Mycotoxins as human carcinogens—the IARC Monographs classification

Abstract

Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)—through its IARC Monographs programme—has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B₁, B₂, G₁, G₂ and M₁), fumonisins (fumonisin B₁ and B₂) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis–should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans–could lead to the reclassification of OTA.

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Anatomical Study and Clinical Application of Facial Artery Perforator Flaps (FAPFs) in Intraoral Reconstruction: focusing on venous system

Publication date: Available online 26 November 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Wei-na Zhou, Lin-zhong Wan, Ping Zhang, Hua Yuan, Hong-bing Jiang, Yi-fei Du
ObjectiveFacial artery perforator flaps (FAPFs) were favored to repair intraoral and perinasal defects with convenient procedure and minimal donor-site morbidity. The purpose of this study was to investigate the anatomic features of FAPFs and presented its clinical application in intraoral reconstruction.Materials and MethodsFive cadaver specimens (10 sides) of head and neck regions and 90 clinical cases (90 sides) of neck dissection were analyzed to explore the facial venous drainage system of FAPFs. In addition, the anatomical features of facial artery and vein as well as marginal mandibular branch of facial nerve were investigated in cadaver specimens. Furthermore, the authors reviewed a series of 33 intraoral reconstruction cases using our designed FAPFs focusing on the flap survival and the types of facial venous drainage system.ResultsBased on cadaveric and clinical observation, facial vein drainage system could be divided into three types: type A drained into internal jugular vein (47%); type B drained into external jugular vein (37%); and type C drained into anterior jugular vein (16%). The mean distances between facial artery and vein at the region of FAPFs pedicle and tip were 2.79±0.51 mm and 10.24±0.70 mm, respectively. Most of the cases with our designed FAPFs obtained satisfactory aesthetic and functional outcomes, while three cases presented with venous congestion, all of which were encountered with type C facial vein drainage.ConclusionThis study improved the understanding of FAPFs anatomic features and clinical application in intraoral reconstruction. Our designed FAPFs could achieve a preferable intraoral defect reconstruction and type C facial vein drainage might be a risk factor to the flap survival.



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Clinical and Three-Dimensional Radiographic Evaluation of Autogenous Iliac Block Bone Grafting and Guided Bone Regeneration in Patients with Atrophic Maxilla

Publication date: Available online 26 November 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): B. Alper Gultekin, Erol Cansiz, M. Oguz Borahan
PurposeTo evaluate the rate of graft resorption in autogenous iliac bone grafting (IBG) and guided bone regeneration (GBR) in patients with atrophic maxilla.MethodsThe investigators performed a retrospective study involving patients requiring implant placement who underwent IBG or GBR. Volumetric changes of the graft sites were evaluated by imaging studies. The primary predictor and outcome variables were augmentation technique and rate of volumetric resorption, respectively. Secondary outcome variables included bone gain, success of grafting, insertion torque of implants, and requirement for vestibuloplasty.ResultsThe sample comprised 39 patients (GBR, 21; IBG, 18). One patient each in the IBG and GBR groups experienced temporary sensory disturbance at donor site and late exposure of non-resorbable membrane, respectively. The average values of percent volume reduction of the GBR and IBG groups were 12.26 ± 2.35 and 35.94 ± 7.94 after healing and 15.87 ± 1.99 and 41.62 ± 6.97 at last follow-up, respectively. The IBG group exhibited significantly higher reduction in bone volume than the GBR group at both time points (P = 0.001). The mean values of horizontal and vertical bone gain after healing in the IBG group were significantly higher compared to those in the GBR group (P = 0.006 and 0.001, respectively). The mean implant torque during implant placement in the GBR group was significantly higher compared to that in the IBG group (P = 0.024). The was no significant difference in the requirement for vestibuloplasty between the two groups (P > .05).ConclusionsAlthough both hard tissue augmentation approaches provide adequate volume of bone graft for implant insertion, IBG results in greater graft resorption at maxillary augmented sites than GBR. Clinicians should consider the differences in extent of graft resorption between the two methods while choosing the treatment approach.



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Evaluation of the oropharynx in class I and II skeletal patterns by CBCT

Abstract

Purpose

This study aimed to evaluate the dimensions of the oropharynx and its shape in the minimum cross-sectional area, in individuals with Class I and Class II skeletal patterns, using three-dimensional CBCT images.

