mid-treatment computed tomography (CT) scans during definitive radiation therapy (RT) for oropharyngeal head and neck cancer (HNC) can predict for loco-regional recurrence (LRR).Materials/MethodsHNC patients treated at our institution with RT undergo CT rescans at 15th fraction and are replanned in case of inadequate dose to gross disease or increased dose to organs-at-risk. A retrospective cohort analysis was performed on 96 consecutive patients with oropharyngeal cancer treated in 2007-2015 with mid-treatment rescans. The volume of primary disease and involved lymph nodes were delineated on pre- and mid-treatment CT. Univariable and multivariable Cox proportional hazards regression analysis were used to evaluate the efficacy of mid-treatment reduction in tumor volume as a predictor of LRR. Risk-stratification was performed by dichotomizing patients into high- and low-risk groups based on mid-treatment response as well as p-16 status and smoking history.ResultsWith a median follow-up of 34 months, 14 patients experienced LRR. The median reduction in total tumor volume was 18.7% (IQR: 8.4%-30.9%). Reduction in total tumor volume > median is an independent predictor of LRR (HR: 0.22; 95%CI: 0.05–0.89; p=0.020), and the reduction in primary tumor volume is an even stronger predictor (HR: 0.11; 95%CI: 0.02–0.57; p=0.002). Stratifying patients into a high-risk group with reduction in total tumor volume at mid-treatment ≤ median, p-16 negative status, and smoking status >10 pack years, and a low-risk group without these factors, there was a clear separation in Kaplan-Meier curves with actuarial 3-year loco-regional control, progression-free survival and overall survival rates for the high-risk patients of 45.7%, 38.2%, 71.8% compared to 90.7%, 70.6%, 89.8% for low-risk patients, respectively (p≤0.021 for all).ConclusionOur study shows that early response assessment based on mid-treatment CT is an independent predictor of LRR and can be used to effectively distinguish high-risk and low-risk patients, allowing for risk-adaptive treatment stratification at the midway point.

Teaser

In a cohort study of 96 oropharyngeal cancer patients undergoing definitive radiation therapy, we identified early response assessment based on mid-treatment CT at the 15th RT fraction as an independent predictor of locoregional recurrence. Combining this with p-16 and smoking status, we were able to effectively distinguish high-risk and low-risk patients, potentially allowing for more precise risk-adaptive treatment stratification.


https://ift.tt/2GIQM5g

Bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young male patient following MDMA intake

MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is an illicit drug frequently used by young people at parties and 'raves'. It is readily available in spite of the fact that it is illegal.1 It is perceived by a lot of young people as being 'harmless', but there have been a few high-profile deaths associated with its use.2 Known side effects of MDMA include hyperthermia, rhabdomyolysis, coagulopathy and cardiac arrhythmias.3 Rarer side effects include surgical emphysema and pneumomediastinum, which have been better described with cocaine abuse.4–6 We present a case of bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young man after taking ecstasy.



https://ift.tt/2Esatwc

Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Fetuses exposed to warfarin during pregnancy are at an increased risk of developing an embryopathy known as fetal warfarin syndrome or warfarin embryopathy. The most consistent anomalies are nasal hypoplasia and stippling of vertebrae or bony epiphyses. Management of pregnant patients on anticoagulation is challenging. Current guidelines suggest the use of warfarin if the therapeutic dose is ≤5 mg/day. We report the case of a newborn with signs of warfarin embryopathy born from a mother anticoagulated with warfarin due to mechanical mitral and aortic heart valves. Warfarin was required at the dose of 5 mg/day and was withheld without medical advice between weeks 8 and 10 with no other anticoagulation. The newborn presented with skeletal abnormalities and a ventricular septal defect that have not required specific treatment during the first year of life. Low-dose warfarin is associated with a lower risk of warfarin-related fetopathy but the risk of embryopathy seems unchanged.



https://ift.tt/2Hfvg9l

Pemphigoid gestationis successfully treated with intravenous immunoglobulin

Pemphigoid gestationis (PG), also known as herpes gestationis, is a rare autoimmune blistering disease specific to pregnancy, which usually presents in the second or third trimesters and, in 15%–25% of cases, during the immediate postpartum period.1Although the ethiopathogeny of PG is not fully clarified, most patients develop antibodies against a 180 kDa transmembrane hemidesmosomal protein (BP180; BPAG2; collagen XVII).2 PG has a strong association with human leucocyte antigens DR3 and DR4.3

