Head and Neck Diseases by Alexandros G.Sfakianakis: 10/26/16

Τετάρτη 26 Οκτωβρίου 2016

The head and neck cancer immune landscape and its immunotherapeutic implications.

The head and neck cancer immune landscape and its immunotherapeutic implications.

JCI Insight. 2016 Oct 20;1(17):e89829

Authors: Mandal R, Şenbabaoğlu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N, Lee KW, Ganly I, Hakimi AA, Chan TA, Morris LG

Abstract
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation. We find that both HPV(+) and HPV(-) HNSCC tumors are among the most highly immune-infiltrated cancer types. Strikingly, HNSCC had the highest median Treg/CD8(+) T cell ratio and the highest levels of CD56(dim) NK cell infiltration, in our pan-cancer analysis of the most immune-infiltrated tumors. CD8(+) T cell infiltration and CD56(dim) NK cell infiltration each correlated with superior survival in HNSCC. Tumors harboring genetic smoking signatures had lower immune infiltration and were associated with poorer survival, suggesting these patients may benefit from immune agonist therapy. These findings illuminate the immune landscape of HPV(+) and HPV(-) HNSCC. Additionally, this landscape provides a potentially novel rationale for investigation of agents targeting modulators of Tregs (e.g., CTLA-4, GITR, ICOS, IDO, and VEGFA) and NK cells (e.g., KIR, TIGIT, and 4-1BB) as adjuncts to anti-PD-1 in the treatment of advanced HNSCC.

PMID: 27777979 [PubMed - in process]

http://ift.tt/2dJlHPV

A case of obturator hernia leading to right thigh abscess in China.

A case of obturator hernia leading to right thigh abscess in China.

Int J Surg Case Rep. 2016 Oct 19;28:340-343

Authors: Shen Z, Zhi CY, Wang RN, Gao HC

Abstract
The purpose of this case is to investigate a case of obturator hernia leading to right thigh abscess on 68-year-old woman of China. A 68-year-old Chinese woman was referred to China-Japan Friendship Hospital of Jilin University with abdominal pain, bloating, exhaust, stop defecation in 2011. She had chronic bronchitis, emphysema with a history of 20 years. This patient did not have any bad habits, such as smoking, alcohol consumption, etc. In this surgery, CT was used to diagnose the basic condition of the patient. Surgery was used for treatment of patients with diseases. In addition, this operation was performed by the china-Japan Friendship Hospital of Jilin University. The results of this case showed that the cervix of rectal right anterior wall can hit a funicular neoplasm, toughening, smooth, with tenderness, considering for the external pressure bowel loops. The inside of the right thigh showed obvious swelling, skin slightly bruising, and tenderness. Chest radiographs showed that patients had emphysema, multiple planes of fluid and air in the abdomen. Patients had been successfully operated, but she died because of severe infection.

PMID: 27780090 [PubMed - as supplied by publisher]

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Development of a novel human scFv against EGFR L2 domain by phage display technology.

Development of a novel human scFv against EGFR L2 domain by phage display technology.

Curr Pharm Des. 2016 Sep 28;

Authors: Rahbarnia L, Farajnia S, Babaei H, Majidi J, Veisi K, Khosroshahi SA, Tanomand A

Abstract
Epidermal growth factor receptor (EGFR) as a transmembrane tyrosine kinase receptor is frequently overexpresses in tumors with epithelial origin. The L2 domain from extracellular part of EGFR is involved in ligand binding and the blockage of this domain prevents activation of related signaling pathways. This study was aimed to develop a novel human scFv against EGFR L2 domain as a promising target for cancer therapy. The L2 recombinant protein was purified and used for panning a human scFv phage library (Tomlinson I). In this study a novel screening strategy was applied to select clones with high binding and enrichment of rare specific phage clones of the L2 protein. After the five biopanning rounds several specific clones were isolated which among them one phage clone with high binding was purified for further analysis. The specific interaction of selected clone against target antigen was confirmed by ELISA and western blotting. Immunofluorescence staining showed that purified scFv binds to A431 cells surface displaying EGFR surface receptor. In the present study we isolated for the first time a novel human scFv against EGFR L2 domain. This study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFR overexpressing cancers using this novel human anti-L2 ScFv.

PMID: 27779085 [PubMed - as supplied by publisher]

http://ift.tt/2eKPN85

Successful Treatment of an Unusual Case of FPLD2: The Role of Roux-en-Y Gastric Bypass-Case Report and Literature Review.

Successful Treatment of an Unusual Case of FPLD2: The Role of Roux-en-Y Gastric Bypass-Case Report and Literature Review.

J Gastrointest Surg. 2016 Oct 24;

Authors: Grundfest-Broniatowski S, Yan J, Kroh M, Kilim H, Stephenson A

Abstract
Familial partial lipodystrophy type 2 (FPLD2) is a rare disorder associated with LMNA gene mutations. It is usually marked by loss of subcutaneous fat on the limbs and trunk and severe insulin resistance. Scattered reports have indicated that Roux-en-Y bypass helps to control the diabetes mellitus in these patients. We present here a very unusual patient with FPLD2 who had life-threatening retroperitoneal and renal fat accumulation accompanied by bilateral renal cancers. Following cryotherapy of one renal cancer and a contralateral nephrectomy with debulking of the retroperitoneal fat, Roux-en-Y gastric bypass (RYGB) has successfully controlled the disease for 3 years. The clinical presentations and causes of FPLD are reviewed and the role of RYGB is discussed.

PMID: 27778252 [PubMed - as supplied by publisher]

http://ift.tt/2euoJvo

JAK2 V617F mutation, multiple hematologic and non-hematologic processes: an association?

JAK2 V617F mutation, multiple hematologic and non-hematologic processes: an association?

Biomark Res. 2016;4:19

Authors: Liu KG, Verma A, Derman O, Kornblum N, Janakiram M, Braunschweig I, Battini R

Abstract
BACKGROUND: Population studies showed that patients with JAK2 V617F mutation had increased mortality, and increased risk of any cancer, hematologic cancer, and myeloproliferative disease.
CASE PRESENTATION: A 68-year-old Asian male with JAK2 V617F mutation developed four different hematologic and non-hematologic neoplastic processes. In 2009, he was diagnosed with stage IA lung adenocarcinoma and also noted to have worsening leukocytosis and thrombocytosis with peak platelet count of 1,054,000/mL). Bone marrow biopsy was consistent with myeloproliferative neoplasm. His monocyte percentage increased in 2011 and met criteria for chronic myelomonocytic leukemia. In 2013, he was admitted for proximal small bowel obstruction, with biopsy confirming stage IE diffuse large B-cell lymphoma. In 2014, a bone marrow biopsy performed for worsening leukocytosis was consistent with acute myeloid leukemia with monocytic differentiation.
CONCLUSION: This is a rare case depicting the association of JAK2 V617F mutation with myeloproliferative, lymphoproliferative and solid neoplasms.

PMID: 27777768 [PubMed - in process]

http://ift.tt/2eFrbNa

Giant Cardiac Lipoma: Refined Hypothesis Proposes Invagination from Extracardiac to Intracardiac Sites.

Giant Cardiac Lipoma: Refined Hypothesis Proposes Invagination from Extracardiac to Intracardiac Sites.

Tex Heart Inst J. 2016 Oct;43(5):461-464

Authors: Rainer WG, Bailey DJ, Hollis HW

Abstract
Cardiac lipomas are rare and usually present as benign, encapsulated masses outside the heart; however, they can also be found within the atria. No single theory-including molecular genetic mutation-adequately explains why this occurs. Extensive career experience and broadened knowledge in embryology and cardiac physiology have helped us to develop a hypothesis based on invagination of extracardiac tumors. This report describes a vexing case of a giant right atrial lipoma, from 1985, in which the diagnosis was made incidentally during management of a patient's acute limb ischemia. In addition, we discuss the imaging and treatment of cardiac lipoma.

PMID: 27777537 [PubMed - in process]

http://ift.tt/2eun491

Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review.

Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review.

Br J Gen Pract. 2016 Oct 24;:

Authors: Lim AW, Landy R, Castanon A, Hollingworth A, Hamilton W, Dudding N, Sasieni P

Abstract
BACKGROUND: Cervical cancer in young women presents a diagnostic challenge because gynaecological symptoms are common but underlying disease is rare.
AIM: To explore the potential for using cytology as a diagnostic aid for cervical cancer in young women.
DESIGN AND SETTING: Retrospective review of primary care records and cytology data from the national cervical screening database and national audit of cervical cancers.
METHOD: Four datasets of women aged 20-29 years in England were examined: primary care records and national screening data from an in-depth study of cervical cancers; cytology from the national audit of cervical cancers; whole-population cytology from the national screening database; and general-population primary care records from the Clinical Practice Research Datalink. The authors explored the sensitivity and positive predictive value (PPV) of symptomatic cytology (earliest <12 months before diagnosis) to cervical cancer.
RESULTS: The estimated prevalence of cervical cancer among symptomatic women was between 0.4% and 0.9%. The sensitivity of moderate dyskaryosis (high-grade squamous intraepithelial lesion [HSIL]) or worse in women aged 20-29 years was 90.9% to 96.2% across datasets, regardless of symptom status. The PPV was estimated to be between 10.0% and 30.0%. For women aged 20-24 years, the PPV of '?invasive squamous carcinoma' was 25.4%, and 2.0% for severe or worse cytology.
CONCLUSION: Cytology has value beyond screening, and could be used as a diagnostic aid for earlier detection of cervical cancer in young women with gynaecological symptoms by ruling in urgent referral.

