Multiple cutaneous reticulohistiocytosis with T-cell large granular lymphocyte clonopathy

Abstract

A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68⁺ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3⁺, CD8⁺ CD57⁺ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.

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Unusual clinical umbilical hernia: pitfall

Description

A 75-year-old alcoholic male patient with severe malnutrition was admitted to the hospital with the diagnosis of pneumonia. The finding of a symptomatic umbilical hernia on patient examination mandated a surgical consultation with the question of an operative hernia repair.

Clinically, the abdomen was distended with spider angiomas. Palpation of the umbilical hernia was painless. The hernia content was not reducible. A suspicious murmur (Cruveilhier-Baumgarten murmur) was identified on auscultation of the umbilicus (figure 1). The abdominal CT scan showed signs of portal hypertension. A large recanalised paraumbilical vein coursing from the left side of the portal vein through the falciform ligament and draining into a large umbilical varicose vein was visible. An enlarged right inferior epigastric vein originating from the umbilical varicose vein drained into the right femoral vein. The hernial sac contained only the umbilical varicose (figure 2A,B,C). On further investigation,...

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Biologics,Biologic Response Modifiers,Biopharmaceutical.

http://otorhinolarygology.blogspot.com/2017/04/biologicsbiologic-response.html

Major kinds of biopharmaceuticals include:

Blood factors (Factor VIII and Factor IX)

Thrombolytic agents (tissue plasminogen activator)

Hormones (insulin, glucagon, growth hormone, gonadotrophins)

Haematopoietic growth factors (Erythropoietin, colony stimulating factors)

Interferons (Interferons-α, -β, -γ)

Interleukin-based products (Interleukin-2)

Vaccines (Hepatitis B surface antigen)

Monoclonal antibodies (Various)

Additional products (tumour necrosis factor, therapeutic enzymes)

Research and development investment in new medicines by the biopharmaceutical industry stood at $65.2 billion in 2008.[11] A few examples of biologics made with recombinant DNA technology include:

USAN/INN Trade name Indication Technology Mechanism of action

abatacept Orencia rheumatoid arthritis immunoglobin CTLA-4 fusion protein T-cell deactivation

adalimumab Humira rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Ulcerative Colitis, Crohn's disease monoclonal antibody TNF antagonist

alefacept Amevive chronic plaque psoriasis immunoglobin G1 fusion protein incompletely characterized

erythropoietin Epogen anemia arising from cancer chemotherapy, chronic renal failure, etc. recombinant protein stimulation of red blood cell production

etanercept Enbrel rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis recombinant human TNF-receptor fusion protein TNF antagonist

infliximab Remicade rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Ulcerative Colitus, Crohn's disease monoclonal antibody TNF antagonist

trastuzumab Herceptin breast cancer humanized monoclonal antibody HER2/neu (erbB2) antagonist

ustekinumab Stelara psoriasis humanized monoclonal antibody IL-12 and IL-23 antagonist

denileukin diftitox Ontak cutaneous T-cell lymphoma (CTCL) Diphtheria toxin engineered protein combining Interleukin-2 and Diphtheria toxin Interleukin-2 receptor binder

golimumab Simponi rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Ulcerative colitis monoclonal antibody TNF antagonist

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Future Meetings

Thyroid Apr 2017, Vol. 27, No. 4: 593-594.


http://ift.tt/2nCqzeo

Predictors of hearing recovery in patients with severe sudden sensorineural hearing loss

Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient's social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not pre...

http://ift.tt/2oB68TF

The T4/T3 quotient as a risk factor for differentiated thyroid cancer: a case control study

The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid di...

http://ift.tt/2nI7J6v

Systemic therapy in the curative treatment of head and neck squamous cell cancer: a systematic review

To review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in...

http://ift.tt/2nI90dV

Recovery of Abnormal ABR in Neonates and Infants at Risk of Hearing Loss

The purpose of this retrospective study is to present the clinical experience of a single institution on the recovery of ABR thresholds in a large population of neonates and infants at risk of hearing loss. Potential prognostic factors associated with this phenomenon were also investigated. Out of 2248 high risk infants, 384 had abnormal ABR at initial hearing evaluation and 168 of them had absent ABR or a threshold ≥80 dBnHL. From this subgroup, a significant percentage showed complete or partial recovery on reexamination (32.7% and 9.3%, resp.), performed 4–6 months later. The presence of normal otoacoustic emissions was associated with the ABR restoration on reexamination. Moreover, the very young age at the initial hearing screening seems to be related to higher probabilities of false positive ABR. The potential recovery of hearing in HR infants raises concerns about the very early cochlear implantation in HR infants less than one year. Such a treatment modality should be decided cautiously and only after obtaining valid and stable objective and subjective hearing thresholds. This holds especially true for infants showing an auditory neuropathy profile, as they presented a much greater probability of ABR recovery.

http://ift.tt/2oxq5L4

Idiopathic atrophoderma of Pasini and Pierini: A case study of collagen and elastin texture by multiphoton microscopy

The diagnosis of idiopathic atrophoderma of Pasini and Pierini (IAPP) relies on typical clinical features, particularly distinctive pigmented ovular/round depressed plaques. Histologic examination often reveals no obvious changes, but patterns of collagen distribution, using multiphoton imaging and second harmonic generation can help track hidden details of tissue organization contributing to atrophy.

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Topical Drug Therapies for Chronic Rhinosinusitis

Chronic rhinosinusitis is recognized as an inflammatory syndrome involving the nose and paranasal sinuses of multifactorial etiology. Research has demonstrated a complex interplay between host factors, microbiota, environmental exposures, and epigenetics resulting in chronic mucosal inflammation. The mainstay of medical therapy addresses this inflammation. In previously operated sinuses this includes topical saline and corticosteroids, reserving antibiotics for culture-directed acute exacerbations. Topical antiinflammatory therapies allow increased local concentration of drugs while minimizing side effects. Topical therapies have advanced the surgical field by improving and maintaining postoperative outcomes. The topical therapies include saline, corticosteroids, antibiotics, and antifungals.

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Evolution in Visualization for Sinus and Skull Base Surgery

Rhinoscopy became a formal field of study in the mid-nineteenth century as improvements in nasal specula were made and the potent vasoconstrictive effects of cocaine on the intranasal tissues were discovered. Since then, a multitude of advances in visualization and illumination have been made. The advent of the Storz-Hopkins endoscope in the mid-twentieth century represents a culmination of efforts spanning nearly 2 centuries, and illumination has evolved concomitantly. The future of endoscopic sinus surgery may integrate developing technologies, such as 3-dimensional endoscopy, augmented reality navigation systems, and robotic endoscope holders.

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Features of sinonasal hemangioma: A retrospective study of 31 cases

Although hemangiomas are common lesions of the head and neck, sinonasal hemangiomas are rare. The purpose of this study was to analyze the clinical features (sex, age, symptoms, and size and anatomical location of the lesion) and the histological findings of sinonasal hemangioma cases, to assess preoperative transarterial embolization, and to evaluate the outcome (recurrence or no recurrence) of endoscopic sinus surgery.

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A case of extensive pharyngeal vascular malformation successfully treated with Kampo medicine

To present the efficacy of Japanese-traditional medicine (Kampo) for a case with vascular malformation.

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IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration

Summary

Background

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod", which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators.

Objective

Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin.

Methods

Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed.

Results

After 10 min in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 min, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase, previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin.

Conclusions and Clinical Relevance

Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate on periostin-rich extracellular matrix in the asthmatic airway in an ADAM8-dependent manner, making ADAM8 a possible therapeutic target.

This article is protected by copyright. All rights reserved.

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A randomized controlled phase II clinical trial comparing ONO-4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis

Abstract

Background

Prostaglandin D₂ (PGD₂) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.

Objective

This study aimed to evaluate the efficacy and safety of a novel PGD₂ receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR).

Methods

This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.

Results

Both ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study.

Conclusions

We demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).

This article is protected by copyright. All rights reserved.

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RNase 7 downregulates TH2 cytokine production by activated human T-cells

Abstract

Background

The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T-cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity immunoregulatory functions have been published for several AMPs. In this study we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T-cells.

Methods

Isolated human CD3+ T-cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T-cells and in polarised TH2 cells using skin derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.

Results

Treatment of activated human CD4+ T-cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T-cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T-cells with RNase7.

Conclusion

Our data indicate that RNase 7 has immunomodulatory functions on TH2-cells and decreases the production of TH2 cytokines in the skin

This article is protected by copyright. All rights reserved.