Methods

Forty-two cone-beam computed tomography images of grown individuals were evaluated. The images were divided according to the patient's skeletal patterns. The dimensions of the oropharyngeal airway space were determined using the Dolphin Imaging software.

Results

The volume and the minimum cross-sectional area were greater in patients with a Class I skeletal pattern, with a median difference of 5379 mm³ and 86.8 mm², respectively. The anteroposterior and lateral diameters in the minimum cross-sectional area were also higher in Class I individuals (2.3 and 6.0 mm, respectively), but the ratio between them was not different.

Conclusions

The volume and the minimum cross-sectional area of the oropharynx, as well as the anteroposterior and lateral diameters, are lower in individuals with a class II skeletal pattern than in individuals with a class I skeletal pattern. There was no difference in the shape of the oropharynx in healthy individuals with different skeletal patterns.

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The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Abstract

Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.

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Dendritic cells in central nervous system autoimmunity

Abstract

Dendritic cells (DCs) operate at the intersection of the innate and adaptive immune systems. DCs can promote or inhibit adaptive immune responses against neuroantigens. While DC intrinsic properties, i.e., their maturation state or the subset they belong to, are important determinants of the outcome of an autoimmune reaction, tissue-specific cues might also be relevant for the function of DCs. Thus, a better understanding of the performance of distinct DC subsets in specific anatomical niches, not only in lymphoid tissue but also in non-lymphoid tissues such as the meninges, the choroid plexus, and the inflamed CNS parenchyma, will be instrumental for the design of immune intervention strategies to chronic inflammatory diseases that do not put at risk basic surveillance functions of the immune system in the CNS. Here, we will review modern concepts of DC biology in steady state and during autoimmune neuroinflammation.

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Repair of complex pharyngocutaneous fistula using a staged temporoparietal fascial flap

Publication date: Available online 25 November 2016
Source:American Journal of Otolaryngology
Author(s): Nicholas B. Abt, Priya Srikanth, Sidharth V. Puram, Daniel G. Deschler
IntroductionPCF is the most common major complication after salvage total laryngectomy (TL), especially for previously irradiated patients with laryngeal or hypopharyngeal cancer.Methods/resultsA 65-year-old woman presented with recurrent bilateral supraglottic SCC requiring salvage TL 5.5years after initial T1N0M0 epiglottic SCC resection. Her post-operative course was complicated by PCF development one month post-operatively and surgical fistula closure was delayed for adjuvant chemoradiotherapy. The fistula persisted despite local wound therapy, several primary closures, pectoralis flap reconstruction with multiple revisions, and extensive hyperbaric oxygen treatments. Given her prior history, she underwent a staged right temporoparietal fascial flap reconstruction for persistent complex fistula, with second-stage flap takedown and complete inset of the TPFF skin island into the PCF.ConclusionThis case demonstrates the utility of staged TPFF in complex PCF repair, with minimal morbidity, especially in a patient with prior irradiation and flap use that complicates tissue availability.



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Prospective, multicenter evaluation of balloon sinus dilation for treatment of pediatric chronic rhinosinusitis

Background

Although balloon sinus dilation is a treatment option for adults with chronic rhinosinusitis (CRS), there have been few studies performed in pediatric patients.

Methods

This study was designed as a prospective, multicenter, single-arm investigation. Children (2 to 21 years old) with CRS who had failed medical management were treated with balloon sinus dilation and followed to 6 months postprocedure.

Results

Fifty children were treated at 4 centers; 33 participants were 2 to 12 years old (mean ± standard deviation age: 6.6 ± 2.2 years) and 17 participants were >12 to 21 years (mean age: 15.7 ± 2.5 years). A total of 157 sinus dilations were attempted (98 maxillary, 30 frontal, and 29 sphenoid sinuses) and all were successful with no complications. Significant improvement in the Sinus and Nasal Quality of Life Survey (SN-5) was seen for all children between baseline and 6 months (4.6 ± 1.2 vs 1.7 ± 0.8; p < 0.0001) and 92% improved by a minimal clinically important difference (MCID) of 1.0 or more. Those children aged 2 to 12 years with standalone balloon dilation also showed significant SN-5 improvements between baseline and follow-up (4.5 ± 1.0 vs 1.9 ± 0.8; p < 0.0001). Multivariate regression analysis showed no differences or associations of SN-5 improvement at 6 months with the presence of allergy, asthma, or concomitant procedures. For adolescents, overall 22-item Sino-Nasal Outcome Test (SNOT-22) mean scores were also significantly improved at 6 months (42.2 ± 19.2 vs 10.4 ± 9.7; p < 0.0001).