PMID: 27777232 [PubMed - as supplied by publisher]

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Design of a long-term follow-up effectiveness, immunogenicity and safety study of women who received the 9-valent human papillomavirus vaccine.

Design of a long-term follow-up effectiveness, immunogenicity and safety study of women who received the 9-valent human papillomavirus vaccine.

Contemp Clin Trials. 2016 Oct 21;:

Authors: Luxembourg A, Kjaer SK, Nygard M, Ellison MC, Group T, Marshall JB, Radley D, Saah A

Abstract
The 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets four HPV types (6/11/16/18) also covered by the quadrivalent HPV (qHPV) vaccine and five additional types (31/33/45/52/58). Vaccine efficacy to prevent HPV infection and disease was established in a Phase III clinical study in women 16-26years of age. A long-term follow-up (LTFU) study has been initiated as an extension of the Phase III clinical study to assess effectiveness of the 9vHPV vaccine up to at least 14years after the start of vaccination. It includes participants from Denmark, Norway and Sweden and uses national health registries from these countries to assess incidence of cervical pre-cancers and cancers due to the 7 oncogenic types in the vaccine (HPV 16/18/31/33/45/52/58). Incidences will be compared to the estimated incidence rate in an unvaccinated cohort of similar age and risk level. This LTFU study uses a unique design: it is an extension of a Phase III clinical study and also has elements of an epidemiological study (i.e., endpoints based on standard clinical practice; surveillance using searches from health registries); it uses a control chart method to determine whether vaccine effectiveness may be waning. Control chart methods which were developed in industrial and manufacturing settings for process and production monitoring, can be used to monitor disease incidence in real-time and promptly detect a decrease in vaccine effectiveness. Experience from this innovative study design may be applicable to other medicinal products when long-term outcomes need to be assessed, there is no control group, or outcomes are rare.

PMID: 27777126 [PubMed - as supplied by publisher]

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Unusual Adenomatoid Odontogenic Tumor.

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Unusual Adenomatoid Odontogenic Tumor.

J Craniofac Surg. 2016 Mar;27(2):e139-41

Authors: Oliveira MR, Gabrielli MA, Gabrielli MF, Andrade CR, Silva BN, Pereira-Filho VA

Abstract
The adenomatoid odontogenic tumor is a rare benign neoplasm. It can, however, have locally aggressive behavior. This is a case of an adenomatoid odontogenic tumor of unusual location and behavior in a 15-year-old female patient. A panoramic radiograph revealed a large radiolucent lesion involving the retained tooth 33. Teeth involved in this lesion were displaced and with apparent root resorption. A prototype of the mandible showed a marked expansion of cortical bone, fenestration points in the lingual cortex, and fragility of the base of the mandible. Therefore, because of the risk of postoperative pathologic fracture the placement of a 2.4-mm reconstruction plate was indicated. Total enucleation of the lesion, as well as placement of a reconstruction plate were performed. Despite the large bone destruction, with the correct surgical procedure and the use of the reconstruction plate the patient recovered without incidents and a 24-month postoperative radiography showed satisfactory bone formation.

PMID: 26963303 [PubMed - indexed for MEDLINE]

http://ift.tt/2eurNaM

Bilateral Thalamic Glioma: Case Report and Review of the Literature.

Bilateral Thalamic Glioma: Case Report and Review of the Literature.

Turk Neurosurg. 2016;26(2):321-4

Authors: Balasa A, Balasa R, Egyed-Zsigmond I, Chinezu R

Abstract
Bilateral thalamic glioma is extremely rare and the incidence cannot be adequately expressed. We present the case of a 72 years old male suffering from the rapid deterioration of cognitive function to moderately severe dementia in a short period of time. Magnetic resonance studies demonstrated a bilateral thalamic glioma with a minimal focal gadolinium uptake in the left thalamus. Biopsy was performed and pathology report was of anaplastic astrocytoma, WHO grade III. Radiotherapy was proposed but was rejected by the patient's relatives. The patient deceased 57 days later. We performed an extensive review of the literature and by updating the previous described series we can state that to the best of our knowledge this is the 60th case described in the literature and the second eldest patient presented. Patients suffering from this disease present a poor prognosis, the longest survival described being of 3 years in patients diagnosed with grade II bilateral thalamic glioma. Adjuvant therapy in form of radiotherapy to the thalami is most commonly used but the benefits are unclear. The natural progression of WHO grade III bilateral thalamic glioma left untreated, as can be seen from our case, has an even poorer outcome.

PMID: 26956834 [PubMed - indexed for MEDLINE]

http://ift.tt/2eKOq9l

The Coexistence of Rathke Cleft Cyst and Pituitary Adenoma.

The Coexistence of Rathke Cleft Cyst and Pituitary Adenoma.

J Craniofac Surg. 2016 Mar;27(2):e128-30

Authors: Gao M, An Y, Huang Z, Niu J, Yuan X, Bai Y, Guo L

Abstract
Both of Pituitary adenoma (PA) and Rathke cleft cyst (RCC) are the most common and benign sellar lesions. Generally, the origin of RCC is considered to be derived from remnants of Rathke punch, while PA is formed by proliferation of the anterior wall of Rathke pouch. Although they have a possibility to share a common embryological origin, the coexistence of PA and RCC is extremely rare. Here, the authors report a 50-year-old male patient who was found to have a large cystic sellar lesion, and surgical resection revealed components of a RCC coexisting with a PA. This collision reminded us of the possibility of RCC coexisting with PA. Furthermore, a clinicopathologic relation of them were reviewed and investigated.

PMID: 26845092 [PubMed - indexed for MEDLINE]

http://ift.tt/2eKSiY7

Parathyroid cancer - difficult diagnosis - a case report.

Parathyroid cancer - difficult diagnosis - a case report.

Nucl Med Rev Cent East Eur. 2016;19(1):46-50

Authors: Pyzik AJ, Matyjaszek-Matuszek B, Zwolak A, Chrapko B, Pyzik D, Strawa-Zakościelna K

Abstract
Parathyroid cancer is a rare disorder of unclear etiology that is difficult to diagnose and treat. It is most often diagnosed incidentally based on multi-organ non-specific symptoms of hypercalcemia as a consequence of parathyroid hormone oversecretion. We present a case of a male with primary hyperparathyroidism who was diagnosed with parathyroid cancer ectopically located in the mediastinum only after the third surgery. However, due to chronic hypercalcemia, problems with localization and a bad clinical condition, the patient was not able to undergo a radical resection and one year after the first pathological fracture died. Taking into consideration the whole clinical picture we want to emphasize the need to apply comprehensive differential diagnosis of hypercalcemia and localization diagnosis of parathyroid tissue with a use of MIBI scintigraphy accompanied by the computed tomography and magnetic resonance imaging, as the most specific diagnostic tools employed in this pathology.

PMID: 26838944 [PubMed - indexed for MEDLINE]

http://ift.tt/2eukGyY

Non-melanoma skin cancer.

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Non-melanoma skin cancer.

Clin Med (Lond). 2016 Feb;16(1):62-5

Authors: Griffin LL, Ali FR, Lear JT

Abstract
Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy among Caucasians and its incidence continues to rise annually. Exposure to UV radiation initiates approximately 90% of NMSC, causing malignant transformation of keratinocytes and suppression of the inflammatory response. Risk factors include sun exposure and immunosuppression. There are several subtypes of BCC, although histological overlap is common. Surgery has traditionally been regarded as the 'gold-standard' treatment, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (radiotherapy, curettage and cautery, and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC.

PMID: 26833519 [PubMed - indexed for MEDLINE]

http://ift.tt/2eukT5n

Rare gynaecological emergency: massive intraperitoneal haemorrhage from spontaneous rupture of a superficial vessel on a large leiomyoma.

Rare gynaecological emergency: massive intraperitoneal haemorrhage from spontaneous rupture of a superficial vessel on a large leiomyoma.

BMJ Case Rep. 2016 Jan 29;2016:

Authors: Gulati N, Raman S, Srinivasan M, Bakour S

Abstract
Uterine leiomyomas rarely present as gynaecological emergencies. We report a case of a 29-year-old nulliparous woman, with a negative pregnancy test, who presented with collapse and an admission haemoglobin count of 68 g/L. Urgent CT of the abdomen revealed a 14 × 19 × 10 cm uterine fibroid and intraperitoneal free fluid. Emergency laparotomy confirmed massive intraperitoneal haemorrhage from a large serosal vessel on top of a 19 cm subserosal fibroid. A myomectomy was performed, preserving this patient's fertility. Histopathology confirmed a benign leiomyoma with hydropic changes.

PMID: 26825935 [PubMed - indexed for MEDLINE]

http://ift.tt/2eKPH06

Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases.

Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases.

Hepatobiliary Pancreat Dis Int. 2016 Feb;15(1):93-8

Authors: She WH, Chan AC, Cheung TT, Chok KSh, Chan SC, Poon RT, Lo CM

Abstract
BACKGROUND: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma.
METHODS: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications.
RESULTS: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication.
CONCLUSIONS: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

PMID: 26818549 [PubMed - indexed for MEDLINE]

http://ift.tt/2eunbBr

Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound.

Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound.

