Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

Int J Dev Biol. 2017;61(8-9):557-563

Authors: Shin JO, Ankamreddy H, Jakka NM, Lee S, Kim UK, Bok J

Abstract
The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.

PMID: 29139542 [PubMed - in process]

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Patient-reported benefits from patient organization magazines and Internet-based peer support in Ménière's disease.

Related Articles

Patient-reported benefits from patient organization magazines and Internet-based peer support in Ménière's disease.

Patient Prefer Adherence. 2017;11:1851-1857

Authors: Manchaiah V, Pyykkö I, Zou J, Levo H, Kentala E

Abstract
Objectives: To facilitate self-help, the Finnish Ménière's Federation (FMF) provides various kinds of support to persons with Ménière's disease (MD), which includes patient magazines (PM) and Internet-based peer support (iPS). The current study aimed to evaluate the benefits reported by MD patients in terms of PM and iPS.
Method: The study used a cross-sectional survey design with a mixture of structured and open-ended questions administered online. A sample of 185 patients from the FMF membership database provided complete data.
Results: Ninety-two percent of the respondents rated PM as useful, or very useful. The main benefits of PM included: information on the disease and complaints, information about elements of peer support program, patient's experience with useful positive case studies, relevant news on MD, and information of activity of the FMF. Of the 185 persons, 68 reported that they did not have a need for peer support as their disease was either in silent phase or did not cause any annoyance. The main reasons for nonuse were: mild disease, personal reasons, and problems in using. Regarding the benefits of iPS, 75% of recent and 64% of chronic MD patients said that they would benefit from such a program. The main benefits of iPS included: reliable information on the disease and its management, peer support useful for coping with the disease, information about managing MD symptoms, information about managing attitude, and information about therapy. Moreover, the study identified different groups of individuals, which included: nonusers of support from patient organizations, those who used the support but did not feel they benefited, and those who used and also benefited from such programs.
Conclusion: The current study results provide some information about the preferences of MD patients regarding different forms of support and could certainly prove helpful while developing wider support strategies.

PMID: 29138539 [PubMed]

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Behavioral outcomes of a novel, pelvic nerve damage rat model of fecal incontinence

Abstract

Background

Fecal incontinence (FI) has a multifactorial pathophysiology with a severe social impact. The most common cause for FI is pudendal nerve damage, which mostly occurs in women during or after labor. A better understanding of the pathophysiology is required to optimize treatment of FI. In this study, we evaluate the use of a novel pelvic nerve damage rat model of FI.

Methods

This new model simulates the forces on the pelvic floor during labor by prolonged transvaginal, retro-uterine intrapelvic balloon distention in female rats. Number of fecal pellets produced per day and defecation pattern was compared between the experimental and control group for 2 weeks. The cages of the rats were divided in food, nesting and latrine areas to evaluate changes in defecation pattern. The FI Index (FII) was calculated to assess the ratio of fecal pellets between the non-latrine areas and the total number of pellets. A higher score represents more random distribution of feces outside the latrine area.

Results

Total number of fecal pellets was higher in the experimental group as compared with the controls. In both groups most fecal pellets were deposited in the nesting area, which is closest to the food area. The experimental group deposited more fecal pellets in the latrine area and had a lower FII indicating less random distribution of feces outside the latrine area.

Conclusion

Transvaginal, retro-uterine intrapelvic balloon distention is a safe and feasible animal model simulating the human physiologic impact of labor by downwards pressure on the pelvic floor.

This study demonstrated that transvaginal, retro-uterine, intrapelvic balloon distention is a safe and feasible animal model for induction of fecal incontinence simulating the human physiologic impact of labor.

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Oropharyngeal dysphagia profiles in individuals with oculopharyngeal muscular dystrophy

Abstract

Background

Although dysphagia represents a hallmark manifestation of oculopharyngeal muscular dystrophy (OPMD), limited knowledge exists regarding the underlying nature of oropharyngeal swallowing impairments in this patient population. We aimed to delineate global pharyngeal dysphagia profiles in OPMD and identify the prevalence and physiologic associations of impairments in swallowing safety and efficiency.

Methods

Twenty-two individuals with OPMD completed a videofluoroscopic swallowing evaluation. Blinded raters completed validated scales of global dysphagia (dynamic imaging grade of swallowing toxicity, DIGEST), efficiency (normalized residue ratio scale, NRRS), and safety (penetration-aspiration scale, PAS). Degree of laryngeal vestibule closure and aspiration events were described. Descriptives and chi-squared analyses were conducted with alpha set at P < .05.

Key Results

One hundred and thirty-four swallowing trials were analyzed. DIGEST scores revealed that 96% (n = 21) of participants demonstrated pharyngeal dysphagia (score >1). Presence of a cricopharyngeal bar was noted in 10 individuals. The predominant swallowing categorization across patients was safe and inefficient (51%) followed by unsafe and inefficient (32%). 77.3% demonstrated vallecular residue (NRRSv>0.07) and 90.1% piriform sinus residue (NRRSp > .20). 33% (n = 54) of swallows were unsafe (PAS>3) with 45 episodes of penetration and 9 episodes of aspiration. Aspiration occurred during the swallow in 100% of identified occurrences. Incomplete epiglottic inversion was associated with airway compromise and postswallow residue (P < .05).

Conclusions & Inferences

These findings highlight the high prevalence of oropharyngeal swallowing impairments in both swallowing efficiency and safety. A high proportion of physiologic impairments in epiglottic inversion and laryngeal vestibule closure were noted that related to functional impairments in swallow safety and inefficiency.

Although dysphagia is common in individuals with oculopharyngeal muscular dystrophy (OPMD), few studies have studied swallowing efficiency profiles and contributing pathophysiology in this population. The aims of this paper were to (i) delineate swallowing profiles and (ii) determine pathophysiology of swallowing inefficiency in individuals with OPMD. Elucidating specific pathophysiology contributing to dysphagia provides rationale for dysphagia treatment including implementation of rehabilitative and compensatory strategies.

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Cover Image

The cover image, by H. Ohkubo et al., is based on the Original Article Efficacy of percutaneous endoscopic gastro-jejunostomy (PEG-J) decompression therapy for patients with chronic intestinal pseudo-obstruction (CIPO), DOI: 10.1111/nmo.13127.

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Issue Information

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Chronic intestinal pseudo-obstruction: Progress in management?

Abstract

Chronic intestinal pseudo-obstruction (CIPO) is a severe form of gastrointestinal dysmotility (often due to derangement of the innervation/smooth muscle/interstitial cells of Cajal) with recurrent episodes of intestinal subocclusion mimicking a mechanical obstruction. Because of its complexity and heterogeneity, CIPO is often misdiagnosed or remains unrecognized until advanced stages. Management is a critical aspect in CIPO patient care. So far, most prokinetic drugs have not proven efficacy in restoring intestinal propulsion, thus nutritional support, fluid/electrolyte replacement, and antibiotics are the mainstay of treatment. In this issue of the journal, Ohkubo et al showed promising data indicating that percutaneous endoscopic gastro-jejunostomy (PEG-J) can be proposed as a measure for intestinal decompression, thereby improving CIPO-associated abdominal symptoms, including pain. In addition to a concise update of clinical and diagnostic features, the present minireview tackles management options, with a major emphasis on PEG-J, for CIPO patients.

Abbreviated abstract: Chronic intestinal pseudo-obstruction (CIPO) is one of the most severe forms of gastrointestinal dysmotility with many debilitating and potentially life-threatening symptoms / manifestations. Since most drugs failed to restore gastrointestinal coordinated motility, nutritional support, fluid / electrolyte replacement and antibiotics are still mandatory as life-saving measures. Promising data indicate that percutaneous endoscopic gastro-jejunostomy (PEG-J) can be proposed as a measure for intestinal decompression in CIPO, thereby improving symptoms and preventing malnutrition.

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Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

Int J Dev Biol. 2017;61(8-9):557-563

Authors: Shin JO, Ankamreddy H, Jakka NM, Lee S, Kim UK, Bok J

Abstract
The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.

PMID: 29139542 [PubMed - in process]

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Patient-reported benefits from patient organization magazines and Internet-based peer support in Ménière's disease.

Related Articles

Patient-reported benefits from patient organization magazines and Internet-based peer support in Ménière's disease.