We report a case of a 29-year-old female patient with PG successfully treated with intravenous immunoglobulin.



https://ift.tt/2GIVUGP

Novel MRI of mediastinal masses: internal differentiation of a thymoma and lymphoma with T1 and T2 mapping

Routine imaging for mediastinal malignancies includes chest X-ray, CT or MRI. T1 and T2 mapping are novel MRI techniques which may have a role in expanding the assessment of internal tumour characteristics. This case report details two middle-aged women who had similar clinical presentations of mediastinal masses of comparable size and appearance when assessed with routine imaging. T1 and T2 maps were acquired on MRI to investigate whether these tumours could be further differentiated prior to surgery. T1 and T2 mapping supported suspicion for which tumour components were solid and cystic, as subsequently confirmed histologically. Furthermore, comparison between the two tumours showed native T1 values differed within the solid components by 37%, correlating to differences in proteinaceous material within the tumour types. This radiological–pathological correlation provides evidence that T1 and T2 mapping has clinical utility in the assessment and differentiation of mediastinal masses.



https://ift.tt/2HkVk3a

Anti-N-methyl-D-aspartate receptor encephalitis relapse in the brainstem

Description

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder involving IgG antibody reaction against NMDAR. It typically develops in women with ovarian teratoma, and its characteristic clinical symptoms include acute behavioural change, psychosis, movement disorder, seizure and autonomic dysfunction. Long-term management in an intensive care unit and immunosuppressive therapy are necessary in most cases, but good prognosis is achieved with appropriate treatment.1 Here, we report a case of anti-NMDAR encephalitis that improved without treatment, but relapsed involving a different brainstem lesion without any symptoms.

A 36-year-old woman was admitted with headache and a single partial seizure 2 weeks after influenza-like fever. At admission, her physical and neurological examination findings as well as routine blood examination results were normal. Cerebrospinal fluid (CSF) analysis revealed a cell count of 163/μL (neutrophil-to-lymphocyte ratio, 15:1) and protein level of 47 mg/dL. MRI showed slight swelling in the limbic system. Meningitis was suspected;...



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Double venous compression due to duplicated inferior vena cava-induced right common iliac vein thrombosis

Venous compression syndromes are caused by extrinsic venous compression of anatomical structures, such as the adjacent arteries and bones. Chronic venous compression and pulsative vibratory arterial pressure accelerate the development of deep vein thrombosis. Herein, we report the first case of double venous compressions due to a duplicated inferior vena cava-induced right-sided common iliac vein thrombosis. The thrombus was induced by left-sided inferior vena cava entrapment and right-sided common iliac vein compression, resembling nutcracker syndrome and May-Thurner syndrome, respectively. Bypass flow of the right inferior vena cava rendered the right lower extremity asymptomatic. Once daily anticoagulation edoxaban was effective. Congenital venous anomalies and bypass formations should be considered when a common iliac vein thrombus without symptoms in the lower extremities is observed, and a lifelong periodical follow-up is mandatory, even after remission.



https://ift.tt/2HiMPFu

Good clinical history scores over extensive workup in unmasking a case of galactorrhoea

The clinical presentation of a young woman with galactorrhoea is described in detail including the history and clinical examination findings. While the patient and her family members feared a serious medical condition which had so far been an obscurity despite a number of investigations, we tried to diagnose the patient starting from the basics, which after a proper history revealed a levosulpiride-induced galactorrhoea. This again lays emphasis on the old adage in medical field that 'a proper history and examination are the key to diagnosis'. There are few reports pertaining to levosulpiride-induced galactorrhoea making it a rare side effect of this drug. We further try to discuss the different causes of galactorrhoea in a young non-pregnant woman which can be encountered in clinical practice.



https://ift.tt/2GIFKwU

Acute lower limb ischaemia secondary to intestinal occlusion

In general, acute lower limb ischaemia is caused by embolic, thrombotic or traumatic phenomena. Here, we describe the case of a 67-year-old woman in an emergency room setting who was initially assessed for paralysis and numbness of her lower left limb. On physical examination, the abdomen was distended and non-compressible. An abdominal AngioScan showed complete occlusion of the left iliac artery by extrinsic compression of the dilated small intestine. After a review of the literature, no case was found describing a lower limb ischaemia by extrinsic vascular compression secondary to a compartment syndrome caused by small bowel obstruction. The treatment of this case required surgical decompression of the abdomen which led to an instantaneous reperfusion of the left leg. Unfortunately, the patient deceased a few hours after the surgery due to haemodynamic deterioration.