Hepatobiliary Pancreat Dis Int. 2016 Feb;15(1):48-54

Authors: Dong Y, Zhu Z, Wang WP, Mao F, Ji ZB

Abstract
BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. It is of clinical importance to differentiate HCA from other liver tumors, especially hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound (CEUS) findings.
METHODS: Twenty-six patients (10 males and 16 females; mean age 36.2+/-5.0 years) with 26 histopathologically proven HCAs were retrospectively identified. According to the maximum diameter of HCAs, they were divided into three groups: <30 mm, 30-50 mm, and >50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit (Philips Bothell, WA, USA). For each lesion, a dose of 2.4 mL SonoVue® (Bracco Imaging Spa, Milan, Italy) was injected as a quick bolus into the cubital vein. Lesions' echogenicity, color-Doppler flow imaging and contrast enhancement patterns were recorded.
RESULTS: Grayscale ultrasound revealed that most of HCAs were hypoechoic (73.1%, 19/26). Spotty calcifications were detected in 26.9% (7/26) of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% (12/26) of the HCAs. CEUS showed that 73.1% (19/26) of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% (14/26) showed decreased contrast enhancement in the late phase. There was no significant difference in enhancement patterns among different sizes of HCAs (P>0.05). Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs.
CONCLUSIONS: CEUS combined with grayscale and color-Doppler flow imaging helped to improve preoperative diagnosis of HCAs. The characteristic imaging features of HCAs included: rapid homogeneous enhancement and slow wash-out pattern on CEUS; heterogeneous echogenicity on grayscale ultrasound; and centripetal enhancement with subcapsular tortuous arteries in large HCAs.

PMID: 26818543 [PubMed - indexed for MEDLINE]

http://ift.tt/2eKP2Mq

PET-avid hepatocellular adenomas: incidental findings associated with HNF1-α mutated lesions.

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PET-avid hepatocellular adenomas: incidental findings associated with HNF1-α mutated lesions.

HPB (Oxford). 2016 Jan;18(1):41-8

Authors: Lee SY, Kingham TP, LaGratta MD, Jessurun J, Cherqui D, Jarnagin WR, Kluger MD

Abstract
BACKGROUND: Hepatocellular adenoma (HCA) is the second most common benign liver neoplasm and occurs predominantly in women in their reproductive years. Positron emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) is commonly used in cancer staging, surveillance and evaluation of treatment response. PET-avid HCA are rare and can be falsely interpreted as malignancies.
METHODS: A retrospective review of four institutions' database was performed to identify the PET-avid HCAs with clinico-pathological correlation.
RESULTS: Nine patients with histological proven PET-avid HCA was identified. Eight out of 9 patients were female with a median age at diagnosis of 44 years. All patients' tumors with available histological subtyping (8/8) were HNF1-α mutated and had no inflammatory changes; 6 out the 9 lesions had prominent (>50%) steatotic changes.
CONCLUSION: Hepatocellular adenomas, specifically the HNF1-α subtype, can cause false-positive PET findings when seeking to identify malignancy. Concomitantly, PET-CT may have the potential to identify the HCA histopathologic variant with the lowest malignant and hemorrhagic potential.

PMID: 26776850 [PubMed - indexed for MEDLINE]

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Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors.

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Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors.

Curr Oncol Rep. 2016 Jan;18(1):7

Authors: Pokuri VK, Fong MK, Iyer R

Abstract
Neuroendocrine tumors are heterogeneous, rare malignancies that arise most commonly in the gastrointestinal tract and pancreas. They often secrete vasoactive substances resulting in carcinoid syndrome and the tumor cells exclusively express somatostatin receptors. Octreotide and lanreotide are the two synthetic somatostatin analogs used for the control of carcinoid symptoms and tumor progression in advanced inoperable disease. Recent pivotal trials (PROMID and CLARINET studies) established their antitumor activity. We discuss the available data to support their use as symptom controlling and antiproliferative agents. This article also reviews the guidelines (National Comprehensive Cancer Network and North American Neuro Endocrine Tumor Society), cost-analysis (suggesting the cost-effectiveness of lanreotide autogel compared to higher doses of octreotide long acting release formulation in refractory patients), and future directions of somatostatin analogs in the management of patients refractory to conventional doses of octreotide and lanreotide.

PMID: 26743514 [PubMed - indexed for MEDLINE]

http://ift.tt/2eKQs9r

Endoscopic approach to the resection of adenoid cystic carcinoma of paranasal sinuses and nasal cavity: case report and own experience.

Endoscopic approach to the resection of adenoid cystic carcinoma of paranasal sinuses and nasal cavity: case report and own experience.

Eur J Med Res. 2015 Dec 12;20:97

Authors: Wardas P, Tymowski M, Piotrowska-Seweryn A, Kaspera W, Ślaska-Kaspera A, Markowski J

Abstract
Adenoid cystic carcinoma (ACC) is a rare malignant tumor that might occur in nasal cavity and paranasal sinuses. It is characteristic for poor prognosis, especially the solid histopathological subtype of the tumor. ACC might spread along nerves and fascias and it is usually diagnosed at advanced stage. Computed tomography and magnetic resonance imaging together with fine-needle biopsy are the gold standards in the diagnostic procedure of the cancer. Surgery with adjuvant therapy are the most common methods of treatment. Among the surgical approaches, the functional endonasal sinus surgery seems to be the most appropriate and favorable way of treatment. In the study, the authors present a case of a 62-year-old patient with T4aN0M0 ACC tumor treated endoscopically at the Department of Laryngology and ENT Oncology, WSS No. 5 in Sosnowiec. The authors indicate the usefulness of FESS procedure in the treatment of malignancies of nasal cavity and paranasal sinuses. They also review the recent publications on endonasal versus open approach in similar cases. In conclusions, the authors favor endonasal approach as a mini-invasive method of surgical treatment of ACC of paranasal sinuses that results in satisfactory oncological outcome and high quality of patient's life.

PMID: 26653204 [PubMed - indexed for MEDLINE]

http://ift.tt/2eupvbx

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

Mod Pathol. 2016 Feb;29(2):122-30

Authors: Ko JS, Prieto VG, Elson PJ, Vilain RE, Pulitzer MP, Scolyer RA, Reynolds JP, Piliang MP, Ernstoff MS, Gastman BR, Billings SD

Abstract
Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

PMID: 26541273 [PubMed - indexed for MEDLINE]

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Long-Term Survival After Surgical Treatment of Thymic Carcinoma: A Retrospective Analysis from the Chinese Alliance for Research of Thymoma Database.

Long-Term Survival After Surgical Treatment of Thymic Carcinoma: A Retrospective Analysis from the Chinese Alliance for Research of Thymoma Database.

Ann Surg Oncol. 2016 Feb;23(2):619-25

Authors: Fu H, Gu ZT, Fang WT, Fu JH, Shen Y, Han YT, Yu ZT, Li Y, Tan LJ, Pang LW, Chen KN

Abstract
BACKGROUND: Thymic carcinoma is a type of rare and highly malignant tumor that originates from the thymic epithelium. Treatment and prognosis of thymic carcinoma remain controversial. We retrospectively analyzed survival data from a large-sample multicenter database in China.
METHODS: The Chinese Alliance for Research of Thymoma constructed a retrospective database of patients with thymic epithelial tumors, which enrolled 1930 patients from January 1996 to August 2013, including 329 with thymic carcinomas. In this study, we analyzed clinical, pathologic, and treatment information, measured long-term survival rates, and identified relevant prognostic factors.
RESULTS: Of 329 patients, R0 resection was performed in 211 (57.7 %), R1 in 34 (9.2 %), and R2 in 84 (22.5 %).The 3-, 5-, and 10-year survival rates were 78.3, 67.1, and 47.9 %, respectively. In univariate analysis, early Masaoka-Koga stage, R0 resection, and postoperative radiotherapy were associated with better overall survival.Early Masaoka-Koga stage and postoperative radiotherapy were also associated with disease-free survival. In multivariate analyses, R0 resection, Masaoka-Koga stage, and postoperative radiotherapy were significant prognostic factors of survival.
CONCLUSIONS: Complete resection is the preferred primary treatment for thymic carcinoma. R0 resection, early Masaoka-Koga stage, and postoperative radiotherapy are significant predictors of improved survival.

PMID: 26474558 [PubMed - indexed for MEDLINE]

http://ift.tt/2eKSfvh

MiR-573 inhibits prostate cancer metastasis by regulating epithelial-mesenchymal transition.

MiR-573 inhibits prostate cancer metastasis by regulating epithelial-mesenchymal transition.

Oncotarget. 2015 Nov 3;6(34):35978-90

Authors: Wang L, Song G, Tan W, Qi M, Zhang L, Chan J, Yu J, Han J, Han B

Abstract
The metastastic cascade is a complex process that is regulated at multiple levels in prostate cancer (PCa). Recent evidence suggests that microRNAs (miRNAs) are involved in PCa metastasis and hold great promise as therapeutic targets. In this study, we found that miR-573 expression is significantly lower in metastatic tissues than matched primary PCa. Its downregulation is correlated with high Gleason score and cancer-related mortality of PCa patients (P = 0.041, Kaplan-Meier analysis). Through gain- and loss-of function experiments, we demonstrated that miR-573 inhibits PCa cell migration, invasion and TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro and lung metastasis in vivo. Mechanistically, miR573 directly targets the fibroblast growth factor receptor 1 (FGFR1) gene. Knockdown of FGFR1 phenocopies the effects of miR-573 expression on PCa cell invasion, whereas overexpression of FGFR1 partially attenuates the functions of miR-573. Consequently, miR-573 modulates the activation of FGFR1-downstream signaling in response to fibroblast growth factor 2 (FGF2). Importantly, we showed that GATA3 directly increases miR-573 expression, and thus down-regulates FGFR1 expression, EMT and invasion of PCa cells in a miR-573-dependent manner, supporting the involvement of GATA3, miR-573 and FGFR1 in controlling the EMT process during PCa metastasis. Altogether, our findings demonstrate a novel mechanism by which miR-573 modulates EMT and metastasis of PCa cells, and suggest miR-573 as a potential biomarker and/or therapeutic target for PCa management.