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Clinical laser treatment of toenail onychomycoses

Abstract

Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.

http://ift.tt/2nGqO9n

Magnetic resonance imaging predicts chronic dizziness after benign paroxysmal positional vertigo

We aimed to evaluate the clinical implications of magnetic resonance imaging (MRI) findings in patients with benign paroxysmal positional vertigo (BPPV).

http://ift.tt/2oG4woQ

Quantitative imaging analysis of transcanal endoscopic Infracochlear approach to the internal auditory canal

A transcanal endoscopic infracochlear surgical approach to the internal auditory canal in a human temporal bone model has been described. The proportion of patients with favorable anatomy for this novel surgical technique is unknown. Herein, we perform a quantitative analysis of the infracochlear corridor to the IAC based on computed tomography.

http://ift.tt/2oAA3LJ

Prognostic factors in head and neck mucosal malignant melanoma

Publication date: Available online 3 April 2017
Source:Auris Nasus Larynx
Author(s): Şenol Çomoğlu, Beldan Polat, Mehmet Çelik, Bayram Şahin, Necati Enver, Meryem Nesil Keleş, Şule Öztürk Sarı
ObjectivePrimary mucosal malignant melanoma of the head and neck (HN-PMMM) is an aggressive and uncommon neoplasm. Herein, we present a series of 33 patients and the results of treatment, and aimed to determine prognostic factors in HN-PMMM.MethodsPatients who were diagnosed as having HN-PMMM in our reference hospital, between 2005 and 2014 were evaluated. Thirty-three of these patients who had follow-up data were included. Surgical margin status was extracted from the original pathology reports. Archived materials were retrieved for the histopathologic findings: ulceration, necrosis, lymphovascular invasion, perineural invasion, pigmentation, and presence of an in situ component. Mitotic activity was evaluated using phosphohistone H3 (PHH3) immunohistochemical staining.ResultsWe found an association of PHH3 mitotic activity with overall survival in a univariate analysis and to our knowledge, this is the first report among the available case series of HN-PMMM to evaluate mitotic activity using immunohistochemical staining. We also investigated the relationship between multicentricity and locoregional recurrence, which the authors believe is also a first.ConclusionPHH3 mitotic activity can be used a prognostic factor for head and neck mucosal malignant melanoma.



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Regeneration of subcutaneous tissue-engineered mandibular condyle in nude mice

To explore the feasibility of regenerating mandibular condyles based on cartilage cell sheet with cell bone-phase scaffold compared with cell-biphasic scaffolds.

http://ift.tt/2ozi3Sk

Osteosynthesis of partial rib osteotomy in a miniature pig model using human standard-sized magnesium plate/screw systems: effect of cyclic deformation on implant integrity and bone healing

Magnesium alloys are candidates for resorbable material in bone fixation. However, the degradation and performance of osteosynthesis plate/screw systems in vivo, under cyclic deformation, is unknown. We evaluated the outcomes of human standard-sized magnesium plate/screw systems with or without plasma-electrolytic surface modifications in a miniature pig rib model. Of a total of 14 minipigs, six were implanted with coated magnesium WE43 six-hole plates/screws, six received magnesium uncoated plates/screws, and two received titanium osteosynthesis systems.

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Differenzialtherapie des fortgeschrittenen metastasierten kleinzelligen Lungenkarzinoms

Zusammenfassung

Hintergrund

Das aggressive biologische Verhalten des kleinzelligen Lungenkarzinoms (SCLC) im Sinne einer kurzen Tumorverdopplungszeit und frühen Metastasierungstendenz begründet, dass 70 % der Betroffenen bereits bei Erstdiagnose an einem fortgeschrittenen metastasierten Krankheitsstadium leiden. Die genetische Komplexität und Instabilität des SCLC sowie die frühe Selektion therapieresistenter Zelllinien bedingt eine ausgeprägte Neigung zu Rezidiven, liefert jedoch Ansatzpunkte für zielgerichtete Therapien. Insgesamt ist die Chemotherapie ein wesentliches Standbein der multimodalen und interdisziplinären Behandlung.

Material und Methoden

Die Arbeit basiert auf einer selektiven Literaturrecherche der Datenbanken PubMed und Cochrane zum Thema metastasiertes kleinzelliges Lungenkarzinom.

Ergebnisse und Schlussfolgerung

Das SCLC ist mit hohen Ansprechraten besonders chemotherapiesensibel. Die Standardtherapie in der Erstlinie stellt auch nach 25 Jahren noch die Platindoublette in Kombination mit Etoposid dar und erreicht ein Tumoransprechen von 60–70 % mit einer Komplettremissionsrate von über 30 %. Das Tumorrezidiv ist jedoch obligat. In der zweiten Therapielinie führt Topotecan zu einer Verlängerung des Überlebens und einer Verbesserung der Lebensqualität und kann äquieffektiv oral oder parenteral appliziert werden. Amrubicin und andere anthrazyklinhaltige Polychemotherapien stellen eine wirksame Therapiealternative in der Zweitlinie dar. In der Drittlinie gibt es keine validierten Strategien; häufig wird jedoch auf Kombinationen aus der Erstlinie oder Monotherapien zurückgegriffen. Die moderne zielgerichtete Tumortherapie hat bisher zu keiner etablierten Strategie geführt. Die frühzeitige Integration der supportiven und palliativmedizinischen Versorgung ist wesentlicher Bestandteil einer hohen Versorgungsqualität. Trotz differenzieller Ansätze und dem Einsatz zielgerichteter Therapien konnte in den letzten 30 Jahren kein nennenswerter Fortschritt in der Therapie der metastasierten Erkrankung erreicht werden.

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Epidemiologie des kleinzelligen Lungenkarzinoms in Deutschland

Zusammenfassung

Etwa jeder 5. bis 6. bösartige Tumor der Lunge, für den in den Krebsregistern spezifische histologische Angaben vorliegen, wird derzeit als kleinzelliges Lungenkarzinom (SCLC) diagnostiziert. In 2013 wurden bundesweit 7440 Neuerkrankungen erfasst, davon etwa 40 % bei Frauen. Der Anteil der SCLC ist zuletzt rückläufig, während derjenige der Adenokarzinome der Lunge − auch international − zunimmt. Die ungünstigere Verteilung der Tumorstadien gegenüber dem nichtkleinzelligen Lungenkarzinom (NSCLC) erklärt sich v. a. durch eine frühere Lymphknoten- und Fernmetastasierung; nur 5 % der SCLC werden in frühen Stadien (UICC I/II) diagnostiziert. Dies bedingt z. T. auch die mit einem relativen Fünfjahresüberleben von zuletzt 8,9 % (Frauen) bzw. 6,5 % (Männer) deutlich schlechtere Prognose im Vergleich zum NSCLC. Allerdings weisen auch bei vergleichbarem Tumorstadium Patienten mit SCLC etwas niedrigere Überlebensraten auf als solche mit NSCLC. Selbst über 3 Jahrzehnte zeigen sich anhand US-amerikanischer Daten nur geringe Verbesserungen in den Überlebensraten. Das SCLC gehört damit weiterhin zu den Malignomen mit der ungünstigsten Prognose.

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Psychoonkologische Versorgung von Patienten mit akuter Leukämie

Zusammenfassung

Die psychoonkologische Versorgung von Tumorpatienten ist in der onkologischen Medizin zunehmend etabliert, nicht zuletzt durch die Implementierung der S3-Leitlinie. Darüber hinaus gibt es bei der psychoonkologischen Versorgung von Patienten mit akuten Leukämien einige spezifische Besonderheiten zu berücksichtigen. In diesem Artikel werden Aspekte aufgezeigt, die Ärzte und Psychoonkologen bei der Unterstützung der Patienten beachten sollten.

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Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies

Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present f...

http://ift.tt/2nUCGFn

Sputum cell counts to manage prednisone-dependent asthma: effects on FEV1 and eosinophilic exacerbations

Prednisone dependence in asthma is usually described based on clinical and spirometric characteristics. It is generally believed that these patients have frequent exacerbations and lose lung function rapidly b...

http://ift.tt/2oyZwpj

Nasal nitric oxide in allergic rhinitis in children and its relationship to severity and treatment

Nasal nitrous oxide (nNO) is increased in allergic rhinitis (AR), but not in asthma, and is a non-invasive marker for inflammation in the nasal passages.

http://ift.tt/2o014HB

Consumer preferences for food allergen labeling

Food allergen labeling is an important tool to reduce risk of exposure and prevent anaphylaxis for individuals with food allergies. Health Canada released a Canadian food allergen labeling regulation (2008) an...