Conclusion

Balloon sinus dilation is safe and appears effective for children with CRS aged 2 years and older.

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Olfaction in patients with allergic rhinitis: an indicator of successful MP-AzeFlu therapy

Background

The purpose of this study was to investigate the effect of MP-AzeFlu on olfaction and the interaction between severity of allergic rhinitis and olfactory improvement after therapy.

Methods

A prospective, multicenter, observational study was performed on 47 patients with persistent allergic rhinitis. Duration and severity of allergic rhinitis was diagnosed and classified using the modified Allergic Rhinitis and its Impact on Asthma (ARIA) criteria and the proof of allergen sensitization from positive skin-prick tests, specific immonoglobulin E (IgE) in serum, and nasal provocation response. Patients were treated with MP-AzeFlu (1 spray/nostril twice daily) over 3 months. Olfactory function was assessed at baseline and at 1 and 3 months of therapy using the "Sniffin' Sticks" test. In addition, a nasal symptom score was recorded on a visual analog scale (VAS) at each given time-point.

Results

MP-AzeFlu was found to be associated with a significant improvement in TDI score, from 23.7 at baseline to 34.2 at 1 month (p < 0.001) and 37.1 at 3 months (p < 0.001) of treatment. Furthermore, a highly significant improvement of symptoms over time (p < 0.001; VAS at baseline: 84.3; 1 month: 32.4; 3 months: 26.2) could be demonstrated. Most importantly, there was a highly significant interaction between the severity of allergic rhinitis and olfactory function (p < 0.001) and VAS (p < 0.001).

Conclusion

MP-AzeFlu is associated with olfactory improvement in persistent allergic rhinitis patients. Further, the modified ARIA severity classification is an indicator of patients' olfactory function. Moreover, assessment of olfaction seems to be a reliable indicator of the clinical success of antiallergic/antiinflammatory therapy.

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Correlation between the number of allergen sensitizations and immunoglobulin E: monosensitization vs polysensitization

Background

The purpose of this study was to determine if total serum immunoglobulin E (IgE) could predict monosensitization compared to polysensitization in patients with allergic rhinitis (AR).

Methods

This was a retrospective study of a cohort of 1073 patients who underwent allergy testing. Differences in total IgE level between unsensitized, monosensitized, and polysensitized subjects were calculated. Pearson correlation coefficient was calculated to determine whether there was a relationship between total IgE level and the number of positive allergen sensitizations. In addition, allergen sensitization class was calculated for each allergen sensitization and totaled for each patient. Pearson correlation coefficient was calculated to determine the relationship between total IgE level and weighted allergen sensitization by class.

Results

There were 159 patients who were monosensitized compared to 492 patients who were polysensitized. Of the monosensitized patients, almost 50% (74) were sensitized to one or both dust mites. Total IgE was higher in polysensitized patients compared to monosensitized compared to controls (p < 0.001). Pearson correlation coefficient between total IgE and number of positive allergen sensitizations was 0.465 (p ≤ 0.001). Pearson correlation coefficient between total IgE and allergen class–weighted sensitizations was 0.529 (p ≤ 0.001).

Conclusion

IgE level can be used to predict monosensitization vs polysensitization. There is a moderate correlation between total IgE sensitization and the number of positive allergen sensitizations, as well as allergen class–weighted sensitizations.

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Histamine H4 receptor gene polymorphisms: a potential predictor of oral H1 antihistamine efficacy for allergic rhinitis

Background

Our study aimed to investigate the associations between Histamine H4 receptor (HRH4) gene polymorphisms (rs77485247, rs74604924, and rs77041280) and oral H1 antihistamine efficacy for the treatment of allergic rhinitis (AR) patients.

