Sunday, November 1, 2020

Esophageal sponge sampling: a promising approach for early detection of esophageal cancer

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Esophageal sponge sampling: a promising approach for early detection of esophageal cancer in Africa's high-incidence region.

Int J Cancer. 2020 Oct 31;:

Authors: Buckle GC

PMID: 33128772 [PubMed - as supplied by publisher]

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Minimally invasive oesophageal sponge cytology sampling

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Minimally invasive oesophageal sponge cytology sampling is feasible in a Tanzanian community setting.

Int J Cancer. 2020 Oct 31;:

Authors: Middleton DRS, Mmbaga BT, O'Donovan M, Abedi-Ardekani B, Debiram-Beecham I, Nyakunga-Maro G, Maro V, Bromwich M, Daudi A, Ngowi T, Minde R, Claver J, Mremi A, Mwasamwaja A, Schüz J, Fitzgerald RC, McCormack V

Abstract
Oesophageal sponge cytology is an endoscopy alternative well accepted by patients with extensive data for accuracy in the context of adenocarcinoma. Few studies have assessed its feasibility in asymptomatic community members, and fewer still in East Africa, where oesophageal squamous cell carcinoma (ESCC) rates are high. We aimed to assess the feasibility of a capsule-based diagnosis of oesophageal squamous dysplasia (ESD), an ESCC precursor, which may benefit epidemiological and early detection research. We collected Cytosponge™ collections in 102 asymptomatic adults from Kilimanjaro, Tanzania. Uptake, acceptability and safety were assessed. Participants scored acceptability immediately following the procedure and 7 days later on a scale of 0 (least) to 10 (most acceptable). Slides from paraffin embedded cell clots were read by two pathologists for ESD and other pathologies. All participants (52 men, 50 women, aged 30-77) swallowed the device at first attempt, 100 (98%) of which gave slides of adequate cellularity. Acceptability scores were 10 (53%), 9 (24%), 8 (21%), 7 (2%) and 6 (1%), with no differences by age, sex, or time of asking. Cytological findings were: oesophageal inflammation (4%), atypical squamous cells of uncertain significance (1%), low grade dysplasia (1%), gastritis (22%) and suspected intestinal metaplasia (6%). Setting-specific logistical and ethical considerations of study implementation are discussed. We demonstrate the safety, acceptability and feasibility of Cytosponge sampling in this setting, paving the way for innovative aetiology and early-detection research. Targeted sampling strategies and biomarker development will underpin the success of such initiatives. The study protocol is registered on ClinicalTrials.gov (NCT04090554) This article is protected by copyright. All rights reserved.

PMID: 33128785 [PubMed - as supplied by publisher]

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The Notch Ligand Jagged1 is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea.

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The Notch Ligand Jagged1 is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea.

J Neurosci. 2020 Oct 30;:

Authors: Chrysostomou E, Zhou L, Darcy YL, Graves KA, Doetzlhofer A, Cox BC

Abstract
During cochlear development, the Notch ligand JAGGED 1 (JAG1) plays an important role in the specification of the prosensory region, which gives rise to sound-sensing hair cells and neighboring supporting cells (SCs). While JAG1's expression is maintained in SCs through adulthood, the function of JAG1 in SC development is unknown. Here, we demonstrate that JAG1 is essential for the formation and maintenance of Hensen's cells, a highly specialized SC-subtype located at the edge of the auditory epithelium. Using Sox2CreER/+ ::Jag1loxP/loxP mice of both genders, we show that Jag1 deletion at the onset of differentiation, at embryonic day 14.5, disrupted Hensen's cell formation. Similar loss of Hensen's cells was observed when Jag1 was deleted after Hensen's cell formation at postnatal day (P) 0/P1 and fate-mapping analysis revealed that in the absence of Jag1, some Hensen's cells die, but others convert into neighboring Claudius cells. In support of a role for JAG1 in cell survi val, genes involved in mitochondrial function and protein synthesis were downregulated in the sensory epithelium of P0 cochlea lacking Jag1 Finally, using Fgfr3-iCreERT2 ::Jag1loxP/loxP mice to delete Jag1 at P0, we observed a similar loss of Hensen's cells and found that adult Jag1 mutant mice have hearing deficits at the low frequency range.SIGNIFICANCE STATEMENT:Hensen's cells play an essential role in the development and homeostasis of the cochlea. Defects in the biophysical or functional properties of Hensen's cells have been linked to auditory dysfunction and hearing loss. Despite their importance, surprisingly little is known about the molecular mechanisms that guide their development. Morphological and fate-mapping analyses in our study revealed that in the absence of the Notch ligand JAGGED1, Hensen's cells died or converted into Claudius cells, which are specialized epithelial-like cells outside the sensory epithelium. Confirming a link between JAGGED1 and cell survival, t ranscriptional profiling showed that JAGGED1 maintains genes critical for mitochondrial function and tissue homeostasis. Finally, auditory phenotyping revealed that JAGGED1's function in supporting cells is necessary for low frequency hearing.

