The Management of rNPC: Salvage Surgery vs. Re-irradiation.

PURPOSE OF REVIEW: Treatment failure, in the form of either persistence or local recurrence, occurs in 10 to 30% of nasopharyngeal carcinoma patients after initial radiotherapy (RT). Early detection of persistent or recurrent disease aids in the recognition of tumors that can be candidates for salvage nasophayngectomy or re-irradiation. There is no consensus till now on the indications or selection of the above two salvage treatment. RECENT FINDINGS: In recent years, there has been a paradigm shift from open to endoscopic approach for nasopharyngectomy, which carries nearly no complications. For salvage re-irradiation, intensity-modulated radiotherapy (IMRT) is the most commonly indicated modality. Compared to IMRT, salvage endoscopic nasopharyngectomy may be more beneficial in terms of prolonging survival, improving quality of life, and minimizing treatment-related complications and medical costs in a selected subset of recurrent nasopharyngeal carcinoma (rNPC) patients. Salvage nasopharyngectomy should be the mainstay of treatment for rNPC.

Peptidoglycan induces bradykinin receptor 1 expression through Toll-like receptor 2 and NF-κB signaling pathway in human nasal mucosa-derived fibroblasts of chronic rhinosinusitis patients.

Numerous studies have demonstrated that Gram-positive microbiomes play an important role in the pathogenesis and in the way of treatment of chronic rhinosinusitis (CRS). Kinins are inflammatory mediators and one of their receptors, namely bradykinin receptor 1 (BKR1 or B1R), is believed to be induced and involved in inflammation in pathophysiological conditions. In the present study, we investigated the effect of peptidoglycan (PGN), a major cell wall component of G(+) bacteria, on BKR expression and its signaling pathway in nasal fibroblasts from CRS without nasal polyp (CRSsNP). The PGN induced increases in B1R mRNA and protein production. The induction was abolished by the NF-κB and protein kinase A inhibitor. In parallel, the PGN treatment directly activated IκB/NF-κB signaling and CREB phosphorylation. Interestingly, a further analysis suggested no involvement of cAMP/PKA/CREB pathway in this induction. The B1R expression and IκB/NF-κB signaling pathway could be attenuated by Toll-like receptor-2 (TLR2) blocking/neutralizing Ab. In a functional assay, the addition of B1R selective agonist (Des-Arg10 -kallidin) to the fibroblasts after PGN stimulation led to an increase in CXCL8 release and p38 MAPK and ERK1/2 phosphorylation, which could be inhibited by the B1R antagonist. Taken together, our results revealed for the first time that PGN can increase B1R expression in human nasal mucosa-derived fibroblasts through TLR2 activation and NF-κB signaling pathway. This induction functionally leads to MAPKs activation and CXCL8 release upon B1R stimulation. Our results also suggest that a major component of G(+) bacteria can participate in B1R upregulation in nasal mucosa during CRSsNP progression.

Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps.

Numerous studies have shown that microbiomes play an important role in the pathogenesis of chronic rhinosinusitis (CRS). In addition to a known short pentraxin, C-reactive protein, long pentraxin 3 (PTX3) belongs to pentraxin family which detects conserved microbial pentraxin motifs and mobilizes early defense against foreign invaders, but its participation in CRS remains unclear. In the present study, through an intensive screening, peptidoglycan (PGN) was selected as a main material to investigate the action mechanism of a cell wall component on CRS without nasal polyps (CRSsNP) nasal mucosa-derived fibroblasts and the PTX3 expression in human nasal mucosa tissue and discharge. The PGN not only enhanced PTX3 mRNA and protein production in cells but also caused marked PTX3 secretion into extracellular space. The pharmacological interventions indicated that the PTX3 induction was mediated mainly through toll-like receptor 2 (TLR2), phosphoinositide-phospholipase C (PI-PLC), protein kinase C (PKC), NF-κB, and cAMP response element binding protein (CREB), which was further confirmed by the observations that a direct PKC activator (phorbol ester) had a similar inductory effect on PTX3 expression/production and the siRNA interference knockdown of PKCµ/δ, NF-κB, and CREB compromised PTX3 production. Meanwhile, PTX3 was found to be overexpressed/produced in nasal mucosa and discharge/secretion of the CRSsNP patients. Collectively, we first demonstrated here that PGN enhances PTX3 expression and release in nasal fibroblasts through TLR2, PI-PLC, PKCµ/δ, NF-κB, and CREB signaling pathways. The PTX3 is overexpressed in nasal mucosa and discharge/secretion of CRSsNP patients, revealing its possible importance in CRSsNP development and progression. KEY MESSAGES: Long pentraxin 3 (PTX3) is highly expressed in nasal mucosa and discharge/secretion of patients of chronic rhinosinusitis without nasal polyps (CRSsNP). The bacteria cell wall component-peptidoglycan (PGN) causes PTX3 expression in CRSsNP nasal mucosa-derived fibroblasts, contributing to the PTX3 increase in tissues. PGN induces PTX3 expression through a previously known IκB/NF-κB and a novel PKCµ/δ and CREB signaling pathway. The PTX3 may be used as a biomarker for CRS.

A New Trend in the Management of Esophageal Foreign Body: Transnasal Esophagoscopy.

OBJECTIVES: (1) To analyze the outcomes of patients with esophageal foreign body managed by transnasal esophagoscopy. (2) To review the value of lateral neck X-ray. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. SUBJECTS AND METHODS: Lateral neck X-ray was used for initial screening in patients suspected of having an esophageal foreign body between 2007 and 2013. Rigid esophagoscopy was used as standard for further investigations before July 2010 and transnasal esophagoscopy after July 2010. RESULTS: From January 2007 to June 2010, 43 patients who were suspected of having an esophageal foreign body under lateral neck X-ray received rigid esophagoscopy, 31 of whom were found to have an esophageal foreign body. From July 2010 to December 2013, 302 patients underwent transnasal esophagoscopy, and an esophageal foreign body was noted in only 52 of these patients. In the 302 patients who underwent transnasal esophagoscopy, the sensitivity and specificity of having an esophageal foreign body by lateral neck X-ray were 59% and 83%, respectively. CONCLUSION: The introduction of transnasal esophagoscopy has changed the diagnosis and management for an esophageal foreign body. Transnasal esophagoscopy is a quick and safe procedure that can be performed under local anesthesia. Transnasal esophagoscopy could replace lateral neck X-ray to become the initial screening procedure and a useful treatment for patients with an esophageal foreign body.