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Xylitol nasal irrigation in the treatment of chronic rhinosinusitis

Publication date: Available online 4 April 2017
Source:American Journal of Otolaryngology
Author(s): Lin Lin, Xinyue Tang, Jinjin Wei, Fei Dai, Guangbin Sun
ObjectiveTo evaluate the efficacy of xylitol nasal irrigation (XNI) treatment on chronic rhinosinusitis (CRS) and to investigate the effect of XNI on nasal nitric oxide (NO) and inducible nitric oxide synthase (iNOS) mRNA in maxillary sinus.Materials and methodsPatients with CRS were enrolled and symptoms were assessed by Visual Analog Scale (VAS) and Sino-Nasal Outcome Test 22 (SNOT-22). Nasal NO and iNOS mRNA in the right maxillary sinus were also examined. Then, they were treated with XNI (XNI group) or saline nasal irrigation (SNI, SNI group) for 30days, after which their symptoms were reassessed using VAS and SNOT-22, and nasal NO and iNOS mRNA in the right maxillary sinus were also reexamined.ResultsTwenty-five out of 30 patients completed this study. The scores of VAS and SNOT-22 were all reduced significantly after XNI treatment, but not after SNI. The concentrations of nasal NO and iNOS mRNA in the right maxillary sinus were increased significantly in XNI group. However, significant changes were not found after SNI treatment. Furthermore, there were statistical differences in the assessments of VAS and SNOT-22 and the contents of nasal NO and iNOS mRNA in the right maxillary sinus between two groups.ConclusionsXNI results in greater improvement of symptoms of CRS and greater enhancement of nasal NO and iNOS mRNA in maxillary sinus as compared to SNI.



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Quantitative imaging analysis of transcanal endoscopic Infracochlear approach to the internal auditory canal

Publication date: Available online 4 April 2017
Source:American Journal of Otolaryngology
Author(s): Judith Kempfle, Benjamin Fiorillo, Vivek V. Kanumuri, Samuel Barber, Albert Edge, Marybeth Cunnane, Aaron K. Remenschneider, Daniel J. Lee, Elliott D. Kozin
PurposeA transcanal endoscopic infracochlear surgical approach to the internal auditory canal in a human temporal bone model has been described. The proportion of patients with favorable anatomy for this novel surgical technique is unknown. Herein, we perform a quantitative analysis of the infracochlear corridor to the IAC based on computed tomography.Materials and methodsComputed tomography scans of adult temporal bones were measured to determine the accessibility of the IAC when using a transcanal, cochlear-sparing surgical corridor.ResultsThis approach to the IAC was feasible in 92% (35 of 38) specimens based on a minimum distance of 3mm between the basilar turn of the cochlear and the great vessels (jugular bulb and carotid artery).ConclusionsInfracochlear access to the IAC is feasible in the majority of adult temporal bones and has implications for future hearing preservation drug delivery approaches to the IAC.



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Magnetic resonance imaging predicts chronic dizziness after benign paroxysmal positional vertigo

Publication date: Available online 4 April 2017
Source:American Journal of Otolaryngology
Author(s): Wang Woon Cha, Kudamo Song, In Kyu Yu, Myoung Su Choi, Dong Sik Chang, Chin-Saeng Cho, Ho Yun Lee
ObjectivesWe aimed to evaluate the clinical implications of magnetic resonance imaging (MRI) findings in patients with benign paroxysmal positional vertigo (BPPV).MethodsA total of 120 patients diagnosed with BPPV completed MRI at the emergency room between December 2012 and June 2015 and met our criteria for inclusion in this study. Epidemiologic characteristics, the results of audio-vestibular testing, and MRI findings were retrospectively analyzed.ResultsThe most common findings were white matter hyperintensities (70.0%), sinusitis (34.2%), and brain atrophy (25.0%). There were no significant differences in MRI findings or epidemiologic characteristics according to BPPV subtype (p>0.05). A multiple regression analysis revealed that BPPV recurrence (odds ratio, 6.88; 95% confidence interval, 1.67–34.48; p=0.009) and brain atrophy (odds ratio, 4.39; 95% confidence interval, 1.11–21.28; p=0.036) were positively associated with dizziness lasting longer than 3months.ConclusionBrain atrophy was independently associated with long-lasting dizziness after BPPV. Although the mechanism is unclear, brain atrophy may have relevance to otoneurotologic disease-related changes in brain structure.



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The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective

Publication date: Available online 4 April 2017
Source:American Journal of Otolaryngology
Author(s): Ahmad I. Al Omari, Firas Q. Alzoubi, Mohammad M. Alsalem, Samah K. Aburahma, Diala T. Mardini, Paul F. Castellanos
IntroductionEpilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years.VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively.ObjectivesThis study is to review the outcomes of vagal nerve stimulator (VNS) implantation in terms of the surgical procedures, complications, seizure frequency, and the clinical effect on larynx and vocal folds motion.MethodsSeries of thirty consecutive patients who had VNS implantation between 2007 and 2014 were recruited. Seizure-frequency outcome, surgical complications and device adverse effects of VNS were retrospectively reviewed. Additional evaluation included use of the Voice Handicap Index and Maximum Phonation Time (MPT) were conducted before and after the implantation.Videolaryngoscopy was used to evaluate the vocal fold mobility before and after the VNS implantation.ResultsSeizure frequency reduction over a minimum of 2years of follow up demonstrated: 100% in seizure frequency reduction in 1 patient, drastic reduction in seizure frequency (70–90%) in 9 patients, a good reduction in terms of seizure frequency (50%) in 8 patients, a 30% reduction in 5 patients, no response in 6 patients, and 1 patient had increased frequency.The most commonly reported adverse effects after VNS activation were coughing and voice changes with pitch breaks, as well as mild intermittent shortness of breath in 33% of patients. For those patients secondary supraglottic muscle tension and hyper function with reduced left vocal fold mobility were noticed on videolaryngoscopy, though none had aspiration problems.Surgical complications included a wound dehiscence in one patient (3%) which was surgically managed, minor intra-operative bleeding 3%; a superficial wound infection in one patient (3%) which was treated conservatively, none of the complications necessitated VNS removal.ConclusionsVNS appears to be an effective non-pharmacologic adjuvant therapy in patients with medically refractory seizures. With the favorable adverse-effect profile previously described, VNS is generally well tolerated and of a great benefit to such patients.Laryngeal side effects, of which hoarseness being of the greatest repetition, are the most common after the VNS implantation. VNS can affect the voice and reduced vocal cord motion on the implantation side with secondary supraglottic muscle tension.Otolaryngologists are not only capable of performing VNS implantation, but can also manage surgical complications, assess laryngeal side effects and treat them as needed.



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Parallel antibody germline gene and haplotype analyses support the validity of immunoglobulin germline gene inference and discovery

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Ufuk Kirik, Lennart Greiff, Fredrik Levander, Mats Ohlin
Analysis of antibody repertoire development and specific antibody responses important for e.g. autoimmune conditions, allergy, and protection against disease is supported by high throughput sequencing and associated bioinformatics pipelines that describe the diversity of the encoded antibody variable domains. Proper assignment of sequences to germline genes are important for many such processes, for instance in the analysis of somatic hypermutation. Germline gene inference from antibody-encoding transcriptomes, by using tools such as TIgGER or IgDiscover, has a potential to enhance the quality of such analyses. These tools may also be used to identify germline genes not previously known. In this study, we exploited such software for germline gene inference and define aspects of analysis settings and pre-existing knowledge of germline genes that affect the outcome of gene inference. Furthermore, we demonstrate the capacity of IGHJ and IGHD haplotype inference, whenever subjects are heterozygous with respect to such genes, to lend support to IGHV gene inference in general, and to the identification of novel alleles presently not recognized by germline gene reference directories. We propose that such haplotype analysis shall, whenever possible, be used in future best practice to support the outcome of germline gene inference. IGHJ-directed haplotype inference was also used to identify haplotypes not expressing some IGHV germline genes. In particular, we identified a haplotype that did not express several major germline genes such as IGHV1-8, IGHV3-9, IGHV3-15, IGHV1-18, IGHV3-21, and IGHV3-23. We envisage that haplotype analysis will provide an efficient approach to identify subjects for further studies of the link between the available immunoglobulin repertoire and outcomes of immune responses.