https://ift.tt/2HhJKFI

Atypical mycobacteriosis in a poorly compliant patient

Description

Non-tuberculous mycobacteriosis most frequently presents as chronic lung disease.1 Delayed diagnosis or even misdiagnosis occurs due to a great similarity in its clinical presentation to tuberculosis.2 Treatment often seems unprofitable since it is complex and prolonged, poorly tolerated and frequently ineffective in the elimination of the disease.3

The authors present a 68-year-old woman with a history of pulmonary tuberculosis 1 year before, for which she only completed 6 weeks of treatment as well as follow-up, having abandoned both as she believed they went against her culture and religion. She was admitted with productive cough, weakness and weight loss. Blood tests revealed anaemia, thrombocytosis, elevated inflammatory markers, severe hypoalbuminaemia and negative HIV serology. The chest X-ray (figure 1) showed two cavities in the right lung and a consolidation in the left lower lobe. The chest CT scan (figures 2 and 3



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Acute mucocutaneous methotrexate toxicity with marked tissue eosinophilia

Methotrexate toxicity in mucocutaneous areas is usually not associated with tissue eosinophilia. We describe a case of acute methotrexate-induced mucocutaneous erosions with interface dermatitis and eosinophils. A 76-year-old African-American woman with a history of bullous pemphigoid on methotrexate therapy presented with lower extremity cellulitis, developing oral and cutaneous erosions during hospitalization after daily dosage of methotrexate. Shallow circular cutaneous erosions were found on chest, abdomen and limbs. Laboratory results showed pancytopaenia and elevated liver function tests. Skin biopsy revealed irregular acanthotic epidermis with interface dermatitis, individual dyskeratotic cells and superficial perivascular lymphocytic infiltrate with numerous eosinophils. Methotrexate was stopped and leucovorin was administered, leading to improvement. The histopathological changes in acute mucocutaneous toxicity range from pauci-inflammatory erosions with dyskeratotic keratinocytes to interface dermatitis and infrequently seen eosinophils. This case exemplifies that interface dermatitis with a marked eosinophilic infiltrate can be found in the setting of acute mucocutaneous methotrexate toxicity.



https://ift.tt/2Hfh4x6

Spatiotemporal heterogeneity and patterning of developing renal blood vessels

Abstract

The kidney vasculature facilitates the excretion of wastes, the dissemination of hormones, and the regulation of blood chemistry. To carry out these diverse functions, the vasculature is regionalized within the kidney and along the nephron. However, when and how endothelial regionalization occurs remains unknown. Here, we examine the developing kidney vasculature to assess its 3-dimensional structure and transcriptional heterogeneity. First, we observe that endothelial cells (ECs) grow coordinately with the kidney bud as early as E10.5, and begin to show signs of specification by E13.5 when the first arteries can be identified. We then focus on how ECs pattern and remodel with respect to the developing nephron and collecting duct epithelia. ECs circumscribe nephron progenitor populations at the distal tips of the ureteric bud (UB) tree and form stereotyped cruciform structures around each tip. Beginning at the renal vesicle (RV) stage, ECs form a continuous plexus around developing nephrons. The endothelial plexus envelops and elaborates with the maturing nephron, becoming preferentially enriched along the early distal tubule. Lastly, we perform transcriptional and immunofluorescent screens to characterize spatiotemporal heterogeneity in the kidney vasculature and identify novel regionally enriched genes. A better understanding of development of the kidney vasculature will help instruct engineering of properly vascularized ex vivo kidneys and evaluate diseased kidneys.



https://ift.tt/2qescSL

Spatiotemporal heterogeneity and patterning of developing renal blood vessels

Abstract

The kidney vasculature facilitates the excretion of wastes, the dissemination of hormones, and the regulation of blood chemistry. To carry out these diverse functions, the vasculature is regionalized within the kidney and along the nephron. However, when and how endothelial regionalization occurs remains unknown. Here, we examine the developing kidney vasculature to assess its 3-dimensional structure and transcriptional heterogeneity. First, we observe that endothelial cells (ECs) grow coordinately with the kidney bud as early as E10.5, and begin to show signs of specification by E13.5 when the first arteries can be identified. We then focus on how ECs pattern and remodel with respect to the developing nephron and collecting duct epithelia. ECs circumscribe nephron progenitor populations at the distal tips of the ureteric bud (UB) tree and form stereotyped cruciform structures around each tip. Beginning at the renal vesicle (RV) stage, ECs form a continuous plexus around developing nephrons. The endothelial plexus envelops and elaborates with the maturing nephron, becoming preferentially enriched along the early distal tubule. Lastly, we perform transcriptional and immunofluorescent screens to characterize spatiotemporal heterogeneity in the kidney vasculature and identify novel regionally enriched genes. A better understanding of development of the kidney vasculature will help instruct engineering of properly vascularized ex vivo kidneys and evaluate diseased kidneys.