Patient Prefer Adherence. 2017;11:1851-1857

Authors: Manchaiah V, Pyykkö I, Zou J, Levo H, Kentala E

Abstract
Objectives: To facilitate self-help, the Finnish Ménière's Federation (FMF) provides various kinds of support to persons with Ménière's disease (MD), which includes patient magazines (PM) and Internet-based peer support (iPS). The current study aimed to evaluate the benefits reported by MD patients in terms of PM and iPS.
Method: The study used a cross-sectional survey design with a mixture of structured and open-ended questions administered online. A sample of 185 patients from the FMF membership database provided complete data.
Results: Ninety-two percent of the respondents rated PM as useful, or very useful. The main benefits of PM included: information on the disease and complaints, information about elements of peer support program, patient's experience with useful positive case studies, relevant news on MD, and information of activity of the FMF. Of the 185 persons, 68 reported that they did not have a need for peer support as their disease was either in silent phase or did not cause any annoyance. The main reasons for nonuse were: mild disease, personal reasons, and problems in using. Regarding the benefits of iPS, 75% of recent and 64% of chronic MD patients said that they would benefit from such a program. The main benefits of iPS included: reliable information on the disease and its management, peer support useful for coping with the disease, information about managing MD symptoms, information about managing attitude, and information about therapy. Moreover, the study identified different groups of individuals, which included: nonusers of support from patient organizations, those who used the support but did not feel they benefited, and those who used and also benefited from such programs.
Conclusion: The current study results provide some information about the preferences of MD patients regarding different forms of support and could certainly prove helpful while developing wider support strategies.

PMID: 29138539 [PubMed]

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Headache in Resource-Limited Settings

Abstract

Purpose of Review

This review summarizes the unmet need of headache burden and management in resource-limited settings. It provides a general overview of the nuances and peculiarities of headache disorders in resource-limited settings. The review delivers perspectives and explanations for the emerging burden of both primary and secondary headache disorders. Important discussion on demographic and epidemiologic transition pertinent to low-resource settings is included. A critical analysis of headache disorders is made within the context of growing burden non-communicable disorders in low-resource countries. Challenges are examined and prospective feasible solutions tailored to existing resources are provided to address headache disorders in resource-limited settings.

Recent Findings

Many low-resource countries are entering into the third epidemiological transition featuring increasing burden of non-communicable disorders of which headache disorders contribute a significant proportion. Exponential population growth involving youthful demographic and massive rural-urban migration is taking place in low-resource countries. Youthful demographic is the natural cohort for primary headache such as migraine. Socioeconomic mobility and lifestyle changes are leading to higher levels of physical inactivity and obesity, both of which are related to headache. Life expectancy is rising in some resource-restricted countries; this increases prevalence of secondary headache attributed to neurovascular causes. Many low-resource countries are still burdened with tropical infectious causes of secondary headache. Health care facilities are primarily designed to respond to infectious epidemic and not to chronic burden such as headache. Many low-resource-restricted settings are plagued by poor and corrupt governance, ill-equipped regimes with malfunctioning health policies, war, and poverty. Many low-resource settings do not have access to generic headache medications such as triptans. Headache training and expertise is low. Healthy lifestyle changes emphasizing on improving regular exercise can be inexpensive method to reducing primary headache burden and its comorbidities (e.g. obesity).

Summary

Addressing the increasing burden of headache disorders in resource-limited settings is important to avert accrued disability which in turn lowers productivity and socioeconomic performance in a young booming population.

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Head and neck rhabdomyosarcoma in children: a 20-year retrospective study at a tertiary referral center

Abstract

Objective

The purpose of this study was to assess rhabdomyosarcomas (RMS) of the head and neck in pediatric patients with regard to clinical presentation, treatment, and survival.

Methods

Data were retrospectively obtained from patient charts with regard to RMS of the head and neck diagnosed between 1996 and 2016 at a tertiary referral center. Clinical course, treatment modalities, and side effects were analyzed. Survival analysis was carried out using the Kaplan–Meier method.

Results

Twenty-eight patients (17 male, 11 female) with a mean age at diagnosis of 6.8 ± 5.0 years have been included. Fourteen patients (50%) presented with painless swelling in the head and neck region and nine patients (32.1%) presented with cranial nerve deficit at initial diagnosis. The location of the majority of rhabdomyosarcomas was orbital (N = 9; 32.1%), followed by parapharyngeal (n = 4; 14.2%) and sinonasal (n = 3; 10.7%). All patients (n = 28; 100%) received polychemotherapy, additional adjuvant radiation therapy was carried out in 24 patients (85.7%), and surgery was performed in 12 cases (42.9%). The 5-year overall survival was 91.3%, and median progression-free survival was 46 ± 67.4 months. Common side effects resulting from chemotherapy and radiation therapy included neutropenia, mucositis, nausea and vomiting, and radiodermatitis, long-term side effects included microsomia and facial mutilation.

Conclusion

Multimodality treatment of rhabdomyosarcomas of the head and neck in pediatric patients may lead to a 5-year overall survival of up to 91.3%.

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Considerations in performing and analyzing the responses of cortico-cortical evoked potentials in stereo-EEG

Summary

This review aims to highlight key considerations when performing cortico-cortical evoked potentials (CCEPs) using stereo–electroencephalography (SEEG) for network mapping and show its clinical applicability to presurgical evaluations. The parameters for performing stimulation and safety aspects have been investigated in electrocorticography (ECoG) and deep brain stimulation (DBS), but not as extensively in SEEG. A review of current literature was performed, with an attempt made to emphasize practical insights from all modalities of intracranial stimulation. This paper reviews physical stimulation parameters, highlights safety limits, and considers the influence of changing common stimulation parameters. These factors are put into the context of CCEPs in SEEG. Given the paucity of direct research in this area, studies utilizing low frequency stimulation, DBS, and ECoG are incorporated along with the fundamental principles of electrical engineering. In addition, postprocessing considerations are reviewed, including electrode localization, application of digital filters, baseline selection, application of connectivity metrics, and higher order network analysis. The aim is to guide CCEP stimulation as well as to provide an understanding of the underlying principles of this technique. At present, there are few articles detailing the design of low-frequency stimulation paradigms, especially in the setting of SEEG. Providing a review of the fundamentals and postprocessing considerations when performing CCEPs in SEEG will increase the accessibility of this technique.

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Using Intraoral Scanning Technology for Three-Dimensional Printing of Kennedy Class I Removable Partial Denture Metal Framework: A Clinical Report

Abstract

Removable partial dentures (RPDs) are used to restore missing teeth and are traditionally fabricated using the lost-wax casting technique. The casting process is arduous, time-consuming, and requires a skilled technician. The development of intraoral scanning and 3D printing technology has made rapid prototyping of the RPD more achievable. This article reports a completed case of direct fabrication of a maxillary RPD metal framework (Kennedy Class I) using intraoral scanning and 3D printing techniques. Acceptable fit and satisfactory clinical outcome were demonstrated. Intraoral scanning and 3D printing for fabrication of the RPD metal framework is a useful alternative to conventional impression and casting techniques, especially for patients suffering from nasal obstruction or intolerance.

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Intraoperative Techniques for the Plastic Surgeon to Improve Pain Control in Breast Surgery

Summary: In recent years, there has been a growing emphasis placed on reducing length of hospital stay and health costs associated with breast surgery. Adequate pain control is an essential component of enhanced recovery after surgery. Postoperative pain management strategies include use of narcotic analgesia, non-narcotic analgesia, and local anesthetics. However, these forms of pain control have relatively brief durations of action and multiple-associated side effects. Intraoperative regional blocks have been effectively utilized in other areas of surgery but have been understudied in breast surgery. The aim of this article was to review various intraoperative techniques for regional anesthesia and local pain control in breast surgery and to highlight areas of future technique development. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 15 November 2017. Received for publication July 19, 2017; accepted August 21,2017. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Andrew A. Gassman, MD, Division of Plastic Surgery, Department of Surgery, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, E-mail: Andrew.Gassman@tuhs.temple.edu Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Pre-treatment lymphopenia and indication of tumor-induced systemic immunosuppression in medulloblastoma

Abstract

The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA). Compared to the control group, we observed statistically significantly lower absolute lymphocyte counts (ALCs) and higher NLCRs in the medulloblastoma group. Our findings suggest the presence of tumor-induced systemic immune suppression in MB patients already present at the time of diagnosis, with potential implications for the development of immune therapies in this population.

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Dichloroacetate induced intracellular acidification in glioblastoma: in vivo detection using AACID-CEST MRI at 9.4 Tesla

Abstract

Intracellular pH (pH_i) plays an important role in the maintenance of normal cell function, and is maintained within a narrow range by the activity of transporters located at the plasma membrane. Modulation of tumor pH_i may influence proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on cellular pH. Amine and amide concentration-independent detection (AACID) is a recently developed CEST contrast method that is intracellular pH (pH_i) weighted. Dichloroacetate (DCA) can alter tumor pH_i by inhibiting the enzyme pyruvate dehydrogenase kinase causing reduced lactate (increasing pH_i), or by decreasing the expression of monocarboxylate transporters and vacuolar ATPase leading to reduced pH_i. Since the net in vivo effect of DCA on pH_i is difficult to predict, the purpose of this study was to quantify the magnitude of acute pH_i change in glioblastoma after a single DCA injection using AACID CEST MRI. Using a 9.4T MRI scanner, CEST spectra were acquired in six mice approximately 14 days after implanting 10⁵ U87 human glioblastoma multiforme (GBM) cells in the brain, before and after intravenous injection of DCA (dose: 200 mg/kg). Three additional mice received only phosphate buffered saline (PBS) injection and were studied as controls. Repeated measures t test was used to compare AACID changes in tumor and contralateral tissue regions of interest. One hour after DCA injection there was a significant increase in tumor AACID level by 0.04 ± 0.01 corresponding to a 0.16 decrease in pH_i, and no change in AACID in contralateral tissue. Inspection of AACID maps following PBS injection showed no differences. The use of DCA to induce a tumor specific pH change detectable by AACID CEST MRI is consistent with previous studies that have shown similar effects for lonidamine and topiramate. This study demonstrates that a single dose of DCA can be used as a pharmacological challenge to induced rapid tumor intracellular acidification.