Graphical abstract

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Editorial Board/ Publication Information

Publication date: May 2017
Source:Molecular Immunology, Volume 85





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Effective nasal mask ventilation of a difficult airway in a patient with advanced salivary gland cancer

We report a case of successful nasal mask ventilation in a patient with a difficult airway and advanced salivary cancer.

http://ift.tt/2ozIo2s

Use of the Laryngeal Mask Airway (LMA) Protector™ for shoulder surgeries in beach-chair position

The use of supraglottic airway devices in the management of airway for patients in beach-chair positions for shoulder surgeries is often appropriate and increasingly favoured over tracheal intubation due to the potential complications associated with the latter [1,2]. We report our initial experience and satisfactory performance of the Laryngeal Mask Airway (LMA) Protector™ in three patients scheduled for elective shoulder surgeries performed in beach-chair positions. Recently introduced in 2016, the LMA Protector™ is a single-use second-generation supraglottic airway device complete with a pharyngeal chamber and dual gastric access ports.

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The T4/T3 quotient as a risk factor for differentiated thyroid cancer: a case control study

Abstract

Background

The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid disease. This study set out to understand the relationship between the levels of fT4 and fT3 and differentiated thyroid cancer.

Methods

A case-control study was conducted with 142 cases and 86 controls from the McGill University Teaching Hospitals. All patients underwent thyroid surgery. Cases were defined as patients with malignant nodules confirmed on final pathology and controls were defined as patients with benign nodules. The serological levels of TSH, fT4 and fT3 were measured preoperatively. Odds ratios were determined for each parameter and logistic regressions were calculated between markers and probability of malignancy. Additionally, fT4 values were divided by fT3 values (fT4/fT3 quotient) for each patient and an odds ratio was calculated.

Results

Amongst cases, the mean TSH was 2.25 ± 0.360U/mL, fT4 was 14.8 ± 0.689pmol/L, and fT3 was 4.65 ± 0.463pmol/L. Amongst controls, the mean TSH was 2.36 ± 1.68U/mL, fT4 was 14.3 ± 1.71pmol/L, and fT3 was 5.27 ± 0.957pmol/L. Patients in the control group were more likely to have low TSH, while patients in the case group would have high fT4 and patients in the control group were more likely to have a low fT4. The OR for patients with TSH >4.4U/mL was 2.13 (0.97, 4.65), and for patients with TSH <0.4U/mL was 0.46 (0.22, 0.95). The OR for patients with fT4 > 16pmol/L was 2.10 (1.09, 4.06), and for patients with fT4 < 10pmol/L was 0.45 (0.20, 0.98). The OR for patients with fT3 > 5.5pmol/L was 0.39 (0.14, 1.28). The OR for patients with fT3 < 3pmol/L was 1.83 (0.25, 13.69). The average fT4/fT3 was 3.39 ± 0.206 for cases and 2.93 ± 0.467 for controls. The fT4/fT3 quotient was considered high if it was >3.3 (OR =6.00 (2.94, 12.25)).

Conclusion

In this study, a direct relationship between high levels of fT4 and malignancy was uncovered. Furthermore, low levels of TSH and fT4 increased the likelihood that a nodule was benign. In this study a fT4/fT3 ratio >3.3 increased the risk of malignancy by 3.6 times (p-value =0.0013).

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A large giant cell tumor of the larynx: case report and review of the literature

Abstract

Background

Giant cell tumors (GCTs) are typically found in the metaphyseal-epiphyseal area of long bones but can also occur in the head and neck region. GCT of the larynx is a rare entity with only 42 reported cases in the international literature. Furthermore, to the best of our knowledge this is the largest laryngeal GCT reported in the literature to date. GCT of the larynx can present with dysphonia, dyspnea, and/or dysphagia and should be considered in the differential diagnosis of a neck mass.

Case presentation

This case report describes a giant cell tumor of the left thyroid cartilage in a 30-year-old man who initially presented with dysphonia and dysphagia. Computed tomography (CT) revealed a 5 × 5.7 cm mass centered on the left thyroid cartilage, which was further diagnosed by histopathology as giant cell tumour by open biopsy. The patient was counselled on treatment options and it was decided to proceed with a surgical approach. The patient consented to and successfully underwent a total laryngectomy (TL). Currently the patient has no evidence of disease at 13 months follow-up, has an optimal prosthetic voice, and is able to tolerate all textures of foods.

Conclusion

GCTs of the larynx have a good prognosis and can be treated successfully through complete resection of the tumor, negating the need for adjunctive therapy such as radiation, chemo or denosumab therapy.

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The first Canadian experience with the Afirma® gene expression classifier test

Abstract

Background

Thyroid nodules are common and often benign, although prove to be malignant upon surgical pathology in 5–15% of cases. When assessed with ultrasound-guided fine-needle aspiration (USFNA), 15–30% of the nodules yield an indeterminate result. The Afirma® gene expression classifier (AGEC) was developed to improve management of indeterminate thyroid nodules (ITNs) by classifying them as "benign" or "suspicious." Objectives were (1) to assess the performance of the AGEC in two Canadian academic medical centres (2), to search for inter-institutional variation and (3) to compare AGEC performance in Canadian versus American institutions.

Methods

We undertook a retrospective cohort study of patients with indeterminate cytopathology (Bethesda Class III or IV) as per USFNA who underwent AGEC testing. We reviewed patient demographics, cytopathological results, AGEC data and, if the patient underwent surgery, results from their final pathology.

Results

In total, we included 172 patients with Bethesda Class III or IV thyroid nodules underwent AGEC testing, 109 in Montreal, Quebec and 63 in St. John's, Newfoundland, in this study. Among the nodules sent for testing, 55% (60/109) in Montreal and 46% (29/63) in St. John's returned as "benign." None of these patients underwent surgery. On the other hand, 45% (49/109) nodules in Montreal and 54% (34/63) in St. John's were found to be "suspicious," for a total of 83 specimens. Seventy seven of these patients underwent surgery. Both in Montreal and St. John's, the final pathology yielded malignant thyroid disease in approximately 50% of the specimens categorized as "suspicious." Since 2013, no patient diagnosed with a benign nodule as per AGEC testing was found to harbor a malignant thyroid nodule on follow-up.

Conclusions

Molecular analysis is increasingly used in the management of indeterminate thyroid nodules. This study highlights the experience of two Canadian centres with AGEC testing. We found inter-institutional variability in the rate of nodules returning as "benign," however we found similar rates of confirmed malignancy in nodules returning as "suspicious." According the literature, results for AGEC testing in two Canadian institutions align with results reported in American centres.

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Predictors of hearing recovery in patients with severe sudden sensorineural hearing loss

Abstract

Background

Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient's social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not predictable.

Methods

We conducted a retrospective study in order to identify parameters that influence hearing recovery. The data base contains results of basic otoneurological tests and clinical parameters of 198 patients with idiopathic SSHL of at least 60 dB in at least four frequencies, diagnosed and treated at the University Hospital of Münster, Germany, between 1999 and 2015. Hearing recovery was measured by pure tone audiometry.

Results

Multivariate linear and logistic regression analyses indicate that the chance as well as the magnitude of hearing recovery is higher for patients with normal caloric testing than for patients with pathological caloric testing. However, for the subgroup of patients who attained a hearing recovery, the caloric testing result was not found to influence the magnitude. Instead, the magnitude was noticeably lower for patients within this subgroup who had a previous hearing loss. Furthermore, we found indications that the magnitude is higher for men than for women and that receiving a high-dose steroid therapy is associated with a higher chance and magnitude of a hearing recovery.

Conclusions

We conclude that SSHL associated with disorders of the vestibular system or previous hearing loss represent special sub-entities of SSHL that may be caused by unique pathophysiological mechanisms and are associated with worse outcome. Furthermore, our data support the importance of elevated dosage of steroids in SSHL therapy.

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Systemic therapy in the curative treatment of head and neck squamous cell cancer: a systematic review

Abstract

Objective

To review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in patients with locally advanced nonmetastatic (Stage III to IVB) squamous cell carcinoma of the head and neck (LASCCHN).

Method

Recognizing the Meta-analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) group reports have de facto guided practice since 2000, we searched for systematic reviews in the MEDLINE, EMBASE and Cochrane Database of Systematic Reviews published from January 2000 to February 2015 in reference to 4 research questions. A search was also conducted for randomized trials (RCTs) up to February 2015 not included in the meta-analyses.