PMID: 26451614 [PubMed - indexed for MEDLINE]

http://ift.tt/2eumkk5

Metabolic Mechanisms of Vocal Fatigue.

Metabolic Mechanisms of Vocal Fatigue.

J Voice. 2016 Oct 21;:

Authors: Nanjundeswaran C, VanSwearingen J, Abbott KV

Abstract
OBJECTIVE: This study aimed to identify potential metabolic mechanisms including (1) neuromuscular inefficiency, (2) cardiovascular recovery deficits, or (3) both, in individuals with complaints of vocal fatigue.
STUDY DESIGN: Within- and between-subjects group design was used in this study.
METHODS: Three groups of women participated in the study, including (1) individuals with complaints of vocal fatigue; (2) vocally healthy sedentary individuals; and (3) vocally healthy, cardiovascularly conditioned individuals. Group assignment was based on results from the Vocal Fatigue Index, laryngeal examination, and self-report regarding exercise regimens. Metabolic profiles were obtained using gas exchange measures monitored during vocal task performance (reading) at two different loudness levels, and during recovery from reading.
RESULTS: Statistical analyses did not reveal reliable group differences in metabolic cost for or recovery from vocal tasks. However, descriptive review of oxygen uptake and recovery kinetics revealed patterns indicating reliance on differential energy resources for the vocal task in individuals with vocal fatigue compared with cardiovascularly trained, vocally healthy individuals in particular. Slow oxygen uptake kinetics at task onset was a characteristic of the vocal fatigue group, indicating a general reliance on anaerobic resources to meet the demands of the vocal task, pointing to possible neuromuscular inefficiency. Individuals with vocal fatigue also demonstrated an increase in oxygen consumption following vocal task compared with cardiovascularly trained individuals, suggesting possible cardiovascular recovery deficits.
CONCLUSION: This study provides initial data relevant to possible metabolic mechanisms of vocal fatigue and the potential relevance of aerobic conditioning in individuals with such fatigue.

PMID: 27777059 [PubMed - as supplied by publisher]

http://ift.tt/2e9SDBT

Management of chest deformity caused by microtia reconstruction: Comparison of autogenous diced cartilage versus cadaver cartilage graft partial filling techniques.

Management of chest deformity caused by microtia reconstruction: Comparison of autogenous diced cartilage versus cadaver cartilage graft partial filling techniques.

J Plast Reconstr Aesthet Surg. 2016 Sep 23;:

Authors: Go JY, Kang BY, Hwang JH, Oh KS

Abstract
BACKGROUND: Efforts to prevent chest wall deformity after costal cartilage graft are ongoing. In this study, we introduce a new method to prevent donor site deformation using irradiated cadaver cartilage (ICC) and compare this method to the autogenous diced cartilage (ADC) technique.
METHODS: Forty-two pediatric patients comprised the ADC group (n = 24) and the ICC group (n = 18). After harvesting costal cartilage, the empty perichondrial space was filled with autologous diced cartilage in the ADC group and cadaver cartilage in the ICC group. Digital photographs and rib cartilage three-dimensional computed tomography (CT) data were analyzed to compare the preventive effect of donor site deformity. We compared the pre- and postoperative costal cartilage volumes using 3D-CT and graded the volumes (grade I: 0%-25%, grade II: 25%-50%, grade III: 50%-75%, and grade IV: 75%-100%).
RESULTS: The average follow-up period was 20 and 24 months in the ADC and ICC groups, respectively. Grade IV maintenance of previous costal cartilage volume was evident postoperatively in 22% of patients in the ADC group and 82% of patients in the ICC group. Intercostal space narrowing and chest wall depression were less in the ICC group. There were no complications or severe resorption of cadaver cartilage.
CONCLUSIONS: ICC support transected costal ring and prevented stability loss by acting as a spacer. The ICC technique is more effective in preventing intercostal space narrowing and chest wall depression than the ADC technique.
CLINICAL TRIAL REGISTRY: Samsung Medical Center Institution Review Board, Unique protocol ID: 2009-10-006-008. This study is also registered on PRS (ClinicalTrials.gov Record 2009-10-006).

PMID: 27777177 [PubMed - as supplied by publisher]

http://ift.tt/2e9Unen

When should axillary drains be removed? A meta-analysis of time-limited versus volume controlled strategies for timing of drain removal following axillary lymphadenectomy.

When should axillary drains be removed? A meta-analysis of time-limited versus volume controlled strategies for timing of drain removal following axillary lymphadenectomy.

J Plast Reconstr Aesthet Surg. 2016 Oct 5;:

Authors: Thomson DR, Trevatt AE, Furniss D

Abstract
BACKGROUND: Despite numerous studies over the past few decades, the optimum strategy for deciding when to remove drains following axillary lymphadenectomy remains unknown. This meta-analysis aims to compare time-limited and volume-controlled strategies for drain removal.
METHODS: A total of 584 titles were identified following a systematic literature search of EMBASE, MEDLINE, Cinahl and the Cochrane library; 6 titles met our eligibility criteria. Data were extracted and independently verified by two authors. Time-limited drain removal was defined as drain removal at <5 days; volume-controlled strategies ranged from <20 ml/24 h to <50 ml/24 h.
RESULTS: In all the studies, the time-limited approach resulted in earlier drain removal. Development of a seroma is 2.54 times more likely with early drain removal (Mantel-Haenszel Fixed Odds Ratio (OR) 2.54, p < 0.00001). However, there is no difference in infection rates between early and late drain removal (OR = 1.07, p = 0.76).
CONCLUSIONS: This meta-analysis demonstrates that a strategy of early drain removal following axillary lymphadenectomy is safe, with no difference in infection rates; however, the incidence of seroma is significantly higher, which may necessitate more demanding outpatient care. There is a need for further well-designed clinical trials to address the clinical equipoise in this common area of surgical practice.

PMID: 27777176 [PubMed - as supplied by publisher]

http://ift.tt/2e9T53n

Discrepancies between biopsy and formal excision histology of non-melanoma skin cancer.

Discrepancies between biopsy and formal excision histology of non-melanoma skin cancer.

J Plast Reconstr Aesthet Surg. 2016 Oct 5;:

Authors: Armstrong A, Hart-Pinto A, Sharma N, Hassan Z

PMID: 27777175 [PubMed - as supplied by publisher]

http://ift.tt/2e9RPx3

A Comprehensive Analysis on the Association between Tobacco-Free Betel Quid and Risk of Head and Neck Cancer in Taiwanese Men.

A Comprehensive Analysis on the Association between Tobacco-Free Betel Quid and Risk of Head and Neck Cancer in Taiwanese Men.

PLoS One. 2016;11(10):e0164937

Authors: Wu YH, Yen CJ, Hsiao JR, Ou CY, Huang JS, Wong TY, Tsai ST, Huang CC, Lee WT, Chen KC, Fang SY, Wu JL, Hsueh WT, Lin FC, Yang MW, Chang JY, Liao HC, Wu SY, Lin CL, Wang YH, Weng YL, Yang HC, Chen YS, Chang JS

Abstract
OBJECTIVES: Although betel quid (BQ) is an established risk factor of head and neck cancer (HNC), insufficiencies exist in the literature regarding the dose-response, BQ types, HNC sites, and BQ cessation. The current study was conducted to fill these insufficiencies.
MATERIALS AND METHODS: A hospital-based case-control study was conducted to evaluate the association between BQ and HNC. In-person interview was conducted to collect data on BQ chewing. The current analysis included 487 men newly diagnosed with HNC and 617 male controls who were frequency-matched to the cases by age. The association between BQ and HNC was assessed using multivariable unconditional logistic regression.
RESULTS: Ever BQ chewing was associated with an increased HNC risk regardless of the BQ types. A non-linear positive association between BQ and HNC was observed, with a steep rise in HNC risk for the first 5 pack-years or 200,000 minutes of BQ consumption. Every year of BQ cessation was associated with a 2.9% reduction in HNC risk; however, the risk did not reduce to the level of non-BQ chewers even after 20 years of BQ cessation. Eliminating BQ chewing may prevent 51.6% of HNCs, 62.6% of oral cancers, and 41.3% of pharyngeal cancers in Taiwan.
CONCLUSION: Our results supported the positive association between BQ and HNC. BQ cessation is effective in reducing HNC risk and should be encouraged. Because BQ cessation may not reduce the HNC risk to the level of non-BQ chewers, it is important to prevent the initiation of BQ chewing.

PMID: 27780233 [PubMed - in process]

http://ift.tt/2dJn011

LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer).

LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer).