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Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review

Abstract

Chronic uveitis is a common extra-articular manifestation of juvenile idiopathic arthritis. The classic clinical picture is one of chronic anterior uveitis, which usually remains asymptomatic until ocular complications arise. The risk of uveitis is increased in girls with an early onset of oligoarthritis and positive antinuclear antibodies. Even though the inflammation in patients with juvenile idiopathic arthritis is initially limited in the anterior part of the eye, chronic active inflammation may eventually cause significant damage to the posterior pole. Complications may include band keratopathy, cataract, secondary glaucoma, posterior synechiae, cystoid macular edema, and hypotony. The cooperation of ophthalmologists with rheumatologists may help define the best treatment plan. The ophthalmic therapeutic regimen includes topical corticosteroids and mydriatics, while in severe cases immunosuppressive and biological agents are introduced. Surgical management of complications might be needed.

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Prolonging Time to Flare in Pediatric Atopic Dermatitis: A Randomized, Investigator-Blinded, Controlled, Multicenter Clinical Study of a Ceramide-Containing Moisturizer

Abstract

Introduction

Delaying or preventing flares is important in atopic dermatitis (AD) management. The objective of the study was to evaluate whether using a ceramide-containing moisturizer in addition to a body wash during latent AD can delay flares.

Methods

This was a randomized, investigator-blinded, parallel-group, controlled study among Chinese children with a history of mild to moderate AD, within 1 week of successful treatment with a topical corticosteroid. Subjects were randomized to receive moisturizer twice daily and body wash once daily, or body wash alone once daily for 12 weeks. The primary efficacy endpoint was time to flare [necessitating medical therapy and/or Investigator Global Assessment (IGA) > 1 (at least mild AD)]. Other efficacy endpoints were AD characteristics and emollient effects. The patient-reported outcome comprised satisfaction at week 12. The safety endpoint was incidence of undesirable events.

Results

A total of 64 subjects aged 2–12 years were randomized. Median time to flare was delayed by nearly 2 months for moisturizer/body wash compared to body wash alone (89 vs. 27 days, respectively). A significantly earlier onset of action in terms of fewer flares favoring moisturizer was found at week 4 (31 vs. 59%, respectively, p = 0.022), and after 12 weeks, fewer flares occurred (50 vs. 72%). At week 12 for flare-free subjects, nearly half in both groups had clear IGA, and an emollient effect in terms of less dryness or burning was more marked for moisturizer/body wash. Both products led to high patient satisfaction and were well tolerated.

Conclusion

A regimen incorporating a moisturizer plus body wash delayed AD flares by nearly 2 months compared to body wash alone, and yielded high patient satisfaction.

Funding

Galderma R&D.

Trial Registration

ClinicalTrials.gov identifier, NCT02589392.

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Systematic Literature Review of the Impact of Endocrine Monotherapy and in Combination with Targeted Therapy on Quality of Life of Postmenopausal Women with HR+/HER2− Advanced Breast Cancer

Abstract

Introduction

A major treatment goal for advanced breast cancer (ABC) is to maintain or ideally improve patient quality of life (QoL). Given the changing disease landscape, this systematic literature review (SLR) aims to assess the impact of endocrine therapies (ET), including ET monotherapy (ET mono) and ET combined with targeted therapy (ET + TT), on QoL of women with HR+/HER2− ABC.

Methods

A SLR was conducted to identify randomized controlled trials (RCTs) meeting the following criteria: (1) included ET mono or ET + TT, (2) reported QoL outcomes, (3) focused on women with HR+/HER2− ABC, and (4) published after 2007 (when standardized HER2 testing became available). The databases searched included MEDLINE, EMBASE, Cochrane Library, and key conference proceedings from 2013 to 2016. QoL outcomes for ET mono, ET + TT, and comparisons between the two were summarized from the identified trials.

Results

A total of 11 studies (representing 6 RCTs) were identified. The study populations included first-line (5 studies) and ET-failure settings (6 studies). Across settings, global health status (GHS) maintained or deteriorated slightly on these treatments during the trial period. Time to deterioration (TTD) in QoL measured by GHS was analyzed in 6 studies and 4 RCTs. In the first-line setting, reported median TTD in GHS was similar between ET mono and ET + TT (7.2–13.8 months in ET mono; 11.1 months in ET + TT). In the ET-failure setting, ET + TT showed significantly longer TTD vs. ET mono in GHS (median 5.6–8.4 months in ET mono and 8.3–11.7 months in ET + TT) and some additional domains.

Conclusions

ET + TT users experienced similar QoL in the first-line and ET-failure setting relative to patients on ET mono. Moreover, ET + TT users experienced better QoL outcomes in some domains in the ET-failure setting relative to ET mono users.

Funding

Novartis.

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Pre-treatment lymphopenia and indication of tumor-induced systemic immunosuppression in medulloblastoma

Abstract

The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA). Compared to the control group, we observed statistically significantly lower absolute lymphocyte counts (ALCs) and higher NLCRs in the medulloblastoma group. Our findings suggest the presence of tumor-induced systemic immune suppression in MB patients already present at the time of diagnosis, with potential implications for the development of immune therapies in this population.

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Dichloroacetate induced intracellular acidification in glioblastoma: in vivo detection using AACID-CEST MRI at 9.4 Tesla

Abstract

Intracellular pH (pH_i) plays an important role in the maintenance of normal cell function, and is maintained within a narrow range by the activity of transporters located at the plasma membrane. Modulation of tumor pH_i may influence proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on cellular pH. Amine and amide concentration-independent detection (AACID) is a recently developed CEST contrast method that is intracellular pH (pH_i) weighted. Dichloroacetate (DCA) can alter tumor pH_i by inhibiting the enzyme pyruvate dehydrogenase kinase causing reduced lactate (increasing pH_i), or by decreasing the expression of monocarboxylate transporters and vacuolar ATPase leading to reduced pH_i. Since the net in vivo effect of DCA on pH_i is difficult to predict, the purpose of this study was to quantify the magnitude of acute pH_i change in glioblastoma after a single DCA injection using AACID CEST MRI. Using a 9.4T MRI scanner, CEST spectra were acquired in six mice approximately 14 days after implanting 10⁵ U87 human glioblastoma multiforme (GBM) cells in the brain, before and after intravenous injection of DCA (dose: 200 mg/kg). Three additional mice received only phosphate buffered saline (PBS) injection and were studied as controls. Repeated measures t test was used to compare AACID changes in tumor and contralateral tissue regions of interest. One hour after DCA injection there was a significant increase in tumor AACID level by 0.04 ± 0.01 corresponding to a 0.16 decrease in pH_i, and no change in AACID in contralateral tissue. Inspection of AACID maps following PBS injection showed no differences. The use of DCA to induce a tumor specific pH change detectable by AACID CEST MRI is consistent with previous studies that have shown similar effects for lonidamine and topiramate. This study demonstrates that a single dose of DCA can be used as a pharmacological challenge to induced rapid tumor intracellular acidification.

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Blood plasma biomarkers of citrinin and ochratoxin A exposure in young adults in Bangladesh

Abstract

Citrinin (CIT) and Ochratoxin A (OTA) are nephrotoxic mycotoxins which can co-occur in food commodities, resulting in internal exposure. Studies in many countries reported on the presence of OTA in human blood; however, such biomonitoring data for CIT is still scarce. This study was conducted to characterize both CIT and OTA biomarker levels in plasma of volunteers since food analysis data are insufficient to assess human exposure in Bangladesh. In total 104 blood samples were collected from university students in 2013 (sampling 1: n = 64, midsummer) and 2014 (sampling 2: n = 40, end winter) for analysis of CIT and OTA and their metabolites HO-CIT and OTα by LC-MS/MS and HPLC-FD techniques, respectively. CIT and HO-CIT were detected in 90% (max 2.70 ng/mL) and 85% (max 1.44 ng/mL) of all samples. Mean levels in sampling 2 (CIT 0.47 ng/mL; HO-CIT 0.40 ng/mL) were higher than in sampling 1 (0.25 ng/mL; 0.37 ng/mL) indicative of variable CIT exposure. OTA was present in all (max 6.63 ng/mL) and OTα in 98% (max 0.99 ng/mL) of the samples. In sampling 1, mean OTA (0.85 ng/mL) was higher than in sampling 2 (0.51 ng/mL); the reverse situation was found for OTα mean levels. The calculated dietary OTA intake among the students (mean 9.9; max 91.7 ng/kg bw/week) was lower than the tolerable weekly intake for this mycotoxin (120 ng/kg bw/week) set by EFSA. But frequent co-exposure to CIT should be considered, and the results of this study indicate the necessity to identify major sources of CIT and OTA intake in the Bangladeshi population.