Result

The MACH-NC reports, 5 additional meta-analyses, and 30 RCTs not included by MACH-NC were identified. For chemotherapy, MACH-NC findings showing improved overall survival with concomitant chemoRT did not require modification. High-dose cisplatin was most commonly studied. We confirmed this benefit with cisplatin monotherapy in patients treated with with postoperative concurrent chemoRT. Other than cetuximab, no targeted agents and radiosensitizers studied in RCTs were shown effective. TPF induction chemotherapy was superior to PF for tumor response and larynx preservation but not survival. Larynx preservation was reported with both CRT and induction chemotherapy approaches.

Conclusion

ChemoRT with cisplatin at least 40 mg/m2 per week given as radical or postoperative adjuvant remains a standard treatment approach for LASCCHN that improves overall survival but increases toxicity. 5-FU plus platinum is supported by less data but may be a reasonable alternative for patients unsuitable for cisplatin. Of note, stratification of outcomes by HPV-status was not available but outcomes for oropharynx cancer appeared similar to other subsites in chemoRT RCTs. No RCTs have yet demonstrated superiority or non-inferiority of cetuximab-RT to CRT. In view of this, cetuximab-RT is suggested only for patients not candidates for CRT. Taxane-based triplet induction chemotherapy is superior to doublets for rapid tumour downsizing and for larynx preservation, but does not improve overall survival and should be used with primary G-CSF prophylaxis. Further investigation of induction approaches for larynx preservation may be warranted.

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Assessment of Depression, Anxiety, Quality of Life, and Coping in Long-Standing Multiple Endocrine Neoplasia Type 2 Patients

Thyroid , Vol. 0, No. 0.


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Study of SHR-1210 Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal Cancer

Condition:   Esophageal Carcinoma
Interventions:   Biological: SHR-1210;   Drug: Docetaxel;   Drug: Irinotecan
Sponsor:   Jiangsu HengRui Medicine Co., Ltd.
Not yet recruiting - verified February 2017

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Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

Condition:   Metastatic Thyroid Cancer
Interventions:   Drug: Cyclophosphamide;   Drug: Sirolimus
Sponsor:   University of Michigan Cancer Center
Not yet recruiting - verified March 2017

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Selected Literature Watch

Violence and Gender , Vol. 0, No. 0.


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Tongue surgeries for pediatric obstructive sleep apnea: a systematic review and meta-analysis

Abstract

Objectives

To evaluate the international literature for studies reporting outcomes for obstructive sleep apnea (OSA) in children undergoing isolated tongue surgeries.

Methods

Two authors searched from inception through November 14, 2016 in four databases including PubMed/MEDLINE.

Results

351 studies were screened. Eleven studies (116 children) met criteria. Most children were syndromic and had craniofacial disorders, co-morbidities, or other serious medical issues. Surgeries included base-of-tongue (BOT) reduction (n = 114), tongue suspension (n = 1), and hypoglossal nerve stimulation (n = 1). The pre- and post-BOT reduction surgeries decreased apnea–hypopnea index (AHI) from a mean (M) and standard deviation (SD) of 16.9 ± 12.2/h to 8.7 ± 10.6/h (48.5% reduction) in 114 patients. Random effects modeling (109 patients) demonstrated a standardized mean difference for AHI of −0.78 (large magnitude of effect) [95% CI −1.06, −0.51], p value <0.00001. For BOT surgery in 53 non-syndromic children, the AHI decreased 59.2% from 14.0 ± 11.4 to 5.7 ± 6.7/h, while in 55 syndromic children, the AHI decreased 40.0% from 20.5 ± 19.1 to 12.3 ± 18.2/h. BOT reduction improved lowest oxygen saturation from M ± SD of 84.7 ± 7.4–87.9 ± 6.5% in 113 patients. Hypoglossal nerve stimulation and tongue-base suspension are limited to case reports.

Conclusions

Most children undergoing tongue surgeries in the literature were syndromic and had craniofacial disorders, co-morbidities, or other serious medical issues. Children with a body mass index <25 kg/m² and non-syndromic children have had the most improvement in AHI. The specific type of surgery must be tailored to the patient. Patients with co-morbidities should undergo treatment in centers that are equipped to provide appropriate perioperative care.

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Surgical site infection: clean surgery and antimicrobials

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Feasibility, reliability, and validity of the Japanese version of the 12-item World Health Organization Disability Assessment Schedule-2 in preoperative patients

Abstract

Purpose

The avoidance of postoperative functional disability is one of the most important concerns of patients facing surgery, but methods to evaluate disability have not been definitively established. The aim of our study was to evaluate the feasibility, reliability, and validity of the Japanese version of the 12-item World Health Organization Disability Assessment Schedule-2 (WHODAS 2.0-J) in preoperative patients.

Methods

Individuals aged ≥55 years who were scheduled to undergo surgery in a tertiary-care hospital in Japan between April 2016 and September 2016 were eligible for enrolment in the study. All patients were assessed preoperatively using the WHODAS 2.0-J, the 8-Item Short Form (SF-8) questionnaire, and the Tokyo Metropolitan Institute of Gerontology Index (TMIG Index). The feasibility, reliability, and validity of WHODAS2.0-J were evaluated using response rate, Cronbach's alpha (a measure of reliability), and the correlation between the WHODAS 2.0-J and the SF-8 questionnaire and TMIG Index, respectively.

Results

A total of 934 patients were enrolled in the study during the study period, of whom 930 completed the WHODAS 2.0-J (response rate 99.5%) preoperatively. Reliability and validity were assessed in the 898 patients who completed all three assessment tools (WHODAS 2.0-J, SF-8 questionnaire, and TMIG Index) and for whom all demographic data were available. Cronbach's alpha was 0.92. The total score of the WHODAS 2.0-J showed a mild or moderate correlation with the SF-8 questionnaire and TMIG Index (r = −0.63 to −0.34).

Conclusion

The WHODAS 2.0-J is a feasible, reliable, and valid instrument for evaluating preoperative functional disability in surgical patients.

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AhR mediates an anti-inflammatory feed-back mechanism in human Langerhans cells involving FcεRI and IDO

Abstract

Background

Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of atopic dermatitis (AD) patients carry the high affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes.

Objectives

We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro generated LC.

Methods

Epidermal cells from healthy skin were analyzed for their expression of AhR and AhRR. LC generated from CD34⁺ hematopoietic stem cells (CD34LC) were treated with the UV photoproduct and AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ). Cell surface receptors, transcription factors and the tolerogenic tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) were analyzed using flow cytometry and quantitative PCR.

Results

Epidermal LC and CD34LC express AhR and AhRR. AhR was also found in keratinocytes, which lack AhRR. AhR activation of LC by FICZ caused down-regulation of FcεRI in CD34LC without affecting their maturation. AhR-mediated regulation of FcεRI did not involve any known transcription factors related to this receptor. Furthermore, we could show up-regulation of IDO mediated by AhR engagement.

Conclusions

Our study shows that AhR activation by FICZ reduces FcεRI and up-regulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD.

This article is protected by copyright. All rights reserved.

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Tissue regeneration in dentistry: can salamanders provide insight?

Abstract

The ability to regenerate damaged tissues would be of tremendous benefit for medicine and dentistry. Unfortunately, humans are unable to regenerate tissues such teeth, fingers or to repair injured spinal cord. With an aging population, health problems are more prominent and dentistry is no exception as loss of bone tissue in the orofacial sphere from periodontal disease is on the rise. Humans can repair oral soft tissues exceptionally well, however hard tissues, like bone and teeth, are devoid of the ability to repair well or at all. Fortunately, Mother Nature has solved nearly every problem that we would like to solve for our own benefit and tissue regeneration is no exception. By studying animals that can regenerate, like Axolotls (Mexican salamander), we hope to find ways to stimulate regeneration in humans. We will discuss the role of the transforming growth factor beta cytokines as they are central to wound healing in humans and regeneration in Axolotls. We will also compare wound healing in humans (skin and oral mucosa) to Axolotl skin wound healing and limb regeneration. Finally, we will address the problem of bone regeneration and present results in salamanders which indicate that in order to regenerate bone you need to recruit non-bone cells. Fundamental research, such as the work being done in animals that can regenerate, offers insight to help understand why some treatments are successful while others fail when it comes to specific tissues such as bones.

This article is protected by copyright. All rights reserved.

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Bone marrow myeloid cells in regulation of multiple myeloma progression

Abstract

Survival, growth, and response to chemotherapy of cancer cells depends strongly on the interaction of cancer cells with the tumor microenvironment. In multiple myeloma, a cancer of plasma cells that localizes preferentially in the bone marrow, the microenvironment is highly enriched with myeloid cells. The majority of myeloid cells are represented by mature and immature neutrophils. The contribution of the different myeloid cell populations to tumor progression and chemoresistance in multiple myeloma is discussed.