PLoS One. 2016;11(10):e0164804

Authors: Simonik EA, Cai Y, Kimmelshue KN, Brantley-Sieders DM, Loomans HA, Andl CD, Westlake GM, Youngblood VM, Chen J, Yarbrough WG, Brown BT, Nagarajan L, Brandt SJ

Abstract
Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease. First, we found that the relative abundance of LMO4, LDB1, and the two SSBPs correlated very significantly in a panel of human HNSCC cell lines. Second, expression of these proteins in tumor primaries and lymph nodes involved by metastasis were concordant in 3 of 3 sets of tissue. Third, using a Matrigel invasion and organotypic reconstruct assay, CRISPR/Cas9-mediated deletion of LDB1 in the VU-SCC-1729 cell line, which is highly invasive of basement membrane and cellular monolayers, reduced tumor cell invasiveness and migration, as well as proliferation on tissue culture plastic. Finally, inactivation of the LDB1 gene in these cells decreased growth and vascularization of xenografted human tumor cells in vivo. These data show that LMO4, LDB1, and SSBP2 and/or SSBP3 regulate metastasis, proliferation, and angiogenesis in HNSCC and provide the first evidence that SSBPs control LMO4 and LDB1 protein abundance in a cancer context.

PMID: 27780223 [PubMed - in process]

http://ift.tt/2eumxnu

Platycodin D inhibits interleukin-13-induced the expression of inflammatory cytokines and mucus in nasal epithelial cells.

Platycodin D inhibits interleukin-13-induced the expression of inflammatory cytokines and mucus in nasal epithelial cells.

Biomed Pharmacother. 2016 Oct 22;84:1108-1112

Authors: Wang B, Gao Y, Zheng G, Ren X, Sun B, Zhu K, Luo H, Wang Z, Xu M

Abstract
Allergic rhinitis (AR) is a common chronic inflammatory condition of the nasal mucosal tissue. Platycodin D (PLD), a triterpenoid saponin isolated from the root of Platycodon grandiflorum, has anti-inflammatory effects in a mouse model of allergic asthma. However, the anti-inflammatory effects of PLD in the nasal mucosa have not been deeply investigated. The objective was to investigate the effect of PLD on inflammatory cytokines and mucus production from nasal epithelial cells. Our study showed that PLD inhibited the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and eotaxin in interleukin (IL)-13-stimulated RPMI2650 cells. PLD also suppressed IL-13-induced mucin 5AC (MUC5AC) expression in RPMI2650 cells. Moreover, PLD treatment prevented IL-13-induced p-NF-κB p65 expression in RPMI2650 cells, as well as MAPK signaling pathway activation. Taken together, our results provided evidence that PLD inhibits IL-13-induced the expression of inflammatory cytokines and mucus in nasal epithelial cells by inhibiting the activation of NF-κB and MAPK signaling pathways.

PMID: 27780139 [PubMed - as supplied by publisher]

http://ift.tt/2dJnT9Z

Human enterovirus and rhinovirus infections are associated with otitis media in a prospective birth cohort study.

Human enterovirus and rhinovirus infections are associated with otitis media in a prospective birth cohort study.

J Clin Virol. 2016 Oct 20;85:1-6

Authors: Seppälä E, Sillanpää S, Nurminen N, Huhtala H, Toppari J, Ilonen J, Veijola R, Knip M, Sipilä M, Laranne J, Oikarinen S, Hyöty H

Abstract
BACKGROUND: Human enteroviruses (HEVs) and rhinoviruses (HRVs) have been linked to acute otitis media (AOM).
OBJECTIVES: The present study evaluates the aforementioned association in a birth cohort setting.
STUDY DESIGN: The cohort included 286 healthy infants (191 boys) followed from birth up to the age of 2 years in the Type 1 Diabetes Prediction and Prevention study in Finland. Stool samples were collected monthly and analyzed for the presence of HRV and HEV RNA using RT-PCR. Clinical symptoms were recorded by a questionnaire every 3-6 months.
RESULTS: Altogether 610 AOM episodes were reported during the follow-up. 9.8% of the stool samples were positive for HRV and 6.8% for HEV. HRV positivity peaked at the age of 3-6 months declining gradually after this age, whereas HEV positivity peaked later, at the age of 12-24 months. The risk of AOM was increased in children who were HEV positive at least once at the age of 6-12 months (OR 2.2 [95%CI 1.1-4.2], P=0.023) or who were HRV positive at least once at the age of 18-24 months (OR 2.3 [95%CI 1.0-5.2], P=0.042). Having an older sibling, short breast-feeding and maternal smoking during pregnancy were also significantly associated with AOM.
CONCLUSIONS: HRV and HEV infections are frequent during the first months of life. The observed trend for increased risk of AOM in HRV and HEV positive children is in line with the results from hospital series suggesting that these viruses may play an independent role in the pathogenesis of AOM.

PMID: 27780081 [PubMed - as supplied by publisher]

http://ift.tt/2eun4WL

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis.

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis.

Head Neck. 2016 Oct 25;:

Authors: Kang SY, Deshpande SS, Zheutlin AR, Donneys A, Rodriguez JJ, Nelson NS, Felice PA, Chepeha DB, Buchman SR

Abstract
BACKGROUND: The purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO).
METHODS: Thirty-four rats were divided into 3 groups. The control group underwent DO and the radiation control group underwent radiotherapy (RT) before DO. The PTH group underwent RT and received PTH during DO. Quantitative histology and histomorphometry were performed.
RESULTS: RT resulted in a depletion of osteocytes and increase in empty lacunae. Treatment with PTH resulted in an increase in osteocyte counts and decrease in empty lacunae (p < .05), restoring osteocytes to levels seen in nonradiated bone (p = .121). RT decreased bone volume to tissue volume (BV-TV) ratio and increased osteoid volume to tissue volume (OV-TV) ratio, signifying increased immature bone formation. PTH treatment restored OV-TV ratio to that observed in nonradiated bone.
CONCLUSION: PTH treatment of irradiated bone enhanced bone regeneration and restored osteocyte counts and OV-TV ratio to levels comparable to nonradiated bone. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 27779806 [PubMed - as supplied by publisher]

http://ift.tt/2dJkCau

Hearing Changes After Intratympanically Applied Steroids for Primary Therapy of Sudden Hearing Loss: A Meta-analysis Using Mathematical Simulations of Drug Delivery Protocols.

Hearing Changes After Intratympanically Applied Steroids for Primary Therapy of Sudden Hearing Loss: A Meta-analysis Using Mathematical Simulations of Drug Delivery Protocols.

Otol Neurotol. 2016 Oct 21;

Authors: Liebau A, Pogorzelski O, Salt AN, Plontke SK

Abstract
OBJECTIVE: Controlled and uncontrolled studies with primary intratympanic or combined intratympanic and systemic application of glucocorticosteroids for idiopathic sudden hearing loss were analyzed by means of a meta-analysis in an attempt to establish optimal local drug delivery protocols.
STUDY DESIGN: A total of 25 studies with 28 treatment groups between January 2000 and June 2014 were selected that adequately described drug delivery protocols. Cochlear drug levels were calculated by a validated computer model of drug dispersion in the inner ear fluids based on the concentration and volume of glucocorticoids applied, the time the drug remained in the middle ear, and the specific timing of injections. Various factors were compared with hearing outcome, including baseline data, individual parameters of the application protocols, calculated peak concentration (Cmax), and total dose (area under the curve).
RESULTS: There was no dependence of hearing outcome on individual parameters of the application protocol, Cmax, or area under the curve. Final hearing threshold was notably independent of delay of treatment.
CONCLUSION: During primary intratympanic or combined steroid therapy of idiopathic sudden hearing loss, the tendency toward early treatment having a positive effect on hearing improvement is thought to be a "sham effect," likely related to spontaneous recovery. Change in pure-tone average may not be an adequate outcome parameter to assess effectiveness of the intervention, as it depends on the degree of initial hearing loss. Final pure-tone average provides a better alternative.

PMID: 27779563 [PubMed - as supplied by publisher]

http://ift.tt/2eunf4f

Implantation of Bone Anchored Hearing Devices Through a Minimal Skin Punch Incision Versus the Epidermal Flap Technique.

Implantation of Bone Anchored Hearing Devices Through a Minimal Skin Punch Incision Versus the Epidermal Flap Technique.

Otol Neurotol. 2016 Oct 21;

Authors: Dumon T, Wegner I, Sperling N, Grolman W

Abstract
OBJECTIVE: To compare the minimal skin punch incision without additional skin incision or soft tissue reduction with the epidermal flap technique and soft tissue reduction, for the implantation of percutaneous bone-anchored hearing devices.
STUDY DESIGN: Prospective cohort study.
SETTING: Tertiary care referral center.
SUBJECTS AND METHODS: Two hundred seventeen patients underwent 220 implantations. Sixty five cases underwent implantation by means of a skin punch resection without soft tissue reduction (punch group) and 155 cases underwent epidermal flap and soft tissue reduction (dermatome group). Main outcome measures were duration of surgery, perioperative adverse events, skin tolerance, and revision surgery.
RESULTS: The duration of surgery was shorter in the punch group (p < 0.001). The percentage of normal to moderate skin reactions, by Holgers classification, was higher in the punch group (90%) than in the dermatome group (84%). No severe reactions occurred in the punch group, but did occur in 7% in the dermatome group. These differences, although clinically important, did not reach statistical significance (p = 0.071). The rate of revision surgeries was not significantly different between the two groups. The indication for revision was different: mainly for skin issues in the dermatome group, against implant dislocation in the punch group.
CONCLUSION: The implantation of the currently available percutaneous bone-anchored hearing implants with a minimal skin punch resection shortened duration of surgery and improved postoperative appearance, while preserving a good skin tolerance. In the punch group, there were less skin issues leading to revision surgery, however we did observe more implant dislocations needing revision surgery.

PMID: 27779562 [PubMed - as supplied by publisher]

http://ift.tt/2dJpTPi

Nystagmus at the Onset of Vertiginous Attack in Ménière's Disease.

Nystagmus at the Onset of Vertiginous Attack in Ménière's Disease.