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Morphometric properties of the latissimus dorsi muscle in human fetuses for flap surgery

Abstract

Purpose

Although latissimus dorsi (LD) flaps are extensively used in a wide range of interventions, fetus studies on this subject are quite limited. This study aims to obtain detailed information about the morphometric features of LD, thoracodorsal artery (TDA) and nerve (TDN).

Methods

The study was carried out on both sides of 50 formalin-fixed human fetuses (22 male/28 female) with a mean gestational age of 24.5 ± 4.7 (range 18–36) weeks, which were in the inventory of Anatomy Department of Mersin University Faculty of Medicine. Dimensions of LD, lengths and width of TDA and TDN were measured. Surface area of LD was calculated using digital image analysis software.

Results

All samples had LD muscle. Neither gender nor side-significant differences were observed in relation with the numerical data of LD, TDN and TDA. Linear function of surface area was calculated as "y = − 1767.532 + 114.582 × Age (weeks)". LD was attached directly to the posterior part of iliac crest in 59 of 100 sides meanwhile in the rest 41, it was attached by the thoracolumbar fascia. TDA gave a branch to serratus anterior in 96 cases and 2 branches in 4 cases. TDN passed superficial to TDA in 84 and deep to TDA in 16 samples. TDN had bifurcation in 93, trifurcation in 6 and tetrafurcation in 1 side.

Conclusion

Data obtained from this study can be useful for estimating the sizes of LD and related neurovascular structures, especially in neonate surgeries. Linear function of LD surface area can be helpful to design the flap dimensions in newborn surgeries. A throughout knowledge about the branching pattern of TDN and its location-wise relation with TDA should be kept in mind to prevent possible complications during harvesting LD flaps and TDN grafts.

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Fishtail deformity of the distal humerus: association with osteochondritis dissecans of the capitellum

Abstract

Background

Fishtail deformity is a rare deformity of the humerus exhibiting concavity of the lateral trochlea, resulting in ulnotrochlear joint derangement. We wanted to share our experience that osteochondritis dissecans of the capitellum is a common associated complication.

Objective

To summarize imaging of fishtail deformity in children centered on complications of the radiocapitellar joint.

Materials and methods

From the radiology information system, we identified all patients <18 years with the diagnosis of fishtail deformity. We included only patients with V-shaped deformity of the distal humerus due to concavity at the lateral trochlea (fishtail deformity). Each patient's initial injury, most recent radiograph and available MRI were evaluated for radiocapitellar joint derangement.

Results

Seven patients (4 males) with a mean age of 12.9 years (range: 9.7 to 14.4 years) were identified. Radiocapitellar joint abnormalities were identified in six patients including osteoarthritis (n=5), flattened and sclerotic capitellum (n=4), osteochondritis dissecans (2 associated with loose body, n=4) and radial head subluxation (n=2). In 4 patients, MRI detected changes of osteoarthritis (n=4), osteochondritis dissecans (n=2) and loose body (n=1) not identified on radiography. Two patients with osteochondritis dissecans underwent surgery and one patient has planned surgery.

Conclusion

Radiocapitellar joint abnormalities (particularly, capitellar osteochondritis dissecans) are common in patients with fishtail deformities. MRI should be performed in these patients since some abnormalities, possibly requiring surgery, are not detected on elbow radiographs.

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Identification of swallowing disorders in early and mid-stage Parkinson's disease using pattern recognition of pharyngeal high-resolution manometry data

Abstract

Background

Parkinson's disease (PD) can cause severe dysphagia, especially later in disease progression. Early identification of swallowing dysfunction may lead to earlier intervention. Pharyngeal high-resolution manometry (HRM) provides complementary information to videofluoroscopy, with advantages of being quantitative and objective. Artificial neural network (ANN) classification can examine non-linear relationships among multiple variables with relatively low bias. We evaluated if ANN techniques could differentiate between patients with PD and healthy controls.

Methods

Simultaneous videofluoroscopy and pharyngeal HRM were performed on 31 patients with early to mid-stage PD and 31 age- and sex-matched controls during thin-liquid swallows of 2 cc, 10 cc and comfortable sip volume. We performed multilayer-perceptron analyses on only videofluoroscopic data, only HRM data or a combination of the two. We also evaluated variability-based parameters, representing variability in manometric parameters across multiple swallows. We hypothesized that patients with PD and controls would be classified with at least 80% accuracy, and that combined videofluoroscopic and HRM data would classify participants better than either alone.

Key Results

Classification rates were highest with all parameters considered. Maximum classification rate was 82.3 ± 5.2%, recorded for 2 cc swallows. Inclusion of variability-based parameters improved classification rates. Classification rates using only manometric parameters were similar to those using all parameters, and rates were substantially lower for the comfortable sip volumes.

Conclusions & Inferences

Results from these classifications highlight the differences between swallowing function in patients with early and mid-stage PD and healthy controls. Early identification of swallowing dysfunction is key to developing preventative swallowing treatments for those with PD.

We evaluated if pattern recognition of pharyngeal high-resolution manometry with or without videofluoroscopy could be used to identify patients with early- and mid-stage Parkinson's disease. Classification accuracy exceeded 80%, and was similar when considering manometric parameters with and without videofluoroscopic parameters. Use of high-resolution manometry coupled with pattern recognition-based analysis may help clinicians identify early changes in swallowing function in patients with Parkinson's disease that could lead to earlier and potentially more effective treatment.

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Morphometric properties of the latissimus dorsi muscle in human fetuses for flap surgery

Abstract

Purpose

Although latissimus dorsi (LD) flaps are extensively used in a wide range of interventions, fetus studies on this subject are quite limited. This study aims to obtain detailed information about the morphometric features of LD, thoracodorsal artery (TDA) and nerve (TDN).

Methods

The study was carried out on both sides of 50 formalin-fixed human fetuses (22 male/28 female) with a mean gestational age of 24.5 ± 4.7 (range 18–36) weeks, which were in the inventory of Anatomy Department of Mersin University Faculty of Medicine. Dimensions of LD, lengths and width of TDA and TDN were measured. Surface area of LD was calculated using digital image analysis software.

Results

All samples had LD muscle. Neither gender nor side-significant differences were observed in relation with the numerical data of LD, TDN and TDA. Linear function of surface area was calculated as "y = − 1767.532 + 114.582 × Age (weeks)". LD was attached directly to the posterior part of iliac crest in 59 of 100 sides meanwhile in the rest 41, it was attached by the thoracolumbar fascia. TDA gave a branch to serratus anterior in 96 cases and 2 branches in 4 cases. TDN passed superficial to TDA in 84 and deep to TDA in 16 samples. TDN had bifurcation in 93, trifurcation in 6 and tetrafurcation in 1 side.

Conclusion

Data obtained from this study can be useful for estimating the sizes of LD and related neurovascular structures, especially in neonate surgeries. Linear function of LD surface area can be helpful to design the flap dimensions in newborn surgeries. A throughout knowledge about the branching pattern of TDN and its location-wise relation with TDA should be kept in mind to prevent possible complications during harvesting LD flaps and TDN grafts.

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A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers

Abstract

Purpose

FOLFIRINOX (FFN), nab-paclitaxel plus gemcitabine (GN), and gemcitabine are three systemic therapies that provide clinically meaningful benefit to patients with unresectable pancreatic cancer (UPC). There are no clinical trials that directly compare the efficacy of all three regimens. In this study, we aim to examine and compare the real-world effectiveness of these treatments.

Methods

Patients diagnosed with UPC who initiated palliative chemotherapy from August 2014 to January 2016 at any one of six cancer centers in British Columbia were identified from the provincial pharmacy. Clinical, pathological, treatment, and outcome characteristics were compared.

Results

Two hundred twenty-five patients were included: 55% men, 68% Eastern Cooperative Oncology Group 0/1, 58% metastatic disease. Patients who received FFN were younger (p < 0.001) and in better performance status (p < 0.001). Patients treated with FFN or GN experienced significantly longer median overall survival (OS) when compared to those treated with gemcitabine (14.1 vs 10.5 vs 4.2 months, respectively, p < 0.001). Progression-free survival (PFS) was also longer among patients on FFN or GN in comparison to gemcitabine (FFN, HR 0.44, 95% CI 0.24 to 0.814, p = 0.008; GN, HR 0.30, 95% CI 0.19 to 0.47, p < 0.001). A significantly higher proportion of patients require two or more dose modifications on FFN (40%) compared to GN (14%) or gemcitabine (9%) (p < 0.001).

Conclusions

Receipt of modified FFN and GN portends a better prognosis than gemcitabine alone. In the absence of a randomized comparison of all three regimens, our population-based study reveals that the introduction of modified FFN and GN confers real-world effectiveness for UPC patients.