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Changes in gustatory function in patients with chronic otitis media before and after tympanoplasty

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Regeneration of subcutaneous tissue-engineered mandibular condyle in nude mice

Publication date: Available online 4 April 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Feiyu Wang, Yihui Hu, Dongmei He, Guangdong Zhou, Xiujuan Yang, Edward Ellis
PurposeTo explore the feasibility of regenerating mandibular condyles based on cartilage cell sheet with cell bone-phase scaffold compared with cell-biphasic scaffolds.Materials and MethodsTissue-engineered mandibular condyles were regenerated by the following: 1) cartilage cell sheet+bone-phase scaffold (PCL/HA) seeded with bone marrow stem cells (BMSCs) from minipigs (cell sheet group), and 2) cartilage phase scaffold (PGA/PLA) seeded with auricular chondrocytes + bone-phase scaffold seeded with BMSCs from minipigs (biphasic scaffold group). They were implanted subcutaneously in nude mice after being cultured in vitro for different periods of time. After 12 weeks, the mice were sacrificed, and the specimens were harvested and evaluated based on gross appearance and histopathologic observations with hematoxylin and eosin, safranin O-fast green and immumohistochemical staining for collagen I and II. The histopathologic assessment score of condylar cartilage and bone density were compared between the 2 groups using SPSS 17.0 software.ResultsThe 2 groups' specimens all formed mature cartilage-like tissues with numerous chondrocytes, typical cartilage lacuna and abundant cartilage-specific extracellular matrix. The regenerated cartilage was instant, continuous, homogeneous and avascular. In the biphasic scaffold group, there were still a few residual PGA fibers in the cartilage layer. The cartilage and bone interface was established in the 2 groups, and the microchannels of the bone-phase scaffolds were filled with bone tissue. The score of cartilage regeneration in the cell sheet group was a little higher than that in the biphasic scaffold group, but the difference was not significant (p>0.05). There was no significant difference in bone tissue formation between the 2 groups (p>0.05).ConclusionBoth the cartilage cell sheet group and the biphasic scaffold group of nude mice underwent regeneration of condyle-shaped osteochondral composite. Without residual PGA fibers, the cell sheet group might have less chance of immunological rejection compared to biphasic scaffold group.



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Osteosynthesis of partial rib osteotomy in a miniature pig model using human standard-sized magnesium plate/screw systems: effect of cyclic deformation on implant integrity and bone healing

Publication date: Available online 4 April 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Benoit Schaller, Nikola Saulacic, Stefan Beck, Thomas Imwinkelried, Edwin Wei Yang Liu, Ken Nakahara, Willy Hofstetter, Tateyuki Iizuka
Magnesium alloys are candidates for resorbable material in bone fixation. However, the degradation and performance of osteosynthesis plate/screw systems in vivo, under cyclic deformation, is unknown. We evaluated the outcomes of human standard-sized magnesium plate/screw systems with or without plasma-electrolytic surface modifications in a miniature pig rib model. Of a total of 14 minipigs, six were implanted with coated magnesium WE43 six-hole plates/screws, six received magnesium uncoated plates/screws, and two received titanium osteosynthesis systems.The performance of the plate/screw fixation system on partially osteotomized 7th ribs was compared with that on intact 9th ribs. Radiological examinations were performed in vivo at 1, 4 and 8 weeks and after euthanasia at 12 and 24 weeks. After euthanasia the bone blocks were analyzed by computed tomography (CT), microfocus computed tomography (micro-CT), histology and histomorphometry. Follow-up post-surgery showed no trouble with wound healing. In vivo radiological examinations showed higher amounts of gas formation above the uncoated magnesium plates fixed on the partially osteotomized and intact ribs. CT scans showed no broken plates or implant displacement. The micro-CT examination demonstrated better surrounding bone properties around the coated than the uncoated magnesium implants 12 weeks after surgery. No negative influence of magnesium degradation on bone healing was observed with histological examinations. Plastic deformation during surgery and cyclic deformation did not affect the integrity of the used magnesium plates. This study showed promising results for the further development of coated magnesium plate/screw systems for bone fixation.



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Severe Murine Typhus Presenting with Acalculous Cholecystitis: A Case Report and Literature Review

A 54-year-old otherwise healthy male, who was being evaluated for prolonged fever, developed clinical and ultrasonographic signs compatible with acute acalculous cholecystitis. Diagnosis of murine typhus was confirmed by serology and the patient was treated with doxycycline. He improved rapidly and all clinical and laboratory abnormalities returned to normal. The present case dictates that knowledge of the local epidemiology and keeping a high index of clinical suspicion can help recognize uncommon manifestations of murine typhus, in order to treat appropriately and avoid unnecessary investigations and interventions.

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Optimal timing for nasal fracture manipulation - is a two week target really necessary? A single-centre retrospective analysis of 50 patients

Abstract

Nasal bone fractures represent the most common isolated facial fracture and are involved in as many as 50% of facial fractures ⁽¹⁾. Its relative prominence in the centre of the face as well as its relatively thin, fragile structures makes it particularly susceptible to injury. Acute management is centred on restoring an aesthetically acceptable external nose with minimal airflow limitation. Conventional UK management typically involves assessment 5-7 days following injury, followed by closed reduction within two weeks, to avoid problems associated with fracture healing and bone remodelling ⁽²⁾.

This article is protected by copyright. All rights reserved.

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Reliability of Eustachian tube function measurements in a hypobaric and hyperbaric pressure chamber

Abstract

Objectives

Measurement of the Eustachian tube (ET) function is a challenge. The demand for a precise and meaningful diagnostic tool increases – especially since more and more operative therapies are being offered without objective evidence. The measurement of the ET function by continuous impedance recording in a pressure chamber is an established method, although the reliability of the measurements is still unclear.

Methods

25 participants (50 ears) were exposed to phases of compression and decompression in a hypo and hyperbaric pressure chamber. The ET function reflecting parameters – ET opening pressure (ETOP), ET opening duration (ETOD), and ET opening frequency (ETOF) – were determined under exactly the same preconditions three times in a row. The intraclass correlation coefficient (ICC) and Bland and Altman plot were used to assess test-retest reliability.

Results

ICCs revealed a high correlation for ETOP and ETOF in phases of decompression (passive equalisation) as well as ETOD and ETOP in phases of compression (active induced equalisation). Very high correlation could be shown for ETOD in decompression and ETOF in compression phases. The Bland and Altmann graphs could show that measurements provide results within a 95 % confidence interval in compression and decompression phases.

Conclusions

We conclude that measurements in a pressure chamber are a very valuable tool in terms of estimating the ET opening and closing function. Measurements show some variance comparing participants, but provide reliable results within a 95 % confidence interval in retest. This study is the basis for enabling efficacy measurements of ET treatment modalities.

This article is protected by copyright. All rights reserved.

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The MiRa scale, a new standardised scale for evaluating nasal deformities before and after septorhinoplasty: a prospective study comparing patient satisfaction and the surgeon's assessment

Summary

Objectives

The objective was to assess the reliability of a new standardised scale for evaluating nasal anomalies in order to compare the surgeon's assessment and patient satisfaction.

Design

Monocentric prospective cohort study.

Settings

First, we validated the reliability of the MiRa scale; then, we compared the surgeon's assessment and patient satisfaction.

Participants

Fifty-two patients underwent septorhinoplasty surgery and gave their written consent before inclusion.

Main outcome measurements

Primary outcome measurement was to validate the reliability of the MiRa scale: 2 observers analysed all records twice. Intra- and inter-observer reproducibility were evaluated using the intraclass correlation coefficient (ICC). Secondary outcome measurement was to compare the surgeon's assessment and patient satisfaction: MiRa and ROE (Rhinoplasty Outcome Evaluation) scores were established for each patient prior to and 6 months after surgery.

Results

Using the MiRa scale, ICC for intra- and inter-observer reproducibility were, respectively, 95.4% and 96%, showing no statistical difference (p=0.70, p=0.45). Good correlation scores were, respectively, 93% and 92%. Mean ROE scores were 7.1/24 (SD=11.3) before and 19.3/24 (SD=17.3) after surgery (p<0.05). We found an increase in MiRa and ROE scores of +19.75% and +51.25% (p<0.05), respectively. The average postoperative ROE score in the primary septorhinoplasty group was 20.4 (SD=14.4) and 17.2 (SD=23.1) in the secondary septorhinoplasty group (p<0.05).