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Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers doi: 10.3390/cancers10040111

Authors: Valentina Ovalle Eric A. Strom Simona Shaitelman Karen Hoffman Richard Amos George Perkins Welela Tereffe Benjamin D. Smith Michael Stauder Wendy Woodward

Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume (CTV) was treated with two or three passively-scattered proton beams to a dose of 34 Gy in 10 fractions in one week. Photographs were taken at the end of radiation, at two weeks, six weeks, and every six months thereafter. Mammography was obtained at six months after radiation and annually thereafter. All visual changes were categorized using the smallest meaningful gradations in findings and are demonstrated herein. All treatment-related mammographic findings are reported. Findings: Visual and mammographic findings showed a clear time-dependent relationship and significant variation between individuals. Peak skin reaction occurred at two to six weeks after completion of therapy. At two weeks most patients had either no visible effects and patchy erythema involving <50% of the treated skin (60%). At six weeks most patients had either patchy erythema involving <50% of the overlying skin (33%) or patchy erythema involving >50% of the treated skin (28%). Only one patient developed any moist desquamation. At six months most patients had no visible skin changes (57%) or a small, circular area of mild hyperpigmentation (33%). Mammographic changes seen at six months were regional skin thickening (40%), residual seroma (14%), localized retraction (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was developed to foster granular recording of these findings.



https://ift.tt/2JrMFfV

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers doi: 10.3390/cancers10040111

Authors: Valentina Ovalle Eric A. Strom Simona Shaitelman Karen Hoffman Richard Amos George Perkins Welela Tereffe Benjamin D. Smith Michael Stauder Wendy Woodward

Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume (CTV) was treated with two or three passively-scattered proton beams to a dose of 34 Gy in 10 fractions in one week. Photographs were taken at the end of radiation, at two weeks, six weeks, and every six months thereafter. Mammography was obtained at six months after radiation and annually thereafter. All visual changes were categorized using the smallest meaningful gradations in findings and are demonstrated herein. All treatment-related mammographic findings are reported. Findings: Visual and mammographic findings showed a clear time-dependent relationship and significant variation between individuals. Peak skin reaction occurred at two to six weeks after completion of therapy. At two weeks most patients had either no visible effects and patchy erythema involving <50% of the treated skin (60%). At six weeks most patients had either patchy erythema involving <50% of the overlying skin (33%) or patchy erythema involving >50% of the treated skin (28%). Only one patient developed any moist desquamation. At six months most patients had no visible skin changes (57%) or a small, circular area of mild hyperpigmentation (33%). Mammographic changes seen at six months were regional skin thickening (40%), residual seroma (14%), localized retraction (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was developed to foster granular recording of these findings.



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Sarcomatoid Adenocarcinoma of the Ampulla of Vater

Abstract

Sarcomatoid adenocarcinoma of ampulla of Vater is an extremely rare malignant neoplasm that displays both carcinomatous and sarcomatous component. A 58-year-old woman was admitted to our hospital under the suspicion of an ampulla of Vater cancer. Abdominal computed tomography and endoscopy demonstrated a bulging of ampulla and the biopsy specimen revealed an adenocarcinoma, well differentiated in the background of tubulovillous adenoma. So we performed the pylorus preserving pancreaticoduodenectomy. At postoperative biopsy, the tumor was composed of adenocarcinoma component and sarcomatoid component. Thus, a diagnosis of sarcomatoid adenocarcinoma of ampulla of Vater could be made. Here, we present a case of sarcomatoid adenocarcinoma of ampulla of Vater.



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Sarcomatoid Adenocarcinoma of the Ampulla of Vater

Abstract

Sarcomatoid adenocarcinoma of ampulla of Vater is an extremely rare malignant neoplasm that displays both carcinomatous and sarcomatous component. A 58-year-old woman was admitted to our hospital under the suspicion of an ampulla of Vater cancer. Abdominal computed tomography and endoscopy demonstrated a bulging of ampulla and the biopsy specimen revealed an adenocarcinoma, well differentiated in the background of tubulovillous adenoma. So we performed the pylorus preserving pancreaticoduodenectomy. At postoperative biopsy, the tumor was composed of adenocarcinoma component and sarcomatoid component. Thus, a diagnosis of sarcomatoid adenocarcinoma of ampulla of Vater could be made. Here, we present a case of sarcomatoid adenocarcinoma of ampulla of Vater.