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Anaplastic Lymphoma Kinase Testing: IHC vs. FISH vs. NGS

Opinion statement

Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4–7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin. The selection of patients based on their ALK status is vital on account of the high response rates with the ALK-targeted agents in this subset of patients. Standardization and validation of ALK rearrangement detection methods is essential for accurate and reproducible results. There are currently three detection methods widely available in clinical practice, including fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and polymerase chain reaction (PCR)-based next generation sequencing (NGS) technology. However, the choice of diagnostic methodology for ALK rearrangement detection in clinical practice remains a matter of debate. With accumulating data enumerating the advantages and disadvantages of each of the three methods, combining more than one testing method for ALK fusion detection may be beneficial for patients. In this review, we will discuss the current methods used in ALK rearrangement detection with emphasis on their key advantages and disadvantages.

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The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer

Opinion statement

Approximately 20% of patients with cancer of the stomach or gastro-oesophageal junction (GOJ) present with resectable disease. Long-term outcome after surgery alone in these patients is poor, and a combined treatment approach is the standard of care. The two approaches to managing patients with cancer of the GOJ are perioperative chemotherapy or preoperative chemoradiotherapy. Based upon the most recent evidence, patients treated with a perioperative approach and deemed suitable for a triplet regimen should be considered for pre- and post-operative FLOT (5-fluorouracil [5-FU], leucovorin, oxaliplatin and docetaxel) and those suitable for a doublet regimen should be considered for a fluoropyrimidine/platinum combination such as capecitabine and oxaliplatin. Alternatively, such patients may be considered for preoperative chemoradiotherapy according to the CROSS regimen. True gastric cancers may be treated with a perioperative approach or, as is commonly used in Asia, postoperative adjuvant chemotherapy.

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Update in the Therapy of Advanced Neuroendocrine Tumors

Opinion statement

Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of ~ 6.9/100,000. NETs arise throughout the body from cells of the diffuse endocrine system. More than half originate from endocrine cells of the gastrointestinal tract and the pancreas, thus being referred to as gastroenteropancreatic NETs (GEP-NETs). The only treatment that offers a cure is surgery; however, most patients are diagnosed with metastatic disease, and curative surgery is usually not an option. These patients can be offered long-term systemic treatment, for both symptomatic relief and tumor growth suppression. Evidence-based treatment options include somatostatin analogs, everolimus (a mTOR inhibitor), sunitinib (a tyrosine kinase inhibitor), and peptide receptor radionuclide therapy, alone or combined with cytoreductive procedures (surgery or liver-directed procedures). Other treatment options being investigated are immunotherapy and epigenetic assessment that may lead to more personalized interventions. We believe that each patient should be thoroughly evaluated and their case discussed by a multidisciplinary team that is up-to-date with all treatment modalities including ongoing clinical trials, before selecting the proper treatment option.

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Diagnosis and Treatment of Aplastic Anemia

Opinion statement

Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of early hematopoietic cells. Diagnosis of AA requires a comprehensive approach with prompt evaluation for inherited and secondary causes of bone marrow aplasia, while providing aggressive supportive care. The choice of frontline therapy is determined by a number of factors including AA severity, age of the patient, donor availability, and access to optimal therapies. For newly diagnosed severe aplastic anemia, bone marrow transplant should be pursued in all pediatric patients and in younger adult patients when a matched sibling donor is available. Frontline therapy in older adult patients and in all patients lacking a matched sibling donor involves immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporine A. Recent improvements in upfront therapy include encouraging results with closely matched unrelated donor transplants in younger patients and the emerging benefits of eltrombopag combined with initial IST, with randomized studies underway. In the refractory setting, several therapeutic options exist, with improving outcomes of matched unrelated donor and haploidentical bone marrow transplantation as well as the addition of eltrombopag to the non-transplant AA armamentarium. With the recent appreciation of frequent clonal hematopoiesis in AA patients and with the growing use of next-generation sequencing in the clinic, utmost caution should be exercised in interpreting the significance of somatic mutations in AA. Future longitudinal studies of large numbers of patients are needed to determine the prognostic significance of somatic mutations and to guide optimal surveillance and treatment approaches to prevent long-term clonal complications.

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The Multidisciplinary Approach to Localized Pancreatic Adenocarcinoma

Opinion statement

Pancreatic adenocarcinoma 2030 (PCa) is predicted to be the second leading cause of cancer death in USA by 2030. To date, attempts at early detection have been unsuccessful. Therapies for resectable PCa include surgery followed by adjuvant chemotherapy with or without radiotherapy. Unfortunately, most patients with PCa present with advanced disease and thus only 20% of patients are potentially resectable upon presentation. Improved surgical techniques along with adjuvant combination chemotherapy have improved outcomes for patients with resectable disease. The optimal treatment approach for borderline resectable and locally advanced unresectable PCa has not yet been defined. Despite significant advances in the palliative treatment of PCa, long-term survival of early stage disease continues to be sobering. The key to improving outcomes for this largely fatal disease is to identify multidisciplinary therapeutic interventions including surgical, medical, and radiation techniques tailored to the patient and their disease characteristics. The neoadjuvant approach provides an in vivo platform to test novel treatment options to help us understand tumor biology and surrounding microenvironment, which may ultimately help us achieve the goal of improvement in long-term survival. While the neoadjuvant approach remains popular as a way to optimally select patients that might benefit most from surgery, randomized trials utilizing adjuvant and neoadjuvant novel therapies hold the key to truly personalizing the ideal treatment strategy for localized PCa.

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Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: effects on allergic diseases

Abstract

Background

While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of sensitization and AD is less well defined.

Objective

We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk for developing allergic diseases within each pattern in a general cohort.

Methods

Children (n=2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly-sensitization to foods, and poly-sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group.

Results

Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%), and persistent sensitization (3.2%). Using healthy children as the baseline, children in the "atopic dermatitis" group had the next lowest risk for all allergic outcomes at 3 years; those in the "inhalant sensitization" group had the highest risk for allergic rhinitis; children in the "transient sensitization" group were at an increased risk for food allergy; while children in the "persistent sensitization" group had the highest risk for all allergic diseases.

Conclusion and Clinical Relevance

There is substantial heterogeneity among allergen-sensitized children. Researchers and clinicians need to be aware of the non-specificity associated with labelling children simply as "atopic" and "non-atopic" without considering the timing of their atopic history, type of sensitization, and AD status. Children with AD who were poly-sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.

This article is protected by copyright. All rights reserved.

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Asthma and Lung Function in Adulthood after a Viral Wheezing Episode in Early Childhood

Abstract

Background

Viral etiology of infection has a significant role in the long-term outcome of early-childhood wheezing.

Objective

This study examines asthma and lung function in adulthood after early-childhood wheezing induced by respiratory syncytial virus (RSV) and rhinovirus (RV).

Methods

A total of 100 children were hospitalized for a wheezing episode at less than 24 months of age from 1992 to 1993 in Kuopio University Hospital (Finland). Adenovirus, influenza A and B virus, parainfluenza (1-3) virus, and RSV were tested on admission using antigen detection and antibody assays, and RSV and RV were tested by polymerase chain reaction (PCR). In 2010, 49 cases and 60 population controls attended a follow-up study, which included spirometry with bronchodilation test and fractionally exhaled nitric oxide (FE_NO) measurements.

Results

Current asthma was present in 64% of the cases with RV-induced wheezing [OR 17.0 (95%CI 3.9-75.3) vs. controls], in 43% of the cases with RSV-induced wheezing episode [6.1 (1.5-24.9) vs. controls], and in 12% of the controls. The RV group showed significantly higher mean FE_NO values than the RSV group and controls. RV-positive cases had lower MEF50 before bronchodilation and higher MEF50, FEV1, and FEV1/FVC bronchodilation responses than controls. RSV-positive cases had lower FVC than controls before bronchodilation.

Conclusion

Cases with RV- and RSV-induced early-childhood wheezing had increased risk for asthma in adulthood, and RV-positive cases had significantly higher FE_NO values than RSV-positive cases and controls. Compared to controls RV-positive cases showed more bronchial reactivity, and RSV-positive cases showed lower FVC before bronchodilation in lung function testing.

Clinical relevance

Children with RV- or RSV-induced wheezing in early childhood have an increased risk for asthma and lung function abnormalities in adulthood.

This article is protected by copyright. All rights reserved.