Methods

A total of 142 AR patients were selected as a case group and 160 healthy individuals were recruited as a control group. Single nucleotide polymorphisms (SNPs) in the HRH4 gene were detected using direct sequencing. Serum immunoglobulin E (IgE), specific IgE, and eosinophil cationic protein (ECP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Clinical efficacy was evaluated by the visual analogue scale (VAS). The occurrence of adverse reaction was recorded.

Results

There were significant differences in the distribution frequencies of mutant genotype (TA + AA) and A allele of rs77485247, mutant genotype (AT + TT) and T allele of rs74604924, and mutant genotype (AT + TT) and T allele of rs77041280 between the case and control groups. AR patients with mutant genotype (TA + AA) of rs77485247 and AR patients with mutant genotype (AT + TT) of rs77041280 had higher specific IgE, ECP levels, and VAS scores after treatment and lower incidence of adverse reactions and total effective rate than those with TT genotype and those with AA genotype, respectively. However, for rs74604924, there were no differences was found between AR patients with mutant genotype (AT + TT) and those with AA genotype.

Conclusion

Our findings provide evidence that HRH4 rs77485247 and rs77041280 polymorphisms may be associated with the risk of AR and the efficacy of H1 antihistamines for the treatment of AR patients.

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Myrtol standardized affects mucociliary clearance

Background

Myrtol standardized (Gelomyrtol forte) has been shown to be effective in controlling nasal symptoms of rhinosinusitis by promoting mucociliary clearance. Our aim was to evaluate the short- and long-term effects of myrtol on ciliated columnar cells and goblet cells in an in-vitro setting.

Methods

Nasal epithelial cells were harvested (42 days) from an air-liquid interface (ALI) culture of human nasal epithelial stem/progenitor cells (hNESPCs), which was derived from biopsies of nasal inferior turbinate mucosa. Myrtol 0.1% was applied to the ALI culture system at 2 different time-points (day 0 and day 35) on progenitor and differentiated cells. Ciliary beat frequency (CBF), supernatant fluid, and ciliated and goblet cell markers were evaluated after short- (7 days) and long-term (42 days) treatment.

Results

In the long-term treatment with myrtol, there was an increase in cilia area (type IV β-tubulin⁺, 1.53-fold, p = 0.031) and ciliogenesis-related markers (Foxj1 and CP110) with no change in CBF, as compared with control. In addition, the short-term myrtol treatment group exhibited greater mucin secretion compared with control.

Conclusion

This study demonstrates, through cellular and molecular mechanisms, that myrtol standardized enhances the mucus production from goblet cells in the short term, and promotes ciliated cell differentiation in the long term.

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Should surgeons routinely inform patients about risks of taste dysfunction after tongue base surgery for sleep apnea?

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Microarray analysis of the genes associated with osteitis in chronic rhinosinusitis

Objectives/Hypothesis

Although numerous studies have examined epithelial remodeling in chronic rhinosinusitis (CRS), bone remodeling (osteitis) has only recently gained attention as a potential significant contributor to the pathophysiology of recalcitrant CRS. The purpose of this study was to compare gene expression profiles between osteitic bone and the adjacent diseased mucosa in patients with CRS to determine which genes affect mucosal and bony remodeling.

Study Design

Prospective experimental analysis.

Methods

Samples were obtained from sites of osteitic bone and overlying mucosa in CRS patients demonstrating osteitis on computed tomography and compared to healthy controls. The entire transcripted gene expression profile was determined by microarray following RNA isolation and compared between tissue samples. The expression differences were verified by reverse transcriptase-polymerase chain reaction and immunohistochemical staining.

Results

Growth differentiation factor 5 and exostosin glycosyltransferase 1 were significantly upregulated and positively correlated with mucosal eosinophilic inflammation in osteitic bone. Fibroblast growth factor was significantly increased in osteitic bone. Additionally, colony stimulating factor was positively correlated with the degree of osteitis.

Conclusions

These findings will add a new perspective to our current understanding of the recalcitrant CRS.

Level of Evidence

NA Laryngoscope, 2016

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Carotid artery and lower cranial nerve exposure with increasing surgical complexity to the parapharyngeal space

Objectives/Hypothesis

To investigate the extent of carotid artery exposure attained, including the identification of the external carotid branches and lower cranial nerves in five sequential external approaches to the parapharyngeal space, and to provide an anatomical algorithm.