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Knockdown of fibrous sheath interacting protein 1 expression reduces bladder urothelial carcinoma cell proliferation and induces apoptosis via inhibition of the PI3K/AKT pathway

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miR-495 inhibits proliferation, migration, and invasion and induces apoptosis via inhibiting PBX3 in melanoma cells

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Fabrication of ultrasmall WS2 quantum dots-coated periodic mesoporous organosilica nanoparticles for intracellular drug delivery and synergistic chemo-photothermal therapy

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PET-CT evaluation of the curative effect of crizotinib on malignant myofibroblastoma with rare mutation of ALK R401: a case report and literature review

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Downregulation of miR-542-3p promotes cancer metastasis through activating TGF-β/Smad signaling in hepatocellular carcinoma

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Preferential allelic deletion of RBSP3, LIMD1 and CDC25A in head and neck squamous cell carcinoma: Implication in cancer screening and early detection.

Preferential allelic deletion of RBSP3, LIMD1 and CDC25A in head and neck squamous cell carcinoma: Implication in cancer screening and early detection.

Cancer Biol Ther. 2018 Apr 06;:1-16

Authors: Sarkar S, Panda CK

Abstract
Head and neck squamous cell carcinoma is one of the leading cancers in terms of incidence and mortality. However, no reliable marker till date accurately predicts its progression when altered in healthy tissues. The study aims to identify alleles of microsatellites adjacent to important cell cycle regulatory, tumor suppressor genes altered in early head and neck lesions, viz. RBSP3, LIMD1 and CDC25A, which undergo frequent deletion and can be used for population screening and early detection. DNA for tumors and normal tissues was isolated from 143 patients in different stages of head and neck squamous cell carcinoma. The size of microsatellite present in normal tissues and their deletion in the corresponding tumor was identified, along with the correlation of expression in normal epithelium with respect to allele size. The results revealed a range of alleles (CA9 to CA32) for the different microsatellites of the genes in normal tissues. The larger alleles were significantly deleted with differential deletion of alleles observed in tumors, except for LIMD1, in which the smaller allele was significantly deleted. In normal tissues, some alleles represented as stable alleles with high prevalence, while in tumours, specific sizes showed greater propensity for deletion. However, similar expression of the proteins in normal epithelium adjacent to tumors was observed despite variations in allele size, possibly due to the location of the microsatellites. Thus, those alleles when present in normal tissues and undergoing persistent deletion in tumours could be used as markers for screening and early identification of populations at risk of developing head and neck lesions.

PMID: 29624473 [PubMed - as supplied by publisher]



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Preferential allelic deletion of RBSP3, LIMD1 and CDC25A in head and neck squamous cell carcinoma: Implication in cancer screening and early detection.

Preferential allelic deletion of RBSP3, LIMD1 and CDC25A in head and neck squamous cell carcinoma: Implication in cancer screening and early detection.

Cancer Biol Ther. 2018 Apr 06;:1-16

Authors: Sarkar S, Panda CK

Abstract
Head and neck squamous cell carcinoma is one of the leading cancers in terms of incidence and mortality. However, no reliable marker till date accurately predicts its progression when altered in healthy tissues. The study aims to identify alleles of microsatellites adjacent to important cell cycle regulatory, tumor suppressor genes altered in early head and neck lesions, viz. RBSP3, LIMD1 and CDC25A, which undergo frequent deletion and can be used for population screening and early detection. DNA for tumors and normal tissues was isolated from 143 patients in different stages of head and neck squamous cell carcinoma. The size of microsatellite present in normal tissues and their deletion in the corresponding tumor was identified, along with the correlation of expression in normal epithelium with respect to allele size. The results revealed a range of alleles (CA9 to CA32) for the different microsatellites of the genes in normal tissues. The larger alleles were significantly deleted with differential deletion of alleles observed in tumors, except for LIMD1, in which the smaller allele was significantly deleted. In normal tissues, some alleles represented as stable alleles with high prevalence, while in tumours, specific sizes showed greater propensity for deletion. However, similar expression of the proteins in normal epithelium adjacent to tumors was observed despite variations in allele size, possibly due to the location of the microsatellites. Thus, those alleles when present in normal tissues and undergoing persistent deletion in tumours could be used as markers for screening and early identification of populations at risk of developing head and neck lesions.

