Evidence for the approach to the diagnostic evaluation of squamous cell carcinoma occult primary tumors of the head and neck

Publication date: January 2019

Source: Oral Oncology, Volume 88

Author(s): Pawel Golusinski, Pasquale Di Maio, Berrin Pehlivan, Steve Colley, Paul Nankivell, Anthony Kong, Andrew Hartley, Hisham Mehanna

Abstract

Metastases to the cervical lymph nodes from a occult primary (CUP) of head and neck squamous carcinomas has been increasing in presentation (HNSCC). Modern diagnostic workup, including clinical evaluation, conventional imaging, FDG-PET/CT and panendoscopy/tonsillectomy enables detection of the primary site in over half of all cases, and is associated with significantly improved survival rates. Recent studies have demonstrated the utility of novel molecular pathology and transoral surgical techniques in improving diagnosis and treatment. We present a new, evidence-based protocol incorporating these novel diagnostic modalities. It aims to identify the site of the primary tumor, and determine the stage of the disease, including extranodal extension. This information can personalise treatment recommendations, rationalise combinations of treatment modalities, and thereby potentially minimise toxicity and improving functional outcomes.

https://ift.tt/2Q5BYGW

Grainyhead-like-2 confers NK-sensitivity through interactions with epigenetic modifiers

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Ian MacFawn, Hannah Wilson, Luke A. Selth, Ian Leighton, Ilya Serebriiskii, R. Christopher Bleackley, Osama Elzamzamy, Joshua Farris, Phillip M. Pifer, Jennifer Richer, Steven M. Frisch

Abstract

Natural Killer (NK) cells suppress tumor initiation and metastasis. Most carcinomas are heterogeneous mixtures of epithelial, mesenchymal and hybrid tumor cells, but the relationships of these phenotypes to NK susceptibility are understood incompletely. Grainyhead-like-2 (GRHL2) is a master programmer of the epithelial phenotype, that is obligatorily down-regulated during experimentally induced Epithelial-Mesenchymal Transition (EMT). Here, we utilize GRHL2 re-expression to discover unifying molecular mechanisms that link the epithelial phenotype with NK-sensitivity. GRHL2 enhanced the expression of ICAM-1, augmenting NK-target cell synaptogenesis and NK killing of target cells. The expression of multiple interferon response genes, including ICAM1, anti-correlated with EMT. We identified two novel GRHL2-interacting proteins, the histone methyltransferases KMT2C and KMT2D. Mesenchymal-epithelial transition, NK-sensitization and ICAM-1 expression were promoted by GRHL2-KMT2C/D interactions and by GRHL2 inhibition of p300, revealing novel and potentially targetable epigenetic mechanisms connecting the epithelial phenotype with target cell susceptibility to NK killing.

https://ift.tt/2zz0iGG

Hippo kinase NDR2 inhibits IL-17 signaling by promoting Smurf1-mediated MEKK2 ubiquitination and degradation

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Xianwei Ma, Dan Wang, Na Li, Peng Gao, Mei Zhang, Yan Zhang

Abstract

NDR/LATS kinase family are conserved from yeast to man and their roles in inflammation remains largely unknown. In the present study, we show that knockdown of NDR2 significantly increases IL-17-induced IL-6, CXCL2 and CCL20 expression in Hela and HT-29 cells. Knockdown of NDR2 enhances IL-17-induced MAPK and NF-κB activation. NDR2 interacts with E3 ubiquitin protein ligase Smurf1, promotes Smurf1-mediated K48-linked ubiquitination of MEKK2 and inhibits expression of MEKK2. Consistently, knockdown of Smurf1 increases IL-17-induced IL-6, CXCL2 and CCL20 expression. On the other hand, overexpression of MEKK2 increases IL-17-induced IL-6 expression. These results suggest that NDR2 may play important roles in IL-17-associated inflammation by promoting Smurf1-mediated MEKK2 ubiquitination and degradation.

https://ift.tt/2PdyRaj

Foreign bodies in the ear, nose, and throat in Japan: association with sociocultural and geographical conditions

Publication date: Available online 1 December 2018

Source: Auris Nasus Larynx

Author(s): Ryohei Oya, Arata Horii, Atsuhiko Uno, Yoshiaki Kawasaki, Hidenori Inohara

Abstract

Objective

Foreign bodies (FBs) in ear, nose, and throat (ENT) are common ENT emergencies but are sometimes life-threatening. However, FBs could be avoidable by the efficient announcement about the risk of these occurrence to the public. Fish bones are commonly found as throat FBs, and small toys are commonly found as pediatric ear and nose FBs. We hypothesized that there were relationships between the occurrence of FBs and sociocultural/geographical conditions. The purpose of this study is to clarify the risk factors of FBs in ENT regions related to eating customs and weather conditions.