Otol Neurotol. 2016 Oct 21;

Authors: Hirai C, Yamamoto Y, Takeda T, Tasaki A, Inaba Y, Kiyokawa Y, Suzuki Y, Tsutsumi T

Abstract
OBJECTIVE: To clarify the direction and characteristics of nystagmus at the onset of a vertiginous attack in Ménière's disease.
PATIENTS: Two patients with Ménière's disease, whose nystagmus at the onset of a vertiginous attack was recorded using electronystagmography.
INTERVENTIONS: Diagnostic.
MAIN OUTCOME MEASURES: Electronystagmographic recordings of nystagmus.
RESULTS: In both patients, nystagmus was directed toward the affected side over the entire course of the vertiginous attack. One patient experienced a severe sensation of vertigo and exhibited strong nystagmus from the onset of the attack. The other patient reported a mild sensation of vertigo, which was accompanied by intermittent nystagmus.
CONCLUSIONS: Vertiginous attacks in Ménière's disease are accompanied by irritative nystagmus. The intensity and characteristics (e.g., continuous or intermittent expression) of the nystagmus may be associated with pathophysiological severity.

PMID: 27779561 [PubMed - as supplied by publisher]

http://ift.tt/2eukiR0

Cost Analysis of Cerebrospinal Fluid Leaks and Cerebrospinal Fluid Leak Prevention in Patients Undergoing Cerebellopontine Angle Surgery.

Cost Analysis of Cerebrospinal Fluid Leaks and Cerebrospinal Fluid Leak Prevention in Patients Undergoing Cerebellopontine Angle Surgery.

Otol Neurotol. 2016 Oct 21;

Authors: Chern A, Hunter JB, Bennett ML

Abstract
OBJECTIVE: To determine if cranioplasty techniques following translabyrinthine approaches to the cerebellopontine angle are cost-effective.
STUDY DESIGN: Retrospective case series.
PATIENTS: One hundred eighty patients with available financial data who underwent translabyrinthine approaches at a single academic referral center between 2005 and 2015.
INTERVENTION: Cranioplasty with a dural substitute, layered fat graft, and a resorbable mesh plate secured with screws Main Outcome Measures: billing data was obtained for each patient's hospital course for translabyrinthine approaches and postoperative cerebrospinal fluid (CSF) leaks.
RESULTS: One hundred nineteen patients underwent translabyrinthine approaches with an abdominal fat graft closure, with a median cost of $25759.89 (range, $15885.65-$136433.07). Sixty-one patients underwent translabyrinthine approaches with a dural substitute, abdominal fat graft, and a resorbable mesh for closure, with a median cost of $29314.97 (range, $17674.28-$111404.55). The median cost of a CSF leak was $50401.25 (range, $0-$384761.71). The additional cost of a CSF leak when shared by all patients who underwent translabyrinthine approaches is $6048.15. The addition of a dural substitute and a resorbable mesh plate after translabyrinthine approaches reduced the CSF leak from 12 to 1.9%, an 84.2% reduction, and a median savings per patient of $2932.23. Applying our cohort's billing data to previously published cranioplasty techniques, costs, and leak rate improvements after translabyrinthine approaches, all techniques were found to be cost-effective.
CONCLUSION: Resorbable mesh cranioplasty is cost-effective at reducing CSF leaks after translabyrinthine approaches. Per our billing data and achieving the same CSF leak rate, cranioplasty costs exceeding $5090.53 are not cost-effective.

PMID: 27779560 [PubMed - as supplied by publisher]

http://ift.tt/2dJlhZG

Change in Psychosocial Health Status Over 5 Years in Relation to Adults' Hearing Ability in Noise.

Change in Psychosocial Health Status Over 5 Years in Relation to Adults' Hearing Ability in Noise.

Ear Hear. 2016 Nov/Dec;37(6):680-689

Authors: Stam M, Smit JH, Twisk JW, Lemke U, Smits C, Festen JM, Kramer SE

Abstract
OBJECTIVES: The aim of this study was to establish the longitudinal relationship between hearing ability in noise and psychosocial health outcomes (i.e., loneliness, anxiety, depression, distress, and somatization) in adults aged 18 to 70 years. An additional objective was to determine whether a change in hearing ability in noise over a period of 5 years was associated with a change in psychosocial functioning. Subgroup effects for a range of factors were investigated.
DESIGN: Longitudinal data of the web-based Netherlands Longitudinal Study on Hearing (NL-SH) (N = 508) were analyzed. The ability to recognize speech in noise (i.e., the speech-reception-threshold [SRTn]) was measured with an online digit triplet test at baseline and at 5-year follow-up. Psychosocial health status was assessed by online questionnaires. Multiple linear regression analyses and longitudinal statistical analyses (i.e., generalized estimating equations) were performed.
RESULTS: Poorer SRTn was associated longitudinally with more feelings of emotional and social loneliness. For participants with a high educational level, the longitudinal association between SRTn and social loneliness was significant. Changes in hearing ability and loneliness appeared significantly associated only for specific subgroups: those with stable pattern of hearing aid nonuse (increased emotional and social loneliness), who entered matrimony (increased social loneliness), and low educational level (less emotional loneliness). No significant longitudinal associations were found between hearing ability and anxiety, depression, distress, or somatization.
CONCLUSIONS: Hearing ability in noise was longitudinally associated with loneliness. Decline in hearing ability in noise was related to increase in loneliness for specific subgroups of participants. One of these subgroups included participants whose hearing deteriorated over 5 years, but who continued to report nonuse of hearing aids. This is an important and alarming finding that needs further investigation.

PMID: 27779518 [PubMed - in process]

http://ift.tt/2eule8h

Evaluation of I-Gel(™) size 2 airway in different degrees of neck flexion in anesthetized children - a prospective, self-controlled trial.

Evaluation of I-Gel(™) size 2 airway in different degrees of neck flexion in anesthetized children - a prospective, self-controlled trial.

Paediatr Anaesth. 2016 Oct 25;:

Authors: Jain D, Ghai B, Gandhi K, Banerjee G, Bala I, Samujh R

Abstract
BACKGROUND: A previous study by our group demonstrated an increase in oropharyngeal leak pressures and a deterioration of ventilation in maximum neck flexion with the I-Gel(™) . To ascertain the optimal degree of neck flexion which increases OPLP without compromising ventilation we conducted a prospective self-controlled trial with the I-Gel(™) in different degrees of neck flexion in anesthetized paralyzed children.
METHODOLOGY: The I-gel(™) was inserted in 60 children undergoing inhalation induction with muscle paralysis for routine general anesthesia. Recordings of peak inspiratory pressures (PIP) at flexion of 15°, 30°, and 45° were taken as the primary outcome. Expired tidal volume, ventilation scoring, fiberoptic gradings, and OPLP in different degrees of flexion were recorded as secondary outcomes.
RESULTS: There was a significant increase in mean PIP in cm H2 O at flexion 30° [13.3 (95% CI 12.8-13.8) cm H2 O, P < 0.001] and 45° flexion (16.5 [15.9-17.1] cm H2 O, P < 0.001) compared to neutral. A decrease in the expired tidal volume was seen at flexion of 30° (7.6 [7.3-7.8] cm H2 O, P = 0.00) and 45° (7.6 [7.3-7.8] cm H2 O, P = 0.00). There was deterioration of ventilation score, mean [range] at 30° flexion 2[0-3], and 45° flexion 1[0-3] compared to the neutral 3[2-3]. There was a significant increase in OPLP with an increase in degree of flexion.
CONCLUSION: We conclude that 15° neck flexion can safely be applied without compromising ventilation with the I-Gel(™) in anesthetized paralyzed children. However, Flexion of 30° or more warrants caution or the use of alternative devices like an endotracheal tube due to increase in PIP and worsening of ventilation score.

PMID: 27779349 [PubMed - as supplied by publisher]

http://ift.tt/2dJjvHX

Non-targeted transcriptomic effects upon thyroid irradiation: similarity between in-field and out-of-field responses varies with tissue type.

Non-targeted transcriptomic effects upon thyroid irradiation: similarity between in-field and out-of-field responses varies with tissue type.

Sci Rep. 2016 Oct 25;6:30738

Authors: Langen B, Rudqvist N, Spetz J, Swanpalmer J, Helou K, Forssell-Aronsson E

Abstract
Non-targeted effects can induce responses in tissues that have not been exposed to ionizing radiation. Despite their relevance for risk assessment, few studies have investigated these effects in vivo. In particular, these effects have not been studied in context with thyroid exposure, which can occur e.g. during irradiation of head and neck tumors. To determine the similarity between in-field and out-of-field responses in normal tissue, we used a partial body irradiation setup with female mice where the thyroid region, the thorax and abdomen, or all three regions were irradiated. After 24 h, transcriptional regulation in the kidney cortex, kidney medulla, liver, lungs, spleen, and thyroid was analyzed using microarray technology. Thyroid irradiation resulted in transcriptional regulation in the kidney medulla and liver that resembled regulation upon direct exposure of these tissues regarding both strength of response and associated biological function. The kidney cortex showed fewer similarities between the setups, while the lungs and spleen showed little similarity between in-field and out-of-field responses. Interestingly, effects were generally not found to be additive. Future studies are needed to identify the molecular mechanisms that mediate these systemic effects, so that they may be used as targets to minimize detrimental side effects in radiotherapy.

PMID: 27779251 [PubMed - in process]

http://ift.tt/2eujbAQ

Use of new targeted cancer therapies in children: effects on dental development and risk of jaw osteonecrosis: a review.