PMID: 29624473 [PubMed - as supplied by publisher]



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Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers doi: 10.3390/cancers10040110

Authors: Adrián Montaño Maribel Forero-Castro Darnel Marchena-Mendoza Rocío Benito Jesús María Hernández-Rivas

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.



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Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers doi: 10.3390/cancers10040110

Authors: Adrián Montaño Maribel Forero-Castro Darnel Marchena-Mendoza Rocío Benito Jesús María Hernández-Rivas

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.



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Inhibition of NIPBL enhances the chemosensitivity of non-small-cell lung cancer cells via the DNA damage response and autophagy pathway

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Prognostic value of platelet-to-lymphocyte ratio in pancreatic cancer: a comprehensive meta-analysis of 17 cohort studies

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Postmastectomy radiotherapy reduces locoregional and disease recurrence in patients with stage II–III triple-negative breast cancer treated with neoadjuvant chemotherapy and mastectomy

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Comprehensive Acute Pain Management in the Perioperative Surgical Home

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Publication date: Available online 7 April 2018
Source:Anesthesiology Clinics
Author(s): John-Paul J. Pozek, Martin De Ruyter, Talal W. Khan

Teaser

The careful coordination of care throughout the perioperative continuum offered by the perioperative surgical home (PSH) is important in the treatment of postoperative pain. Physician anesthesiologists have expertise in acute pain management, pharmacology, and regional and neuraxial anesthetic techniques, making them ideal leaders for managing perioperative analgesia within the PSH. Severe postoperative pain is one of many patient- and surgery-specific factors in the development of chronic postsurgical pain. Delivering adequate perioperative analgesia is important to avoid this development, to decrease perioperative morbidity, and to improve patient satisfaction.


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Quality and the Health System

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Publication date: Available online 7 April 2018
Source:Anesthesiology Clinics
Author(s): Monaliza Gaw, Frank Rosina, Thomas Diller

Teaser

Since the publication of "To Err is Human" in 1999, substantial efforts have been made within the health care industry to improve quality and patient safety. Although improvements have been made, recent estimates continue to indicate the need for a marked change in approach. In this article, the authors discuss the concepts and characteristics of high reliability organizations, safety culture, and clinical microsystems. The health care delivery system must move beyond current quality and patient safety approaches and fully engage in these new concepts to transform health care system performance.


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Rational design and identification of immuno-oncology drug combinations

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Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Marco A.J. Iafolla, Heather Selby, Kathrin Warner, Pamela S. Ohashi, Benjamin Haibe-Kains, Lillian L. Siu
BackgroundClinical trials investigating immuno-oncology (IO) drug combinations are largely based on empiricism or limited non-clinical evaluations. This study identified the current combination IO drug clinical trials and investigated how tumour molecular profiling can help rationalise IO drug combinations.MethodsIO targets were identified via PubMed search and expert opinion. IO drugs were compiled by searching the National Cancer Institute Drug Dictionary and pharmaceutical pipelines, August 2016. Combination IO trials were obtained by searching doublet IO drug combinations in www.clinicaltrials.gov from September to November 2016. IO target gene expressions were extracted from The Cancer Genome Atlas (TCGA) data set and compared with normal tissues from the Genotype-Tissue Expression database. Differentially expressed genes for each cancer were determined using the Wilcoxon rank-sum test, and p-values were corrected for multiple testing.ResultsIn total, 178 IO targets were identified; 90 targets have either regulatory approved or investigational therapeutics. In total, 410 combination trials involving ≥2 IO drugs were identified: skin (n = 102) and genitourinary (n = 41) malignancies have the largest number of combination IO trials; 109 trials involved >2 disease sites. Summative patient accrual estimates among all trials are 71,345. Trials combining cytotoxic T lymphocyte antigen 4 (CTLA4) with programmed cell death protein 1 (n = 79) and CTLA4 with programmed cell death ligand 1 (n = 44) are the most common. Gene expression data from TCGA were mined to extract the 178 IO targets in 9089 tumours originating from 19 cancer types. IO target expression–clustered heatmap analysis identified several promising drug combinations.ConclusionOur review highlights the great interest in combination IO clinical trials. Our analysis can enrich IO combination therapy selection.



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