Study Design

Anatomical study.

Methods

Six latex-injected adult cadaver heads were dissected in five consecutive approaches: transcervical approach with submandibular gland removal, posterior extension of the transcervical approach, transcervical approach with parotidectomy, parotidectomy with lateral mandibulotomy, and parotidectomy with mandibulectomy. The degree of carotid artery exposure attained, external carotid branches, and lower cranial nerves visualized was documented.

Results

The transcervical approach exposed 1.5 cm (Standard Deviation (SD) 0.5) of internal carotid artery (ICA) and 1.25 cm (SD 0.25) of external carotid artery (ECA). The superior thyroid and facial arteries and cranial nerve XII and XI were identified. The posterior extension exposed 2.9 cm (SD 0.7) of ICA and 2.7 cm (SD 1.0) of ECA. Occipital and ascending pharyngeal arteries were visualized. The transparotid approach exposed 4.0 cm (SD 1.1) of ICA and 3.98 cm (SD 1.8) of ECA. Lateral mandibulotomy exposed the internal maxillary artery, cranial nerve X, the sympathetic trunk, and 4.6 cm (SD 2.4) of ICA. Mandibulectomy allowed for complete ECA exposure, cranial nerve IX, lingual nerve, and 6.9 cm (SD 1.3) of ICA.

Conclusion

Approaches for the parapharyngeal space must be based on anatomic and biological patient factors. This study provides a guide for the skull base surgeon for an extended approach based on the desired anatomic exposure.

Level of Evidence

N/A. Laryngoscope, 2016

http://ift.tt/2g3BY75

Aberrant cytoplasmic expression of MHCII confers worse progression free survival in diffuse large B-cell lymphoma

http://ift.tt/2gsfnxN

Complement in the fundamental processes of the cell

Publication date: Available online 25 November 2016
Source:Molecular Immunology
Author(s): Owen A. Hawksworth, Liam G. Coulthard, Trent M. Woodruff
Once regarded solely as an activator of innate immunity, it is now clear that the complement system acts in an assortment of cells and tissues, with immunity only one facet of a diverse array of functions under the influence of the complement proteins. Throughout development, complement activity has now been demonstrated from early sperm-egg interactions in fertilisation, to regulation of epiboly and organogenesis, and later in refinement of cerebral synapses. Complement has also been shown to regulate homeostasis of adult tissues, controlling cell processes such as migration, survival, repair, and regeneration. Given the continuing emergence of such novel actions of complement, the existing research likely represents only a fraction of the myriad of functions of this complex family of proteins. This review is focussed on outlining the current knowledge of complement family members in the regulation of cell processes in non-immune systems. It is hoped this will spur research directed towards revealing more about the role of complement in these fundamental cell processes.



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Venous malformations of the head and neck: current concepts in management

Publication date: Available online 25 November 2016
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): C. Fowell, C. Verea Linares, R. Jones, H. Nishikawa, A. Monaghan
Low-flow venous malformations are congenital lesions and they are the third most common vascular anomaly in the head and neck. In this paper, the third in a series of three educational reviews, we discuss current trends in their management, and include a summary of common sclerosant agents used in their control.



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Intraoperative, surgeon-view, high-definition video broadcasting in intraoral surgery

Publication date: Available online 25 November 2016
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R.-M. Baek, Y. Myung




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Patterns of dysphagia and acute toxicities in patients with head and neck cancer undergoing helical IMRT±concurrent chemotherapy