Use of new targeted cancer therapies in children: effects on dental development and risk of jaw osteonecrosis: a review.

J Oral Pathol Med. 2016 Oct 25;:

Authors: Hernandez M, Phulpin B, Mansuy L, Droz D

Abstract
New targeted cancer therapies such as bisphosphonates, denosumab and bevacizumab are routinely used in adult for the past decades. Their introduction into pediatric medicine is more recent that means there is a paucity of data on long-term effects on dental development and on the risk of osteonecrosis of jaw. This paper aims to outline adverse effects of new targeted cancer therapies on oral cavity including dental abnormalities observed in pediatric population treated with these molecules and the risk of osteonecrosis of the jaw (ONJ). The impact of bisphosphonates and denosumab on bone remodeling (inhibition of osteoclasts) could interfere with teeth exfoliation and eruption processes, causing a tooth eruption delay. This hypothesis was confirmed, bisphosphonates-treated rats presented tooth eruption delay and bisphosphonate therapy was associated with a mean delay of 1.67 years in tooth eruption in children with osteogenesis imperfecta. Another study showed that the inhibition of RANK/RANKL by denosumab was associated with a lack of tooth eruption in animals. Several animal studies reported that bisphosphonate could also induce dental abnormalities including defective amelogenesis and dentinogenesis in rats but there is no evidence of such effects in children, only one case of enamel hypoplasia in a child treated for idiopathic arterial calcification with bisphosphate was reported. To date, there have been no reported case of ONJ in children treated with bisphosphonates, denosumab or bevacizumab. This article is protected by copyright. All rights reserved.

PMID: 27778394 [PubMed - as supplied by publisher]

http://ift.tt/2dJjBPR

Evaluating organ preservation outcome as treatment endpoint for T1aN0 glottic cancer.

Evaluating organ preservation outcome as treatment endpoint for T1aN0 glottic cancer.

Laryngoscope. 2016 Oct 25;:

Authors: Low TH, Yeh D, Zhang T, Araslanova R, Hammond JA, Palma D, Read N, Venkatesan V, MacNeil SD, Yoo J, Nichols A, Fung K

Abstract
OBJECTIVES/HYPOTHESIS: Common endpoints in reporting the outcomes for early glottic cancer do not highlight the importance of organ preservation. We evaluated the treatment outcomes among patients with T1aN0 laryngeal cancer with laryngectomy-free disease-specific survival (LFS-DSS), which is defined as time to total laryngectomy or time to death from cancer cause, against all other endpoints.
STUDY DESIGN: Outcome research on an institutional database.
METHODS: A retrospective review covered all consecutive patients from 2003 to 2013. Patients with T1a laryngeal squamous cell carcinoma (SCC) were offered the options of either radiation treatment (RT) or transoral laser microsurgery (TLM). Tumor control, survival outcomes, standard definition laryngectomy-free survival (LFS), and LFS-DSS were calculated.
RESULTS: There were 105 patients, of whom 53 were treated with TLM and 52 were treated with RT. There were 11 recurrences within the TLM group, of which four were successfully salvaged with repeated TLM and two were salvaged with RT. Among the four recurrences within the RT group, all four patients had salvage total laryngectomies. The 5-year overall survival for patients treated with TLM versus RT was 86% versus 85% (P = .887), disease-free survival was 69% versus 78% (P = .151), LFS was 65% versus 77% (P = .198), LFS-DSS was 100% versus 88% (P = .030), and ultimate locoregional control was 100% in both groups.
CONCLUSIONS: Patients with T1aN0 glottic SCC treated with RT or TLM have similar survival outcomes. Patients with T1a tumor treated with TLM have better organ preservation compared to RT, when measured with LFS-DSS.
LEVEL OF EVIDENCE: 4. Laryngoscope, 2016.

PMID: 27778345 [PubMed - as supplied by publisher]

http://ift.tt/2dJin7l

Toxicity, pharmacokinetics and metabolism of a novel inhibitor of IL-6-induced STAT3 activation.

Toxicity, pharmacokinetics and metabolism of a novel inhibitor of IL-6-induced STAT3 activation.

Cancer Chemother Pharmacol. 2016 Oct 24;

Authors: Kiesel BF, Parise RA, Guo J, Huryn DM, Johnston PA, Colombo R, Sen M, Grandis JR, Beumer JH, Eiseman JL

Abstract
PURPOSE: The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) promotes gene transcription involved in cancer, and its activation by IL-6 is found in head and neck squamous cell carcinoma. Four triazolothiadizine STAT3 pathway inhibitors were evaluated to prioritize a single compound for in vivo examination.
METHODS: Metabolic stability in mouse liver microsome incubation was used to evaluate four triazolothiadizine analogues, and UPCDC-10205 was administered to mice IV as single or multiple doses to evaluate toxicity. Single-dose pharmacokinetics (PK), bioavailability and metabolism were studied after IV 4 mg/kg, PO 4 mg/kg, or PO 30 mg/kg suspension in 1% carboxymethyl cellulose. Mice were euthanized between 5 min to 24 h after dosing, and plasma and tissues were analyzed by LC-MS. Non-compartmental PK parameters were determined.
RESULTS: Of the four triazolothiadizine analogues evaluated, UPCDC-10205 was metabolically most stable. The maximum soluble dose of 4 mg/kg in 10% Solutol™ was not toxic to mice after single and multiple doses. PK analysis showed extensive tissue distribution and rapid plasma clearance. Bioavailability was ~5%. A direct glucuronide conjugate was identified as the major metabolite which was recapitulated in vitro.
CONCLUSIONS: Rapid clearance of UPCDC-10205 was thought to be the result of phase II metabolism despite its favorable stability in a phase I in vitro metabolic stability assay. The direct glucuronidation explains why microsomal stability (reflective of phase I metabolism) did not translate to in vivo metabolic stability. UPCDC-10205 did not demonstrate appropriate exposure to support efficacy studies in the current formulation.

PMID: 27778071 [PubMed - as supplied by publisher]

http://ift.tt/2dJimAi

Transcription factor Dlx3 induces aryl hydrocarbon receptor promoter activity.

Transcription factor Dlx3 induces aryl hydrocarbon receptor promoter activity.

Biochem Biophys Rep. 2016 Sep;7:353-360

Authors: Shin JH, Haggadone MD, Sunwoo JB

Abstract
The Distal-less (Dlx) homeobox transcription factors (TFs) play a prominent role in regulating multiple facets of vertebrate biology. Though widely studied as mediators of tissue development, recent work has uncovered a role for this TF family in modulating the vertebrate hematopoietic compartment. Pertinent to our study, murine Dlx1-3 are expressed in an innate lymphocyte population known as natural killer (NK) cells, and they are implicated to assume a functional role in the NK cell maturation pathway. However, Dlx target genes are poorly understood. In Drosophila, the invertebrate Dlx ortholog Distal-less (Dll) regulates another transcription factor called Spineless (ss), which is critical for specifying distal antennal segments. Importantly, the vertebrate ortholog of ss is the aryl hydrocarbon receptor (AhR), a transcription factor recently shown to be important in the regulation of a number of immune cell subsets, including NK cells. Given these findings, we investigated whether Dlx TF family members might analogously regulate AhR in an NK cell context. Our results demonstrate that Dlx3 is constitutively co-expressed with AhR in murine and human CD127(+) NK cells. Critically, we show that Dlx3 induces AhR promoter activity by binding to a regulatory region that resides ~5.5 kb upstream of the transcriptional start site. This mechanism is functionally relevant, as Dlx3 expression in human NK cells significantly enhances TF activity at AhR DNA-binding elements (Xenobiotic Responsive Elements, XREs). Thus, our study defines Dlx3 as a positive regulator of the aryl hydrocarbon receptor.

PMID: 27777986 [PubMed - in process]

http://ift.tt/2dJmm3Q

Review on Factors Affecting Targeting Accuracy of Deep Brain Stimulation Electrode Implantation between 2001 and 2015

Background: Accurate implantation of a depth electrode into the brain is of the greatest importance in deep brain stimulation (DBS), and various stereotactic systems have been developed for electrode implantation. However, an updated analysis of depth electrode implantation in the modern era of DBS is lacking. Objective: This study aims at providing an updated review on targeting accuracy of DBS electrode implantation by analyzing contemporary DBS electrode implantation operations from the perspective of precision engineering. Methods: Eligible articles with information on targeting accuracy of DBS electrode implantation were searched in the PubMed database. Results: An average targeting error of DBS electrode implantation is reported to decrease toward 1 mm; the standard deviation of targeting error is decreasing toward 0.5 mm. Targeting accuracy is not only found to be affected by individual surgical steps, but also systematically affected by the architecture of the implantation operation. Conclusion: A systematic strategy should be adopted to further improve the targeting accuracy of depth electrode implantation. Attention should be paid to optimizing the whole electrode implantation operation, which can help minimize error accumulation or amplification throughout the serially connected procedures for DBS electrode implantation.
Stereotact Funct Neurosurg 2016;94:351-362

http://ift.tt/2eEyozP

Deep Brain Stimulation of the Caudal Zona Incerta: Tremor Control in Relation to the Location of Stimulation Fields

Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.
Stereotact Funct Neurosurg 2016;94:363-370

http://ift.tt/2e9OYE8

Rapid attentional selection processes operate independently and in parallel for multiple targets