Conclusion

MiRa scale is a reliable, standardised tool to evaluate surgical outcome in septorhinoplasty surgery. It provides an objective and reproducible score. The surgeon's assessment was more critical than patient satisfaction. Patient satisfaction is more difficult to achieve in cases involving a secondary septorhinoplasty.

This article is protected by copyright. All rights reserved.

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Carotid jugular fistula after Le Fort I osteotomy

Publication date: Available online 3 April 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): P.R. Osborne, T.F.V. Sverzut, A.E. Trivellato, C.M. Matias, C.E. Sverzut, A.T. Sverzut
Le Fort I osteotomy is the technique most applied worldwide in the treatment of dentoskeletal deformity involving the maxilla. Even though it is considered a very safe technique with good intra- and postoperative results, many complications have been described. This paper presents a case of carotid jugular fistula developed in a 22-year-old white male submitted to Le Fort I osteotomy for the treatment of anteroposterior maxillary deficiency, and discusses the possible aetiology and management of this serious complication.



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A Randomised Controlled Trial to evaluate the effect of a new skin care regimen on skin barrier function in those with podoconiosis in Ethiopia

Abstract

Background

Podoconiosis affects an estimated 3 million people in Ethiopia with a further 19 million at risk. Volcanic soil and pathogens enter skin breaches in the feet causing inflammation, lymphoedema and hyperkeratosis. There is no robust evidence on optimal podoconiosis skin care regimens to improve SBF.

Objectives

To evaluate the effectiveness of a new, low-cost, evidence-based intervention to improve SBF in the lower limbs of those with podoconiosis.

Methods

A randomized control trial (RCT) was conducted over 3 months in two podoconiosis clinics (n=193). The intervention comprised 2% glycerine (v/v) added to a reduced amount of soaking water. The control group received the current skin care regimen. Primary outcome measures were trans-epidermal water loss (TEWL) and stratum corneum hydration (SCH) at four specific sites on the lower limbs.

Results

Improvement in SBF was observed in both groups across all measurement sites and time points, although this was significantly greater in the experimental group. TEWL reduced in both groups at all sites. For example, on top of the foot the estimated group difference in TEWL at the fourth visit was 1.751 (SE=0.0390) in favour of the experimental group (t=3.154, df=189.580, p=0.002, 95% CI (0.0656 to 2.846)), indicating a greater reduction in the experimental group. Similarly, at the same site the estimated group difference in SCH at the fourth visit was -2.041(CI=0.572) in favour of the experimental group (t=-3.565, df=186.739, p=<0.001), 95% CI (-3.168 to -0.911)), indicating a greater increase in the experimental group. There were also significantly greater reductions in odour, number of wounds and largest foot circumference in the experimental compared to the control group.

Conclusions

The addition of 2% glycerine (v/v) to a reduced volume (83% reduction) of soaking water significantly improved SBF (Registered trial NCT02839772)

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Burnout in Dermatology Residents: a Canadian Perspective

Abstract

Burnout is a syndrome comprised of emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). It is associated with poor outcomes involving job performance and health.¹ Previous studies have reported burnout rates ranging from 18-84% during post-graduate medical education (i.e., residency); however, none have focused on dermatology residents (i.e., registrars, trainees).

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Herpes Simplex Proctitis Mimicking Inflammatory Bowel Disease in a Teenaged Male

We report the case of a 17-year-old male who was initially assessed for pain with defecation, bloody rectal discharge, and diarrhea, consistent with proctitis. Though proctitis is most commonly due to inflammatory bowel disease (IBD), infectious etiologies must also be considered, including sexually transmitted causes of infectious proctitis. In discussion of his sexual history, he identified as homosexual and acknowledged engaging in receptive anal intercourse. Rectal biopsies obtained via colonoscopy were culture-positive for herpes simplex virus (HSV), leading to a diagnosis of HSV proctitis and treatment with an appropriate antiviral medication. HSV proctitis is more common in individuals with high-risk sexual practices, including men who have sex with men. While this may be an uncommon diagnosis for pediatricians to make in practice, a high clinical index of suspicion for sexually transmitted infectious proctitis in those with risk factors must be maintained in order to facilitate appropriate testing, treatment, and counseling of affected individuals.

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Refined Internal Limiting Membrane Inverted Flap Technique for Intractable Macular Detachment with Optic Disc Pit

Purpose: To report a surgical technique for retinal detachment associated with optic disc pit (ODP) by using an internal limiting membrane (ILM) inverted flap as an obstacle between the vitreous cavity and subretinal space. Case Presentation: A 43-year-old man presented with decreased visual acuity in the right eye for 1 week due to macular detachment associated with ODP. After 2 unsuccessful surgeries, the retina was reattached by vitrectomy with an ILM inverted flap onto the ODP. Conclusion: Covering the pit with an inverted ILM flap is a reliable method for intercepting fluid from the vitreous cavity. Immediate absorption of subretinal fluid may lead to early macular attachment. This technique would be effective in managing ODP.
Case Rep Ophthalmol 2017;8:208–213

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Cortical auditory evoked potentials in children who stutter

Publication date: Available online 3 April 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Naema Ismail, Yossra Sallam, Reda Behery, Ameera Al Boghdady
IntroductionIt has been hypothesized that impaired auditory processing influence the occurrence of stuttering. Also, it is suggested that speech perception in children who stutter differed from normal. Auditory processing should be investigated in children who stutter shortly after the onset of stuttering in order to evaluate the extent to which impaired auditory processing contributes to the development of stuttering. CAEPs provide the necessary temporal and spatial resolution to detect differences in auditory processing and the neural activity that is related or time-locked to the auditory stimulus. The primary goal of the present study was to determine the difference in latency and amplitude of P1-N2 complex between children who stutter and non-stuttering children in response to speech stimuli.Material & MethodsThis case-control study was performed over 60 children, 30 were non-stuttering children (control group) and 30 were children who stutter (study group) ranging in severity from Bloodstien I to Bloodstien IV in the age range of 8-18 years.ResultsCAEPs of children who stutter with stuttering severity Bloodstien IV showed significant prolonged latencies and reduced amplitudes when blocks and IPDs were the most predominant core behaviors. P1 and N1 were prolonged in concomitant behaviors.ConclusionIt could be speculated that speech processing was affected in children who stutter with stuttering severity Bloodstien IV at the level of early perceptual auditory cortex.



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Ultrasound-guided thoracic paravertebral block by the paralaminar in-plane approach using a microconvex array transducer: methodological utility based on anatomical structures

Abstract

Objective

We evaluated the analgesic feasibility of paralaminar in-plane (PL) approach for ultrasound-guided thoracic paravertebral block (USG-TPVB). As the needle trajectory was expected to be closely affected by the distance from the skin to the lamina-transverse process junction (LTPJ), we examined the correlativity between them on computed tomography (CT) or ultrasonography.

Methods

Thirty-two patients undergoing thoracotomy were recruited. We measured the distances between the skin and LTPJ using preoperative CT (S-L) and procedural ultrasonography (US-L). At the beginning and the end of the surgery, 20 ml of 0.5% ropivacaine was injected. The level of sensory block and postoperative numerical pain rating scale (NRS) was assessed. Relationships among the measured parameters and the agreement of the needle depth (ND) with S-L and US-L were evaluated using Pearson's correlation coefficient and Bland–Altman analysis.

Results

S-L and US-L were strongly correlated with ND (r = 0.72 and r = 0.81, respectively) but not with BMI. The Bland–Altman analysis showed that the mean percent differences between the ND and S-L or ND and US-L were −9.6 and 20.1%, respectively. Catheters were inserted 18.6 mm lateral from the midline on average. Analgesia extended to 3–5 dermatomes in 29 patients, and the median NRS was 2 at 1, 6, 12, and 24 h after surgery, respectively.

Conclusions

We demonstrated that PL approach provided feasible analgesia for thoracotomy and the ND was significantly correlated with the morphometric values. This technique allowed for inner catheter insertion route targeting longer anteroposterior thoracic paravertebral space length; this may reduce potential risk of pleural puncture for USG-TPVB.

Trial registry number This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR). (URL:http://umin.ac.jp/ctr/, ID:UMIN000014821).

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Factors associated with the presence of postoperative headache in elective surgery patients: a prospective single center cohort study

Abstract

Purpose

Headache is an important cause of minor postoperative morbidity. In this study we evaluated the association of anesthesia and surgery with the occurrence of postoperative headache in elective surgery patients.