PMID: 33127852 [PubMed - as supplied by publisher]

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Principles of Intramural Surgery.

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Principles of Intramural Surgery.

Surg Clin North Am. 2020 Dec;100(6):1169-1182

Authors: Tat C, Barajas-Gamboa JS, Kroh M

Abstract
Intramural surgery is a minimally invasive surgical technique based on flexible endoscopy. The first step involves the initial mucosal incision for entry point. Then a submucosal tunnel is dissected to the site of the target anatomy. The procedure performed may include myotomy or lesion removal. When complete, the initial mucosal incision is closed. This technique separates the mucosal flap from the surgical site, minimizing the risk of full-thickness perforation and gastrointestinal leakage. Peroral endoscopic myotomy is the most studied application of intramural surgery but other procedures have emerged. This article explores principles of intramural surgery and summarizes its applications.

PMID: 33128886 [PubMed - as supplied by publisher]

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Peroral Esophageal Myotomy.

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Peroral Esophageal Myotomy.

Surg Clin North Am. 2020 Dec;100(6):1183-1192

Authors: Drexel S, Kishawi S, Marks J

Abstract
Achalasia is a neurodegenerative disorder of the lower esophagus characterized by high lower esophageal pressures and aperistalsis of the esophageal body. It remains a difficult to treat disease with significant burden on patients due to difficulty swallowing leading to malnutrition. Peroral endoscopic myotomy (POEM) is a newer endoscopic treatment of achalasia. It involves dividing the muscular layer of the esophagus through a submucosal tunnel. Ten-year data show POEM is a safe and effective treatment of achalasia. However, postoperative gastroesophageal reflux disease remains an important consideration.

PMID: 33128887 [PubMed - as supplied by publisher]

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Disentangling EEG responses to TMS due to cortical and peripheral activations.

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Disentangling EEG responses to TMS due to cortical and peripheral activations.

Brain Stimul. 2020 Oct 27;:

Authors: Rocchi L, Di Santo A, Brown K, Pereda JI, Casula E, Rawji V, Di Lazzaro V, Koch G, Rothwell J

Abstract
BACKGROUND: the use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP).
OBJECTIVE/HYPOTHESIS: to measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1).
METHODS: 19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation.
RESULTS: auditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms.
CONCLUSIONS: if careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by non-specific, late (100-200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used.

PMID: 33127580 [PubMed - as supplied by publisher]

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The Lost Airway.

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The Lost Airway.

Anesthesiol Clin. 2020 Dec;38(4):875-888

Authors: Potnuru P, Artime CA, Hagberg CA

Abstract
Management of the unanticipated difficult airway is one of the most relevant and challenging crisis management scenarios encountered in clinical anesthesia practice. Several guidelines and approaches have been developed to assist clinicians in navigating this high-acuity scenario. In the most serious cases, the clinician may encounter a failed airway that results from failure to ventilate an anesthetized patient via facemask or supraglottic airway or intubate the patient with an endotracheal tube. This dreaded cannot intubate, cannot oxygenate situation necessitates emergency invasive access. This article reviews the incidence, management, and complications of the failed airway and training issues related to its management.

PMID: 33127033 [PubMed - as supplied by publisher]

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Prospective phase II study of radiotherapy dose and volume de-escalation for elective neck treatment of oropharyngeal and laryngeal cancer.

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Via Larynx
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Prospective phase II study of radiotherapy dose and volume de-escalation for elective neck treatment of oropharyngeal and laryngeal cancer.

Int J Radiat Oncol Biol Phys. 2020 Oct 27;:

Authors: Sher DJ, Pham NL, Shah JL, Sen N, Williams KA, Subramaniam RM, Moore W, Chorley R, Ahn C, Khan SM