Publication date: Available online 25 October 2016
Source:Biological Psychology
Author(s): Anna Grubert, Martin Eimer
The question whether multiple objects are selected serially or in parallel remains contentious. Previous studies employed the N2pc component as a marker of attentional selection to show that multiple selection processes can be activated concurrently. The present study demonstrates that the concurrent selection of multiple targets reflects genuinely parallel processing that is unaffected by whether or when an additional selection process is elicited simultaneously for another target. Experiment 1 showed that N2pc components triggered during the selection of a colour-defined target were not modulated by the presence versus absence of a second target that appeared in close temporal proximity. Experiment 2 revealed that the same rapid parallel selection processes were elicited regardless of whether two targets appeared simultaneously or in two successive displays. Results show that rapid attentional selection processes within the first 200ms after stimulus onset can be triggered in parallel for multiple objects in the visual field.

http://ift.tt/2f6DKVQ

Intestinal Metaplasia Of Appendiceal Endometriosis Is Not Uncommon And May Mimic Appendiceal Mucinous Neoplasm

Publication date: Available online 25 October 2016
Source:Pathology - Research and Practice
Author(s): Monika Vyas, Serena Wong, Xuchen Zhang
Endometriosis of the appendix can be an incidental finding or a cause of appendicitis, intussusception, perforation or retention mucocele. Intestinal metaplasia of appendiceal endometriosis may occur, which can lead to a misdiagnosis of low-grade appendiceal mucinous neoplasm. On a retrospective search of the pathology database from 2001 to 2015, we identified 78 appendiceal endometriosis cases and intestinal metaplasia was present in 10/78 (13%) cases. In most of the cases (90%), the foci of intestinal metaplasia were mainly localized close to the mucosa. Intestinal and endometrial hybrid glands were present in 9/10 (90%) cases. These cases were often associated with marked appendiceal distortion, luminal obliteration and mass formation, causing concern for a mucinous neoplasm clinically and pathologically. Our findings indicate that intestinal metaplasia in appendiceal endometriosis is not an uncommon phenomenon, which can be mistaken for a mucinous neoplasm. Endometriosis should be kept in mind when a diagnosis of appendiceal mucinous neoplasm is made, especially in a young woman with a clinical history of endometriosis.

http://ift.tt/2eFmiDF

Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications

Publication date: Available online 25 October 2016
Source:Pathology - Research and Practice
Author(s): Ayodeji O.J. Agboola, Henry O. Ebili, Victoria O. Iyawe, Adekunbiola A.F. Banjo, Babatunde A. Salami, Emad A. Rakha, Chrstopher C. Nolan, Ian O. Ellis, Andrew R. Green
Ku 70/80 is a regulator of the Non-Homologous End Joining (NHEJ) roles in clinicopathological features, and has prognostic significance in breast cancer (BC) in Caucasian populations. However, its significance in the Nigerian BC population, which is characterized by a higher rate of the triple-negative and basal phenotype, p53 mutation rate and BRCA1 deficiency, still needs to be investigated. We hypothesize that Ku70/80 expression shows adverse expression in Nigerian BC and, furthermore, that it is likely to have a therapeutic implication for Black BC management.This study investigated the biological, clinicopathological and prognostic significance of Ku 70/80 expression in a BC cohort from a Nigerian population. Ku 70/80 expression was determined in 188 well-characterized formalin-fixed, paraffin-embedded (FFPE) BC samples using tissue microarray and immunohistochemistry. Ku 70/80 expression was correlated with clinicopathological, molecular and prognostic characteristics of patients.Ku 70/80 was expressed in 113 (60.1%) tumors, and was positively associated with metastatic disease, triple-negative and basal phenotype, BRCA1 down regulators (MTA-1 and ID4), p-cadherin, PI3KCA and p53 expression. It inversely correlated with BRCA1, BRCA2, BARD1 and p27. Ku 70/80 was predictive of breast cancer-specific survival in multivariate analysis, but not of disease-free interval.This study demonstrated that Ku 70/80 expression is associated with triple negativity and down-regulation of the homologous recombination pathway of DNA repair. Therefore, the development of novel drugs to target KU70/80 may improve the patients' outcome in the treatment of Black BC.

http://ift.tt/2eExkff

SMARCB1/INI1-deficient sinonasal carcinoma shows methylation of RASSF1 gene: A clinicopathological, immunohistochemical and molecular genetic study of a recently described entity

Publication date: Available online 25 October 2016
Source:Pathology - Research and Practice
Author(s): Jan Laco, Marcela Chmelařová, Hana Vošmiková, Kateřina Sieglová, Ivana Bubancová, Pavel Dundr, Kristýna Němejcová, Jaroslav Michálek, Petr Čelakovský, Radovan Mottl, Igor Sirák, Milan Vošmik, Aleš Ryška
The aim of the study was detailed clinicopathological investigation of SMARCB1/INI1-deficient sinonasal carcinomas, including molecular genetic analysis of mutational status and DNA methylation of selected protooncogenes and tumor suppressor genes by means of next generation sequencing (NGS) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA).A total of 4/56 (7%) cases of SMARCB1/INI1-deficient carcinomas were detected among 56 sinonasal carcinomas diagnosed over a 19year period using immunohistochemical screening. The series comprised 3 males and 1 female, aged 27–76 years (median 64 years). All tumors arose in the nasal cavity. Three neoplasms were diagnosed in advanced stage pT4. During the follow-up period (range 14–111 months (median 72 months)), three tumors recurred locally, but none of the patients developed regional or distant metastases. Ultimately, two patients died due to the tumor.Microscopically, all tumors consisted of infiltrating nests of polygonal basaloid cells with a variable component of rhabdoid cells with eosinophilic cytoplasm. Immunohistochemically, there was almost diffuse expression of cytokeratins (CK), p16, p40 and p63 in all cases, while expression of CK5/6, CK7 and vimentin was only focal or absent. The detection of NUT gave negative results. In three cases, the absence of SMARCB1/INI1 expression was due to deletion of SMARCB1/INI1 gene. Methylation of SMARCB1/INI1 gene was not found. One tumor harbored HPV18 E6/E7 mRNA.All 12 genes (BRAF, BRCA1, BRCA2, KIT, EGFR, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, RET, and ROS1) tested for mutations using NGS were wild-type. Regarding DNA methylation, all four SMARCB1/INI1-deficient tumors showed methylation of RASSF1 gene by means of MS-MLPA. There was a statistically significant difference in RASSF1 gene methylation between SMARCB1/INI1-deficient and SMARCB1/INI1-positive tumors (p=0.0095). All other examined genes (ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, and VLH) were unmethylated.In summary, we described four cases of SMARCB1/INI1-deficient sinonasal carcinoma with detailed clinicopathological data indicating that these tumors can be regarded as a distinct entity with aggressive behaviour. For the first time, we performed analysis of DNA methylation in SMARCB1/INI1-deficient sinonasal carcinomas, reporting on significantly higher methylation of RASSF1 gene in this neoplasm.

http://ift.tt/2eFmin9

Histomorphological Changes in Endometriosis in a patient treated with Ulipristal: A Case Report

Publication date: Available online 25 October 2016
Source:Pathology - Research and Practice
Author(s): J. Bateman, O. Bougie, S. Singh, S. Islam
BackgroundSelective progesterone receptor modulators have shown efficacy in the treatment of endometriosis, however they are not currently licensed in Canada for this purpose. Their histomorphological effects have been well documented in the endometrium, but not in endometriosis.Case ReportThe patient presented with uterine fibroids and heavy menstrual bleeding, and was treated with ulipristal acetate over three 90-day courses. She eventually elected to undergo definitive surgical management. On pathological examination, she was found to have a focus of endometriosis in the para-tubal soft tissue showing a morphology similar to progesterone receptor modulator associated endometrial changes (PAEC).ConclusionsTo our knowledge this is the first reported case of PAEC involving a focus of endometriosis. This case demonstrates histomorphological evidence of the effects of ulipristal acetate on endometriosis, and thus provides evidence of a pharmacological effect.

http://ift.tt/2eEwajU

SMAD-4 gene expression in human colorectal cancer; comparison with some clinical and pathological parameters

Publication date: Available online 26 October 2016
Source:Pathology - Research and Practice
Author(s): Agnieszka Wosiak, Damian Wodziński, Marcin Kolasa, Aleksandra Sałagacka Kubiak, Ewa Balcerczak
The aim of this study was to evaluate the expression of SMAD-4 gene in cases of colorectal cancer and to link the obtained data with the development of this disease. SMAD-4 gene is responsible for the control of many important cellular processes, for example prevention of excessive epithelial cell growth and divisions. This suppressor gene is located on chromosome 18 within the region with frequent genetic losses in colorectal cancer. Inactivation of this gene is commonly found in pancreatic cancer where the SMAD-4 gene lost in the expression has been associated with a poor prognosis in this cancer. However, the role of SMAD-4 gene in other cancers has not been completely explained, therefore in the present study we tried to find the role of this gene in colon cancer. The relative expression level of SMAD-4 gene was determined by real-time PCR for 80 cases of colorectal cancer. The obtained results for SMAD-4 expression were compared with many clinical and pathological variables (such as the size and depth of primary tumour penetration, presence of the metastases, stage of cancer, histological grade or overall survival). It was found that the level of SMAD-4 gene expression was not associated with the analyzed parameters of clinical staging. The lack of dependence can be caused by slight differences within the study group in view of parameters correlated with invasive colon cancer. Further analysis in this direction is needed.

http://ift.tt/2eFmYsN

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! # Ola via Alexandros G.Sfakianakis on Inoreader

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Τετάρτη 26 Οκτωβρίου 2016

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