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Accurate Prediction and Elucidation of Drug Resistance Based on the Robust and Reproducible Chemoresponse Communities

Abstract

Selecting the available treatment for each cancer patient from genomic context is a core goal of precision medicine, but innovative approaches with mechanism interpretation and improved performance are still highly needed. Through utilizing in vitro chemotherapy response data coupled with gene and miRNA expression profiles, we applied a network-based approach that identified markers not as individual molecules but as functional groups extracted from the integrated transcription factor and miRNA regulatory network. Based on the identified chemoresponse communities, the predictors of drug resistance achieved high accuracy in cross validation and were more robust and reproducible than conventional single-molecule markers. Meanwhile, as candidate communities not only enriched abundant cellular process but also covered a variety of drug enzymes, transporters and targets, these resulting chemoresponse communities furnished novel models to interpret multiple kinds of potential regulatory mechanism, such as dysregulation of cancer cell apoptosis or disturbance of drug metabolism. Moreover, compounds were linked based on the enrichment of their common chemoresponse communities to uncover undetected response patterns and possible multidrug resistance phenotype. Finally, an omnibus repository named ChemoCommunity (http://ift.tt/2AMUAPH/) was constructed, which furnished a user-friendly interface for a convenient retrieval of the detailed information on chemoresponse communities. Taken together, our method, as well as the accompanying database, improved the performance of classifiers for drug resistance and provided novel model to uncover the possible regulatory mechanism of individual response to drug. This article is protected by copyright. All rights reserved.

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Efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

Abstract

Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3). Sixteen eligible trials with 4031 patients were included. Addition of anti-EGFR regimens to standard therapy significantly improved OS of patients with HNSCC (HR = 0.89; 95% CI, 0.82–0.96), with a moderately elevated rate of SAEs (RR = 1.08; 95% CI, 1.03–1.13). Subgroup analysis indicated that the survival benefit was observed when cetuximab was administered concurrently with radiotherapy (RT) for stage III/IV patients (HR = 0.76; 95% CI, 0.61–0.94; P = 0.01), or with chemotherapy for recurrent or metastatic (R/M) HNSCC (HR = 0.86; 95% CI, 0.78–0.95; P = 0.005). Significantly increased ORR (RR = 1.51; 95% CI 1.05–2.18) and PFS (HR = 0.72; 95% CI, 0.59–0.88) were found in R/M HNSCC patients treated with anti-EGFR plus chemotherapy, while no significant improvements were found in stage III/IV patients treated with anti-EGFR plus standard therapy. In conclusion, addition of cetuximab to standard therapy may improve outcomes for R/M HNSCC patients, while causing a moderate increase in SAEs. For stage III/IV patients, anti-EGFR mAb plus RT can improve OS compared with RT alone, while replacement of chemotherapy with EGFR mAb or adding EGFR mAb to combined chemotherapy and RT did not improve outcomes. This article is protected by copyright. All rights reserved.

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Intraductal papillary mucinous neoplasm of the pancreas rapidly xenografts in chicken eggs and predicts aggressiveness

Abstract

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology and marker expression. Of the IPMN tissues transplanted into eggs, 63% formed tumor xenografts within 4 days, while none of the 12 IPMN tissues transplanted into immunodeficient mice engrafted. In the eggs, the grafting efficiency of high-grade (n=14) and intermediate-grade (n=17) dysplasia was 77% and was significantly higher than the 39% grafting efficiency of low-grade dysplasia (n=18). According to mucinous expression, 46 IPMN tissues were classified into gastric (n=6), intestinal (n=3), oncocytic (n=23), and pancreatobiliary (n=14) subtypes. The grafting efficiency was highest for the pancreatobiliary subtype (86%), followed by the oncocytic (70%), gastric (33%) and intestinal (33%) subtypes. The morphology and expression patterns of mucins, progression markers and pancreatic ductal markers were comparable between the primary IPMN tissues and their xenograft copies. The individual tumor environment was largely maintained during subtransplantation, as evaluated upon passage 6. This new IPMN model may facilitate experimental studies and treatment decisions for the optimal personalized management of IPMN. This article is protected by copyright. All rights reserved.

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Anaplastic Lymphoma Kinase Testing: IHC vs. FISH vs. NGS

Opinion statement

Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4–7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin. The selection of patients based on their ALK status is vital on account of the high response rates with the ALK-targeted agents in this subset of patients. Standardization and validation of ALK rearrangement detection methods is essential for accurate and reproducible results. There are currently three detection methods widely available in clinical practice, including fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and polymerase chain reaction (PCR)-based next generation sequencing (NGS) technology. However, the choice of diagnostic methodology for ALK rearrangement detection in clinical practice remains a matter of debate. With accumulating data enumerating the advantages and disadvantages of each of the three methods, combining more than one testing method for ALK fusion detection may be beneficial for patients. In this review, we will discuss the current methods used in ALK rearrangement detection with emphasis on their key advantages and disadvantages.

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The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer

Opinion statement

Approximately 20% of patients with cancer of the stomach or gastro-oesophageal junction (GOJ) present with resectable disease. Long-term outcome after surgery alone in these patients is poor, and a combined treatment approach is the standard of care. The two approaches to managing patients with cancer of the GOJ are perioperative chemotherapy or preoperative chemoradiotherapy. Based upon the most recent evidence, patients treated with a perioperative approach and deemed suitable for a triplet regimen should be considered for pre- and post-operative FLOT (5-fluorouracil [5-FU], leucovorin, oxaliplatin and docetaxel) and those suitable for a doublet regimen should be considered for a fluoropyrimidine/platinum combination such as capecitabine and oxaliplatin. Alternatively, such patients may be considered for preoperative chemoradiotherapy according to the CROSS regimen. True gastric cancers may be treated with a perioperative approach or, as is commonly used in Asia, postoperative adjuvant chemotherapy.

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Update in the Therapy of Advanced Neuroendocrine Tumors

Opinion statement

Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of ~ 6.9/100,000. NETs arise throughout the body from cells of the diffuse endocrine system. More than half originate from endocrine cells of the gastrointestinal tract and the pancreas, thus being referred to as gastroenteropancreatic NETs (GEP-NETs). The only treatment that offers a cure is surgery; however, most patients are diagnosed with metastatic disease, and curative surgery is usually not an option. These patients can be offered long-term systemic treatment, for both symptomatic relief and tumor growth suppression. Evidence-based treatment options include somatostatin analogs, everolimus (a mTOR inhibitor), sunitinib (a tyrosine kinase inhibitor), and peptide receptor radionuclide therapy, alone or combined with cytoreductive procedures (surgery or liver-directed procedures). Other treatment options being investigated are immunotherapy and epigenetic assessment that may lead to more personalized interventions. We believe that each patient should be thoroughly evaluated and their case discussed by a multidisciplinary team that is up-to-date with all treatment modalities including ongoing clinical trials, before selecting the proper treatment option.

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Diagnosis and Treatment of Aplastic Anemia

Opinion statement

Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of early hematopoietic cells. Diagnosis of AA requires a comprehensive approach with prompt evaluation for inherited and secondary causes of bone marrow aplasia, while providing aggressive supportive care. The choice of frontline therapy is determined by a number of factors including AA severity, age of the patient, donor availability, and access to optimal therapies. For newly diagnosed severe aplastic anemia, bone marrow transplant should be pursued in all pediatric patients and in younger adult patients when a matched sibling donor is available. Frontline therapy in older adult patients and in all patients lacking a matched sibling donor involves immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporine A. Recent improvements in upfront therapy include encouraging results with closely matched unrelated donor transplants in younger patients and the emerging benefits of eltrombopag combined with initial IST, with randomized studies underway. In the refractory setting, several therapeutic options exist, with improving outcomes of matched unrelated donor and haploidentical bone marrow transplantation as well as the addition of eltrombopag to the non-transplant AA armamentarium. With the recent appreciation of frequent clonal hematopoiesis in AA patients and with the growing use of next-generation sequencing in the clinic, utmost caution should be exercised in interpreting the significance of somatic mutations in AA. Future longitudinal studies of large numbers of patients are needed to determine the prognostic significance of somatic mutations and to guide optimal surveillance and treatment approaches to prevent long-term clonal complications.

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The Multidisciplinary Approach to Localized Pancreatic Adenocarcinoma

Opinion statement

Pancreatic adenocarcinoma 2030 (PCa) is predicted to be the second leading cause of cancer death in USA by 2030. To date, attempts at early detection have been unsuccessful. Therapies for resectable PCa include surgery followed by adjuvant chemotherapy with or without radiotherapy. Unfortunately, most patients with PCa present with advanced disease and thus only 20% of patients are potentially resectable upon presentation. Improved surgical techniques along with adjuvant combination chemotherapy have improved outcomes for patients with resectable disease. The optimal treatment approach for borderline resectable and locally advanced unresectable PCa has not yet been defined. Despite significant advances in the palliative treatment of PCa, long-term survival of early stage disease continues to be sobering. The key to improving outcomes for this largely fatal disease is to identify multidisciplinary therapeutic interventions including surgical, medical, and radiation techniques tailored to the patient and their disease characteristics. The neoadjuvant approach provides an in vivo platform to test novel treatment options to help us understand tumor biology and surrounding microenvironment, which may ultimately help us achieve the goal of improvement in long-term survival. While the neoadjuvant approach remains popular as a way to optimally select patients that might benefit most from surgery, randomized trials utilizing adjuvant and neoadjuvant novel therapies hold the key to truly personalizing the ideal treatment strategy for localized PCa.