Abstract
PURPOSE: The required elective nodal dose and volumes for head and neck intensity-modulated radiotherapy (IMRT) have largely been extrapolated from conventional radiotherapy fields. In this prospective, dual-center, phase II study, we investigated the efficacy and tolerability of reduced elective nodal volume and dose in oropharyngeal and laryngeal squamous cell carcinoma (SqCC).
MATERIALS/METHODS: Patients with newly-diagnosed SqCC of the oropharynx and larynx were eligible for enrollment. Each lymph node was characterized as involved or suspicious based on imaging criteria. For oropharynx cancer, only involved and immediately adjacent stations were treated to 40 Gy in 20 fractions. In larynx patients, at least bilateral levels II and III were treated to 40 Gy, with level IV treated only if level III was involved. Involved and suspicious nodes were then boosted with 30 Gy and 24 Gy in 15 fractions, respectively. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was solitary elective volume recurrence, with secondary endpoints including patterns-of-failure and patient reported outcomes (PROs).
RESULTS: A total of 72 (51 oropharynx, 21 larynx) patients completed treatment on this trial from January 2017 through November 2018. The stages at presentations were 5, 17, and 50 stage I-II, III, and IV, respectively, with 90% treated with chemoradiotherapy. At a median follow-up of 24.7 months for surviving patients, there have been no solitary elective nodal recurrences. Seven patients developed a nodal recurrence, five of which were in-field and two were elective with synchronous in-field recurrence. PRO assessment at 1 year showed superior or equivalent outcomes to baseline except for saliva and taste measures.
CONCLUSION: The results of this trial suggest that elective dose and volume reduction is oncologically sound for oropharyngeal and laryngeal cancer treated with IMRT, with promising quality-of-life outcomes.

PMID: 33127491 [PubMed - as supplied by publisher]

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Embryonal rhabdomyosarcoma masquerading as a left vocal cord granuloma.

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Via Larynx
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Embryonal rhabdomyosarcoma masquerading as a left vocal cord granuloma.

BMJ Case Rep. 2020 Oct 30;13(10):

Authors: Linton S, Stapleton E, Penney S, Sharma MP

Abstract
Embryonal rhabdomyosarcoma (ERMS) of the larynx in adults is an extremely rare diagnosis with insidious onset and progression. Only six reports (including this one) have been documented in the literature. Clinical presentation is dependent on the site, size, subtype of ERMS and growth rate. Hoarseness is the usual first symptom, followed by stridor and dyspnoea, with dysphagia being late in onset. Accurate staging and risk stratification is necessary to avoid overtreating/undertreating patients and should be guided by local Head and Neck/Sarcoma Multidisciplinary Teams. Treatment has moved away from radical therapeutic regimens to less-invasive, organ-preserving therapies. Long-term follow-up is required due to the risk of late recurrence.

PMID: 33127702 [PubMed - as supplied by publisher]

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Strong oral plaque microbiome signatures for dental implant diseases identified by strain-resolution metagenomics.

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Strong oral plaque microbiome signatures for dental implant diseases identified by strain-resolution metagenomics.

NPJ Biofilms Microbiomes. 2020 Oct 30;6(1):47

Authors: Ghensi P, Manghi P, Zolfo M, Armanini F, Pasolli E, Bolzan M, Bertelle A, Dell'Acqua F, Dellasega E, Waldner R, Tessarolo F, Tomasi C, Segata N

Abstract
Dental implants are installed in an increasing number of patients. Mucositis and peri-implantitis are common microbial-biofilm-associated diseases affecting the tissues that surround the dental implant and are a major medical and socioeconomic burden. By metagenomic sequencing of the plaque microbiome in different peri-implant health and disease conditions (113 samples from 72 individuals), we found microbial signatures for peri-implantitis and mucositis and defined the peri-implantitis-related complex (PiRC) composed by the 7 most discriminative bacteria. The peri-implantitis microbiome is site specific as contralateral healthy sites resembled more the microbiome of healthy implants, while mucositis was specifically enriched for Fusobacterium nucleatum acting as a keystone colonizer. Microbiome-based machine learning showed high diagnostic and prognostic power for peri-implant diseases and strain-level profiling identified a previously uncharacterized subspecies of F. nuclea tum to be particularly associated with disease. Altogether, we associated the plaque microbiome with peri-implant diseases and identified microbial signatures of disease severity.

PMID: 33127901 [PubMed - as supplied by publisher]

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Mucinous cystadenocarcinoma of the oral tongue: malignant transformation from a mucinous cystadenoma?

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Mucinous cystadenocarcinoma of the oral tongue: malignant transformation from a mucinous cystadenoma?

BMJ Case Rep. 2020 Oct 30;13(10):

Authors: Dutra S, Rito M, Vilares M, Borges A

Abstract
Mucinous cystadenocarcinoma of minor salivary glands is an extremely rare entity that has only recently been described, with a few published cases in the English literature. A 42-year-old woman with a history of a surgically excised mucinous cystadenoma of the oral tongue, presented with a painful swelling in the oral tongue slowly growing for 1 month. On clinical examination, there was a firm, relatively well-circumscribed mass in the left posterior border of the mobile tongue. Subsequent MRI scan revealed a heterogeneous lesion composed of multiple cysts separated by contrast enhancing septa, in the posterior two-thirds of the left tongue. Imaging findings were similar to those of the previously resected mass, suggesting local relapse of the primary lesion. A complete surgical excision was performed and the histopathological examination revealed typical features of a low-grade mucinous cystadenocarcinoma of minor salivary glands.

PMID: 33127690 [PubMed - as supplied by publisher]

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