Publication date: January 2017
Source:Oral Oncology, Volume 64
Author(s): Laura B. Moroney, Jennifer Helios, Elizabeth C. Ward, Jane Crombie, Leesa F. Wockner, Clare L. Burns, Ann-Louise Spurgin, Claire Blake, Lizbeth Kenny, Brett G.M. Hughes
BackgroundThere is limited prospective data reporting the extent of treatment related toxicities associated with helical Intensity Modulated Radiotherapy (H-IMRT) for head and neck cancer (HNC). The study aim was to investigate severity, peak incidence and recovery patterns of dysphagia and related toxicities in patients undergoing H-IMRT±chemotherapy to examine when patients are experiencing symptoms requiring supportive clinical care.MethodsProspective study of 212 patients undergoing H-IMRT. Dysphagia and associated acute toxicities were monitored weekly during treatment and at weeks 2, 4 and 12 post treatment using the CTCAE v4, Functional Oral Intake Score and National Dysphagia Diet Descriptors.Results75% experienced Grade 2–3 dysphagia. Over 70% had grade 2–3 dysguesia, xerostomia, and thick saliva, and >50% experienced grade 2–3 pharyngeal mucositis, oral mucositis, and nausea. 13% patients declined to NBM requiring complete enteral nutrition, 25% required enteral nutrition but maintained some form of oral intake. Symptoms peaked in final week of treatment, consistently improving thereafter, with the majority better than baseline by 12 weeks post-treatment. Concurrent chemotherapy at least doubles the odds of experiencing most symptoms excepting xerostomia, taste and fluid level.ConclusionDespite advancements in radiation techniques, results confirm a high proportion of HNC patients experience dysphagia and related toxicities requiring supportive care during H-IMRT. Patients receiving H-IMRT alone experience a lower incidence of symptoms compared with those receiving concurrent chemotherapy. The data confirms the ongoing need for active on treatment monitoring with implications for the timing and intensity of patient support services.



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Oral extramedullary plasmacytoma in a HIV positive patient

Publication date: Available online 25 November 2016
Source:Oral Oncology
Author(s): Premalatha Shetty, Flora D. Lobo, R. Arvind, Sameep S. Shetty




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Tenosynovial giant cell tumors of the temporomandibular joint and lateral skull base: Review of 11 cases

Objectives

To elucidate the clinical behavior, treatment, and outcomes of tenosynovial giant cell tumors (TGCT) involving the temporomandibular joint (TMJ) and adjacent temporal bone.

Study Design

Retrospective case series with histopathologic review.

Methods

A retrospective chart review was performed identifying and collecting data from all cases of TGCT involving the TMJ and adjacent temporal bone that were treated at the authors' center between January 1960 and December 2015.

Results

Eleven histopathologically confirmed cases met inclusion criteria. The median age at diagnosis was 49 years, eight patients were men, and the median follow-up was 116 months. Computed tomographic (CT) imaging revealed a lytic expansile mass centered on the TMJ. Magnetic resonance imaging (MRI) most commonly exhibited hypointense signal on precontrast T1- and T2-weighted sequences and variable postcontrast enhancement. The median delay in diagnosis was 24 months, and the most common presenting symptoms were hearing loss and pain. All patients underwent surgical resection, eight receiving gross total removal, one receiving near total removal, and two patients from early in the series receiving subtotal resection with neoadjuvant or adjuvant radiation. Histopathological review of surgical specimens revealed chondroid metaplasia in seven tumors. Eight of nine cases receiving gross total or near total resection have no evidence of recurrence to date.

Conclusions

TGCT of the TMJ and temporal bone are rare and locally aggressive tumors that commonly present with nonspecific symptoms. A careful review of CT and MRI followed by early biopsy is critical in establishing an accurate diagnosis and facilitating appropriate treatment. TGCT of the TMJ more commonly contain chondroid metaplasia when compared to TGCT at other anatomic locations. Gross total resection is achievable in most cases and offers long-term cure. Radiation may be considered for recurrent disease or adjuvant therapy following subtotal resection.

Level of Evidence

4. Laryngoscope, 2016

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Outcomes following laryngectomy refusal after insufficient response to induction chemotherapy

Objective

To review patients who refused a total laryngectomy and were treated with radiotherapy (RT) after insufficient response to induction chemotherapy in a larynx preservation protocol for advanced-stage cancer of the larynx and to compare their outcomes with good responders.

Study Design

Retrospective cohort study.

Methods

Eighty-six patients treated with induction chemotherapy followed by RT were included in the analysis: 75 good responders and 11 insufficient responders who refused surgery. We compared overall survival (OS), disease-free survival (DFS), and laryngo-esophageal dysfunction-free survival (LEDFS) of the cohort populations in univariate and multivariate analyses.

Results

The median follow-up was 44 months. The 2-year and 5-year survival rates were respectively 72.2% and 58.8% for OS, 62.8% and 49.4% for DFS, and 59.5% and 44.3% for LEDFS. No survival endpoint was significantly decreased among insufficient responders, contrary to what we expected. When we focused on patients with an initially fixed larynx, the recovery of larynx mobility after induction chemotherapy was not associated with OS (P = 0.6055), DFS (P = 0.459), or LEDFS (P = 0.7403).