Methods

From April 2009 to March 2014, 94,479 patients visited the Chuo Emergency Clinic (CEC) in Osaka, which is a local emergency center for Osaka prefecture in Japan. Among them, 3229 patients with throat FBs, 577 children (0–15 years of age) with ear FBs, and 1999 children (0–15 years of age) with nose FBs were enrolled into the present study. Monthly trends in the number of throat FBs were examined in relation to fish eating customs. The monthly average of the daily ratio of pediatric patients with ear or nose FBs to the total number of patients were examined in relation to weather parameters using a database of the Japan Meteorological Agency.

Results

The incidence of throat FBs was significantly higher in July and January (p < 0.05, analyzed by ANOVA and Tukey–Kramer test), presumably because Japanese people have more chances to eat fish in these months due to the traditional fish-eating customs. There was also a significant correlation between the number of pediatric patients with ear and nose FBs and the bad weather parameters including daily rainfall (r = 0.76, p = 0.0043; r = 0.57, p = 0.050, respectively, analyzed by the Pearson product-moment correlation coefficient). This is because children would spend longer time inside on rainy days, which increases the chance of putting a small toy part in the ear and nose.

Conclusions

FBs in throat and ear/nose occurred more frequently in the specific periods to eat fish and rainy days, respectively. Therefore, public announcement on the risk of occurrence of FBs based on sociocultural and geographical data is helpful to prevent FBs.

https://ift.tt/2RrlDZH

Levothyroxine Replacement Therapy and Overuse: A Timely Diagnostic Approach

Thyroid, Ahead of Print.


https://ift.tt/2KKU3Ec

Split-mouth evaluation of connective tissue graft with or without enamel matrix derivative for the treatment of isolated gingival recession defects in dogs

Abstract

Objectives

The potential additive effect of an enamel matrix derivative (EMD) to a subepithelial connective tissue graft (CTG) for recession coverage is still controversially discussed. Therefore, the aim of this study was to histologically evaluate the healing of gingival recessions treated with coronally advanced flap (CAF) and CTG with or without EMD in dogs.

Materials and methods

Gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 7 dogs. After 8 weeks of plaque accumulation and subsequent 2 weeks of chemical plaque control, the 14 chronic defects were randomized to receive either CAF with CTG (CAF/CTG) or CAF with CTG and EMD (CAF/CTG/EMD). The animals were sacrificed 10 weeks after reconstructive surgery for histologic evaluation.

Results

Treatment with CAF/CTG/EMD demonstrated statistically significantly better results in terms of probing pocket depth reduction (P < 0.05) and clinical attachment level gain (P < 0.001). The length of the epithelium was statistically significantly shorter in the CAF/CTG/EMD group than in the CAF/CTG group (1.00 ± 0.75 mm vs. 2.38 ± 1.48 mm, respectively, P < 0.01). Cementum formation was statistically significantly greater in the CAF/CTG/EMD group than following treatment with the CAF/CTG group (3.20 ± 0.89 mm vs. 1.88 ± 1.58 mm, respectively, P < 0.01). The CAF/CTG/EMD group showed statistically significantly greater complete periodontal regeneration (i.e., new cementum, new periodontal ligament, and new bone) than treatment with CAF/CTG (0.54 ± 0.73 mm vs. 0.07 ± 0.27 mm, respectively, P < 0.05).

Conclusion

Within their limits, the present findings indicate that the additional use of EMD in conjunction with CAF + CTG favors periodontal regeneration in gingival recession defects.

Clinical relevance

The present findings support the use of EMD combined with CTG and CAF for promoting periodontal regeneration in isolated gingival recession defects.

https://ift.tt/2E9eZV5

The South Asian Facial Anthropometric Profile: A Systematic Review

Craniofacial anatomy, as measured by facial anthropometric data, varies significantly between races. South Asia, comprised of eight countries, represents a large proportion of the global population and is the fastest-growing region of the world. This systematic review presents the facial anthropometric data collected for populations from this region.

https://ift.tt/2rbAk7C