Methods

After obtaining ethical approval, 446 patients were enrolled in this prospective, single-centre cohort study. Participants were interviewed preoperatively, and for five days postoperatively, regarding the appearance of headache, while demographics, lifestyle, type of anesthesia and surgery, the anesthetic drugs administered and intraoperative adverse effects were recorded. Multiple logistic regression analysis was conducted in order to identify independent factors associated with postoperative headache, both in the total sample and in patients without previous history of headache.

Results

The observed overall frequency of postoperative headache was 28.3% (N = 126) in the total sample. In patients with previous history of headache, the frequency of postoperative headache was 41% (N = 89), while in those with no history the frequency of postoperative headache was 16.2% (N = 37). Female gender [p = 0.024; odds ratio (OR) = 2.1], sevoflurane administration (p < 0.001; OR = 3.66), intraoperative hypotension (p = 0.008; OR = 2.12) and smoking (p = 0.006; OR = 1.74) were independently associated with postoperative headache. In patients without previous history, female gender (p = 0.005; OR = 4.77), sevoflurane administration (p = 0.001; OR = 6.9), intraoperative hypotension (p = 0.006; OR = 6.7) and caffeine consumption (p = 0.041; OR = 5.28) presented greater likelihood for postoperative headache, while smoking revealed no association.

Conclusion

Female gender, sevoflurane, smoking and intraoperative hypotension were documented as independent risk factors for postoperative headache. In patients with no previous history of headache, caffeine consumption was an additional independent factor for postoperative headache, while smoking revealed no association.

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Intrathecal morphine versus intravenous opioid administration to impact postoperative analgesia in hepato-pancreatic surgery: a randomized controlled trial

Abstract

Purpose

Inadequate analgesia following abdominal surgery may affect outcome. Data in patients undergoing liver surgery suggested that postoperative coagulopathy might delay epidural catheter removal. Thus, alternative analgesic techniques should be evaluated.

Methods

We compared the analgesic efficacy of intraoperative intrathecal morphine [single injection 4 µg/kg before skin incision (ITM group, n = 23)] to intravenous opioids [iv remifentanil infusion during surgery followed by i.v. bolus of morphine, 0.15 mg/kg before the end of surgery (IVO group, n = 26)]. Forty-nine adult patients undergoing elective open resection of liver or pancreas lesions in the Tel Aviv Medical Center were randomized into the two analgesic protocols. Postoperatively both groups received i.v. morphine via a patient-controlled analgesia pump. Follow-up was till the 3rd postoperative day (POD).

Results

There was no significant difference in demographics and intraoperative data between groups. The primary outcome, pain scores on movement, was significantly worse in the IVO group when compared with the ITM group at various time points till POD3. In the secondary outcomes — need for rescue drugs — the IVO group required significantly more rescue morphine boluses. Complication related to the analgesia and recovery parameters were similar between groups.

Conclusions

The findings suggest that a single dose of ITM before hepatic/pancreatic surgery may offer better postoperative pain control than i.v. opioid administration during surgery. This beneficial effect is maintained throughout the first three PODs and is not associated with a higher complication rate; neither did it influence recovery parameters. ITM provides an appropriate alternative to i.v. morphine during major abdominal surgery.

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The protective effect of human atrial natriuretic peptide on renal damage during cardiac surgery

Abstract

Purpose

Acute kidney injury (AKI) is one of the critical complications after cardiac surgery. In the kidney, angiotensin II (Ang II) is formed by independent mechanisms, and activity of the intrarenal renin–angiotensin–aldosterone (RAAS) system contributes to the progression of kidney damage. Although atrial natriuretic peptide (ANP) exerts protective effects against renal injury by inhibiting the RAAS, the mechanisms of this effect have not been completely clarified. We investigated how human ANP (hANP) could prevent renal damage induced by cardiopulmonary bypass.

Methods

Forty-eight patients undergoing cardiac surgery were divided into two groups, with and without hANP infusion. Urinary angiotensinogen, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) were measured during and after surgery in both groups. Plasma renin activity, Ang II, aldosterone and serum creatinine were also measured.

Results

Urinary angiotensinogen levels in the hANP group were significantly lower than in the non-hANP group after cardiopulmonary bypass surgery, at the end of surgery and 3 h after surgery. At 3 h after surgery, urinary NGAL levels in the hANP and non-hANP groups were 371.1 ± 413.6 and 761.4 ± 437.8 μg/gCr, respectively (p < 0.01). Urinary L-FABP levels at the end of surgery in the hANP and non-hANP groups were 238.8 ± 107.4 and 573.9 ± 370.1 μg/gCr, respectively (p < 0.01). Moreover, hANP seemed to significantly reduce the incidence of postoperative AKI.

Conclusions

hANP demonstrated renal protective effects during cardiac surgery, and could possibly reduce the incidence of AKI after ischemia–reperfusion surgery. Moreover, this protective effect of hANP is likely induced by inhibition of the intrarenal RAAS.

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Comparison cisplatin with cisplatin plus 5FU in head and neck cancer patients received postoperative chemoradiotherapy

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Chien-Chih Chen, Jin-Ching Lin, Kuan-Wen Chen
PurposeTo compare the treatment outcomes and toxicity of both cisplatin and cisplatin plus 5FU chemotherapy in head and neck cancer patients who have received surgery, in addition to postoperative chemoradiotherapy.Materials and methodsFrom May 1991 to December 2012, a total of 113 head and neck cancer patients who received surgery, along with postoperative chemoradiotherapy were analyzed. The primary sites were oral cavity (86), oropharynx (17), hypopharynx (4), and larynx (6). Thirty-nine patients received cisplatin (P), while 74 patients received cisplatin plus 5FU (PF). The endpoints were overall survival (OS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS).ResultsThe median follow up time was 43months, with a range of 4–222months. The 3-year rates of OS, LFFS, and DMFS were 62.1%, 71.3%, and 82.4%, respectively. The 3-year OS for P and PF were 71.3% and 57.5% (p=0.27).A multivariate analysis revealed that various chemotherapy regimens displayed no statistical difference for OS (Hazard Ratio [HR]=1.81; 95% Confidence Interval [CI]=0.963–3.408; p=0.065), LFFS (HR=0.98; 95% CI=0.458–2.127; p=0.973), and DMFS (HR=1.25; 95% CI=0.463–3.398; p=0.656).Grade 3 and 4 mucositis for P and PF group were 61.5% and 64.9%. A greater than grade 3 dermatitis for P and PF group were 7.7% and 14.9%.ConclusionPostoperative chemoradiotherapy with cisplatin alone appeared to have higher 3-year OS and lower severe mucositis and dermatitis than cisplatin plus 5FU.



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Establishment and characterization of an oral tongue squamous cell carcinoma cell line from a never-smoking patient

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Steven J. Wang, Saurabh Asthana, Annemieke van Zante, Chase M. Heaton, Janyaporn Phuchareon, Leighton Stein, Saito Higuchi, Tomoya Kishimoto, Charles Y. Chiu, Adam B. Olshen, Frank McCormick, Osamu Tetsu
ObjectiveThe rising incidence of oral tongue squamous cell carcinoma (OTSCC) in patients who have never smoked and the paucity of knowledge of its biological behavior prompted us to develop a new cell line originating from a never-smoker.Materials and methodsFresh tumor tissue of keratinizing OTSCC was collected from a 44-year-old woman who had never smoked. Serum-free media with a low calcium concentration were used in cell culture, and a multifaceted approach was taken to verify and characterize the cell line, designated UCSF-OT-1109.ResultsUCSF-OT-1109 was authenticated by STR DNA fingerprint analysis, presence of an epithelial marker EpCAM, absence of human papilloma virus (HPV) DNA, and SCC-specific microscopic appearance. Sphere-forming assays supported its tumorigenic potential. Spectral karyotype (SKY) analysis revealed numerical and structural chromosomal abnormalities. Whole-exome sequencing (WES) identified 46 non-synonymous and 13 synonymous somatic single-nucleotide polymorphisms (SNPs) and one frameshift deletion in the coding regions. Specifically, mutations of CDKN2A, TP53, SPTBN5, NOTCH2, and FAM136A were found in the databases. Copy number aberration (CNA) analysis revealed that the cell line loses chromosome 3p and 9p, but lacks amplification of 3q and 11q (as does HPV-negative, smoking-unrelated OTSCC). It also exhibits four distinctive focal amplifications in chromosome 19p, containing 131 genes without SNPs. Particularly, 52 genes showed >3- to 4-fold amplification and could be potential oncogenic drivers.ConclusionWe have successfully established a novel OTSCC cell line from a never-smoking patient. UCSF-OT-1109 is potentially a robust experimental model of OTSCC in never-smokers.



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