Conclusion

To the best of our knowledge, our study is the first patient treatment evaluation focused on subjects who refused a total laryngectomy after insufficient response to induction chemotherapy in a larynx preservation protocol for advanced-stage cancer of the larynx. Surprisingly, these patients treated with RT in our cancer center did not experience decreased functional and oncologic outcomes compared to good responders. Further studies will explore the relevance of response criteria and their evaluation methods.

Level of Evidence

4. Laryngoscope, 2016

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Antibiotics in eosinophilic chronic rhinosinusitis: Rethinking maximal antimicrobial medical therapy

Objectives/Hypothesis

Eosinophilic chronic rhinosinusitis (eCRS) has recently been recognized as a CRS subtype characterized by inflammation rather than chronic infection. Consequently, the role of antibiotics as a component of maximal medical therapy for eCRS has been called into question. The purpose of this study was to investigate whether the use of antibiotics, which lack any secondary anti-inflammatory properties, are useful in the treatment of eCRS.

Study Design

Prospective individual cohort study.

Methods

Institutional review board–approved, prospective study of 39 patients presenting with chronic rhinosinusitis (CRS). In all patients, Lund-Kennedy endoscopy scores, Lund-Mackay computed tomography scores, and Sino-Nasal Outcome Test-22(SNOT-22) scores were obtained before and after treatment with amoxicillin–clavulanic acid twice a day (625 mg) for 4 weeks. Patients were subsequently stratified into eCRS and non-eCRS groups based on having over 10 eosinophils per high-power field by histopathological examination. The efficacy of antibiotic therapy was compared between groups using the nonparametric Mann–Whitney U test.

Results

Within the non-eCRS group (n = 14), there was a significant improvement in both the Lund-Mackay score (P = .002) and SNOT-22 score (P < .001) but not the endoscopy score. Among the eCRS patients (n = 25), the Lund-Mackay score was similarly improved (P = .007); however, there was no significant improvement in the endoscopy or SNOT-22 scores.

Conclusions

The use of antibiotics without independent anti-inflammatory properties have limited efficacy in patients with eCRS. The concept of maximal medical therapy using antibiotics must continue to evolve in the setting of new evidence for inflammatory subtypes of CRS.

Level of Evidence

2b. Laryngoscope, 2016

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CD44 induces FOXP3 expression and is related with favorable outcome in breast carcinoma

Abstract

We studied the relationship between CD44 and Forkhead box P3 (FOXP3) gene expression in cell lines and breast carcinomas and their association with clinicopathological variables and patient outcome. We assessed messenger RNA (mRNA) expression of CD44 and FOXP3 by quantitative real-time PCR and determined the number of FOXP3+ Tregs by immunohistochemistry in 264 breast cancer specimens. CD44 was stimulated with hyaluronan treatment, and the accompanying changes in FOXP3 mRNA expression in breast cancer cell lines representing breast cancer subtype were assessed. We found that lower CD44 expression correlated with the presence of necrosis, lymph-vascular invasion, grade 3 tumors, and aggressive phenotype (HER2 and basal-like). FOXP3 mRNA correlated positively with CD44 mRNA expression and Treg content. Moreover, stimulation of CD44 expression by hyaluronan in cell lines increased FOXP3 expression, which supports that their regulation is associated. Survival analysis revealed that low CD44 expression is associated with higher frequency of recurrence. Our findings indicate that CD44 has a regulatory role in FOXP3 expression and is associated with good prognostic factors in breast cancer.

http://ift.tt/2fypvUR

Dermatological content of UK undergraduate curricula: where are we now?

Abstract

Given its impact, prevalence and especially its prominence in primary care ¹, the importance of all medical graduates developing knowledge and awareness of skin disease ought to go without saying. Yet a previous audit of undergraduate teaching against the recommendations of the British Association of Dermatologists (BAD) identified important omissions in the courses of some medical schools ². We recently undertook a survey of all medical schools in the UK and Ireland to investigate whether this had changed. The benchmark for course content derived from the BAD recommendations for undergraduates.

This article is protected by copyright. All rights reserved.

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