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Clinical and Radiologic Outcomes of Submerged and Nonsubmerged Bone-Level Implants with Internal Hexagonal Connections in Immediate Implantation: A 5-Year Retrospective Study

Abstract

Purpose: To evaluate the 5-year clinical and radiologic outcome of immediate implantation using submerged and nonsubmerged techniques with bone-level implants and internal hexagonal connections and the effects of potential influencing factors.

Materials and Methods: A total of 114 bone-level implants (XiVE S plus) with internal hexagonal connections inserted into 72 patients were included. Patients were followed up for 5 years. A t-test was used to statistically evaluate the marginal bone loss between the submerged and nonsubmerged groups. The cumulative survival rate (CSR) was calculated according to the life table method and illustrated with Kaplan-Meier survival curves. Comparisons of the CSR between healing protocols, guided bone regeneration, implants with different sites, lengths, and diameters were performed using log-rank tests.

Results: The 5-year cumulative implant survival rates with submerged and nonsubmerged healing were 94% and 96%, respectively. No statistically significant differences in terms of marginal bone loss, healing protocol, application of guided bone regeneration, implant site, or length were observed.

Conclusions: High CSRs and good marginal bone levels were achieved 5 years after immediate implantation of bone-level implants with internal hexagonal connections using both the submerged and nonsubmerged techniques. Factors such as implant length, site, and application of guided bone regeneration did not have an impact on the long-term success of the implants.

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Marginal Fit Comparison of CAD/CAM Crowns Milled from Two Different Materials

Abstract

Purpose

To evaluate the marginal fit of CAD/CAM copings milled from hybrid ceramic (Vita Enamic) blocks and lithium disilicate (IPS e.max CAD) blocks, and to evaluate the effect of crystallization firing on the marginal fit of lithium disilicate copings.

Materials and Methods

A standardized metal die with a 1-mm-wide shoulder finish line was imaged using the CEREC AC Bluecam. The coping was designed using CEREC 3 software. The design was used to fabricate 15 lithium disilicate and 15 hybrid ceramic copings. Design and milling were accomplished by one operator. The copings were seated on the metal die using a pressure clamp with a uniform pressure of 5.5 lbs. A Macroview Microscope (14×) was used for direct viewing of the marginal gap. Four areas were imaged on each coping (buccal, distal, lingual, mesial). Image analysis software was used to measure the marginal gaps in μm at 15 randomly selected points on each of the four surfaces. A total of 60 measurements were made per specimen. For lithium disilicate copings the measurements for marginal gap were made before and after crystallization firing. Data were analyzed using paired t-test and Kruskal-Wallis test.

Results

The overall mean difference in marginal gap between the hybrid ceramic and crystallized lithium disilicate copings was statistically significant (p < 0.01). Greater mean marginal gaps were measured for crystallized lithium disilicate copings. The overall mean difference in marginal gap before and after firing (precrystallized and crystallized lithium disilicate copings) showed an average of 62 μm increase in marginal gap after firing. This difference was also significant (p < 0.01).

Conclusions

A significant difference exists in the marginal gap discrepancy when comparing hybrid ceramic and lithium disilicate CAD/CAM crowns. Also crystallization firing can result in a significant increase in the marginal gap of lithium disilicate CAD/CAM crowns.

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Evaluation of Immediate Implants Augmented with Autogenous Bone/Melatonin Composite Graft in the Esthetic Zone: A Randomized Controlled Trial

Abstract

Purpose

To evaluate the clinical and radiographic outcomes following the application of autogenous bone (ABG)/melatonin composite graft around immediate implants in the esthetic zone compared to ABG alone.

Materials and Methods

Twenty-six patients with two nonrestorable anterior/premolar teeth were randomly classified into two equal groups. Dental implants were immediately inserted either with ABG (control group) or ABG/melatonin (test group). Outcome measures were peri-implant sulcus depth (PD), gingival index (GI), and wound healing scores. Cone beam computed tomography (CBCT) was recorded at baseline, 6, and 9 months.

Results

At the end of the study, a significant difference was shown in the mean of marginal bone loss between the control group (1.91 mm ± 0.42) and the test group (0.84 mm ± 0.34) at p = 0.0001. The test group showed a significant gain in bone density, 500.73 ± 40.92, versus 420.14 ± 38.33 in the control group (p = 0.0001). There was a statistically significant difference between the control group (0.68 ± 0.42) versus the test group (0.45 ± 0.49; p = 0.044) in GI. PD was significantly reduced at the end of the study in the test group (0.42 mm ± 0.50; p = 0.002), with a similar significant improvement in the healing scores (p = 0.026).

Conclusion

Within the limitations of this study, immediate implants augmented with ABG/melatonin composite graft would be a valuable option in the esthetic zone.

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Effect of Distal Implant Inclination on Dislodging Forces of Different Locator Attachments Used for Mandibular Overdentures: An In Vitro Study

Abstract

Purpose

To evaluate the effect of distal implant inclination on axial and nonaxial retentive forces of different Locator attachments used to retain mandibular overdentures.

Materials and methods

Four duplicate mandibular edentulous acrylic models received 2 implants in the canine areas with 0°, 5°, 10°, and 20° distal inclinations. Experimental overdentures were connected to the implants with Locator extra light retention (Le), Locator light retention (Ll), and Locator medium retention (Lm). For the 20° model, extended range Locator extra-light retention (Lee) and Locator medium retention (Lem) were used. Axial and nonaxial (anterior, posterior, lateral) retentive forces were measured initially and after 540 cycles of denture insertion and removal. Three-way mixed ANOVA was used to analyze axial and nonaxial retentive forces

Results

After wear simulation, 20° angulation showed the highest axial retention for Le and Ll while 5° showed the highest retention for Lm; 0° and 5° showed the highest anterior and posterior retention for Lm; 20° showed the highest lateral retention for Le and Ll. For all implant inclinations, Lm showed the highest axial and nonaxial retention, and Le and Lee showed the lowest retention for 10° and 20° inclined implants, respectively.

Conclusions

Axial and nonaxial retention of Locator attachments for implant-retained overdentures are significantly affected by the degree of distal implant inclination and the type of nylon inserts. Lm is recommended to retain overdentures when implants have 5° or 10° distal inclination, and Le and Ll are recommended with 20° inclination to maintain high axial and nonaxial retention after wear.

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An All-Zirconia Crown Discovered 2 Years Following Aspiration

Abstract

Accidental aspiration or ingestion can occur in dental treatment, as most procedures are performed with the patient in a supine position or semi-recumbent position. Aspiration of foreign bodies commonly causes acute symptoms such as violent coughing, choking, and dyspnea; however, if foreign bodies are stuck distally to the lower lobe bronchi or the bronchus intermedius, acute presentation can be rare. This clinical report documents a 68-year-old male patient who accidentally aspirated an all-zirconia crown during the try-in procedure. The case was initially surmised as ingestion. The crown remained in the lower lobe of the left lung for about 2 years without any significant symptoms. This report cautions the importance of airway protection during dental procedures.

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In Vitro Assessment of Retention and Resistance Failure Loads of Teeth Restored with a Complete Coverage Restoration and Different Core Materials

Abstract

Purpose

To investigate in vitro the retention and the resistance form, as well as the failure modes of maxillary premolars restored with cast metal crowns and different core materials.

Materials and Methods

Sixty human extracted maxillary premolars were selected according to their size and were embedded in PMMA resin blocks. After removing a part of their clinical crowns, the teeth were randomly divided into 3 groups of 20 teeth and were either left unrestored, or they were restored with amalgam or composite resin. All teeth were prepared for a cast metal complete coverage restoration. The restorations were cemented on the prepared teeth with a resin-modified glass ionomer luting agent (GC Fuji Plus). All specimens were subjected to static loading at 1 mm/min by a universal testing machine, until failure. Half the specimens of each group were subjected to tensile loading along the long axis of the teeth. The other half were subjected to compressive loading at a 30° angle. Failure loads and failure modes for each tooth were recorded. The statistical analysis included descriptive statistics, one-way ANOVA, and Tukey's HSD test.

Results

One-way ANOVA revealed statistically significant differences among the 3 tested groups (p < 0.05) for both tests. The group of teeth with no core material presented the highest failure loads for both the tensile and the compressive loading tests, with mean loads of 381.02 Ν and 741.21 Ν, respectively. Mean tensile and compressive failure loads for the amalgam group were 277.34 Ν and 584.75 Ν, while the composite resin group presented the lowest tensile and compressive failure values, which were 250.77 Ν and 465.78 Ν, respectively. The compression loading test resulted in the same failure mode for all specimens, which included unfavorable fracture of the teeth in combination with detachment of the cast metal complete coverage restorations. The tensile loading test resulted in different failure modes between the groups that used a core material and the group with no core material.

Conclusions

Teeth that lost more than half of their coronal structure presented better retention and resistance form if no core material was used, provided that a minimum of 2-mm axial wall height was present at the missing part. Teeth that have lost more than half of their coronal structure and were restored with amalgam core presented better retention and resistance form than those restored with composite resin. Catastrophic fractures, extending to the root, were associated with compression forces but not with tensile forces.

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Short-term changes in chewing efficiency and subjective evaluation in normal dentate subjects after insertion of oral appliances with an occlusal flat table

Summary

Background

Oral appliances with an occlusal flat table are used as treatment dentures. However, the short-term effect of insertion of such oral appliances on chewing has not been reported.

Objective

This study aimed to determine whether experimental and continuous insertion of oral appliances with an occlusal flat table has an effect on chewing efficiency and Oral Health Impact Profile (OHIP) in healthy participants.

Methods

Ten participants each in the oral-appliance and control (no oral-appliance insertion) groups attended six data collection sessions for 5 consecutive days. Participants answered the OHIP questionnaire and underwent the chewing efficiency test. For each parameter, intergroup differences were investigated in terms of change from baseline to immediately after oral-appliance insertion (0 h; p < 0.05) and from 0 h to 24, 48, 72, and 96 h after oral-appliance insertion (p < 0.05).

Results

There were significant differences between groups in the degree of change in chewing efficiency and OHIP scores for functional limitation, physical pain, physical disability, and handicap from baseline to 0 h (all, p < 0.001); among these, only OHIP scores for functional limitation and physical pain demonstrated significant differences in degree of change between the two groups at 96 h after appliance insertion (p = 0.477 and 0.275, respectively). Differences between the two groups in the degree of change in other parameters were not significant.

Conclusion

Insertion of oral appliances caused a decrease in chewing efficiency and an increase in OHIP scores. Continuous insertion improved functional limitation and physical pain within 96 h.

This article is protected by copyright. All rights reserved.

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Decisional regret and choice of breast reconstruction following mastectomy for breast cancer: A systematic review

Abstract

Objective

Women facing mastectomy for breast cancer should have the option of considering whether they would like breast reconstruction (BR), and if so, what type and when. Previous research has demonstrated some women will come to regret their decision about BR. We aim to summarise the evidence about the prevalence of decisional regret (DR) associated with BR choices and identify factors influencing vulnerability to DR.

Methods

A systematic review of the literature reporting BR-related DR published between January 1994 and February 2017 identified 254 initial search results. Thirteen publications from 12 studies (5,672 participants) met the selection criteria and were included in the final review. Each article was allocated a quality score out of 24.

Results

Overall, DR levels were reported as low and stable, although direct comparison across studies was limited by inconsistencies in measurement and reporting methods. Estimates of DR scores ranged from 9.3/100 to 5.4/20. All studies identified a relationship between higher levels of DR and an insufficient amount, inadequate quality or unclear nature of information provided to women prior to undergoing mastectomy. A major determinant of DR was new or recurrent cancer, while psychosocial characteristics including depression, distress and negative body image increased the likelihood of DR.

Conclusion

The available research is yet to provide a clear understanding of the many inter-related issues involved in DR. Given the consensus that pre-surgical information was inadequate, making standardised educational material more widely available and increasing use of breast care nurses in pre-operative patient education roles may be useful.

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Insufficienza velofaringea

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): F. Marmouset, A.G. Piller, C. Bobillier, S. Pondaven, E. Lescanne
Lo sfintere velofaringeo è formato dai muscoli velari e della parete faringea posteriore. Il suo ruolo è importante nella differenziazione fonemica e nella deglutizione. La lesione della funzione dello sfintere velofaringeo è multicausale e può rivelare una patologia cromosomica come la sindrome 22q11.2. Un'insufficienza velofaringea presente nel periodo di apprendimento, nel bambino piccolo, può causare delle conseguenze permanenti sulla parola e sull'immagine di sé. La gestione diagnostica e il bilancio preterapeutico sono necessariamente multidisciplinari. Il chirurgo ORL realizza un bilancio morfologico e funzionale mediante rinofibroscopia e diagnostica per immagini, determinando l'operabilità. Il bilancio ortofonico-foniatrico è funzionale e percettivo, differenziando l'ipernasalità dalle compensazioni inadeguate e quantificando l'insufficienza velofaringea. Nel bambino è necessario un piano terapeutico multidisciplinare a lungo termine. Il chirurgo ORL mira a ripristinare una chiusura velare con l'obiettivo di migliorare l'ipernasalità (risonanza) e la perdita nasale (perdita d'aria). L'ortofonista si dedica preferibilmente alla gestione dei meccanismi di compenso articolatori inadeguati, pur avendo un'azione sullo sfintere velofaringeo. Un sostegno e una guida familiare sono indispensabili nel bambino piccolo e altri professionisti partecipano spesso alla gestione.



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Melanomi cutanei cervicofacciali

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): A. Moya-Plana, E. Routier, C. Mateus, F. Kolb, C. Robert
I melanomi maligni cervicofacciali devono essere divisi in due gruppi distinti: i melanomi di origine cutanea e i melanomi mucosi. In effetti, queste due entità presentano importanti differenze in termini di storia naturale, epidemiologia, gestione terapeutica e prognosi. Il melanoma cutaneo è la forma predominante. La sua incidenza è in costante aumento da diversi decenni, con, in Francia, dieci nuovi casi ogni 100 000 abitanti per anno (all'origine di 1 600 decessi). Il principale fattore di rischio è l'esposizione solare, mentre le forme familiari rappresentano solo il 10% dei pazienti. Nel 30% dei casi, la localizzazione è cervicofacciale. Le particolarità anatomiche di questa regione influenzano significativamente le modalità di trattamento e la prognosi di questi pazienti, che è più riservata. Benché il trattamento resti prima di tutto chirurgico, sono stati compiuti recentemente notevoli progressi nel trattamento degli stadi avanzati con lo sviluppo di terapie mirate (anti-BRAF in particolare) e dell'immunoterapia (anti-programmed death 1 [PD-1]). Un posto importante deve essere lasciato alla prevenzione primaria e all'educazione dei pazienti, soprattutto in termini di protezione solare. Il melanoma mucoso, dal canto suo, è un tumore raro che rappresenta meno del 5% di tutti i melanomi. La sua localizzazione preferenziale è cervicofacciale, in particolare a livello nasosinusale. La prognosi del melanoma mucoso è riservata. Questa patologia è difficile da controllare a livello locale a causa del suo carattere spesso multifocale e dei vincoli anatomici della regione cervicofacciale, che rendono difficile ottenere un'exeresi oncologica soddisfacente. Inoltre, esiste un significativo rischio metastatico all'origine di un'importante mortalità precoce. Il trattamento di riferimento è la chirurgia, classicamente seguita da una radioterapia adiuvante. Nuove tecniche di radioterapia (adroterapia, ecc.) e terapie innovative (terapie mirate, ecc.) sono in corso di valutazione.



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Melanomi mucosi cervicofacciali

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): A. Moya-Plana, J. Thariat, N. Saroul, O. Casiraghi, S. Vergez, L. de Gabory, F. Janot
I melanomi maligni cervicofacciali devono essere divisi in due gruppi distinti: i melanomi di origine cutanea e i melanomi mucosi. In effetti, queste due entità presentano importanti differenze in termini di storia naturale, epidemiologia, gestione terapeutica e prognosi. Il melanoma cutaneo è la forma predominante. La sua incidenza è in costante aumento da diversi decenni, con dieci nuovi casi in Francia per 100 000 abitanti e per anno (all'origine di 1 600 decessi). Il principale fattore di rischio è l'esposizione al sole, mentre le forme familiari rappresentano solo il 10% dei pazienti. Nel 30% dei casi, la localizzazione è cervicofacciale. Le particolarità anatomiche di questa regione influenzano significativamente le modalità terapeutiche e la prognosi di questi pazienti, che è più riservata. Benché il trattamento resti prima di tutto chirurgico, sono stati compiuti recentemente progressi importanti nel trattamento degli stadi avanzati con lo sviluppo delle terapie mirate (in particolare, anti-BRAF) e dell'immunoterapia (anti-PD1). Un posto importante deve essere attribuito alla prevenzione primaria e all'educazione dei pazienti, soprattutto in termini di protezione solare. Il melanoma mucoso, dal canto suo, è un tumore raro che rappresenta meno del 5% di tutti i melanomi. La sua localizzazione preferenziale è cervicofacciale, in particolare a livello nasosinusale. La prognosi del melanoma mucoso è riservata. In effetti, questa patologia è difficile da controllare localmente a causa del suo carattere spesso multifocale e dei vincoli anatomici della regione cervicofacciale, che rendono difficile la realizzazione di un'exeresi oncologica soddisfacente. Inoltre, c'è un significativo rischio metastatico all'origine di una significativa mortalità precoce. Il trattamento di riferimento è la chirurgia tipicamente seguita da una radioterapia adiuvante. Nuove tecniche di irradiazione (adroterapia, ecc.) e terapie innovative (terapie mirate, ecc.) sono in corso di valutazione.



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