Yu Si

Attenuated TLRs in middle ear mucosa contributes to susceptibility of chronic suppurative otitis media

The variability in the recovery of otitis media (OM) is not well understood. Recent data have shown a critical role for toll-like receptors (TLRs) in inflammatory responses to bacteria. It remains unclear whether TLRs-mediated mucosal immunity plays a role in the OM recovery. The etiology, pathological profile, expression levels of TLR2, TLR4, TLR5, TLR9 and proinflammatory cytokines were measured in human middle-ear mucosae sampled from three subject groups: non-OM group, chronic otitis-media (COM) group, and chronic suppurative otitis-media (CSOM) group. Of the 72 ears, 86.11% CSOM patients were positive for bacteria. The cellular makeup of the middle ear mucosa differs among the three groups. Mucosae from the CSOM group presented chronic inflammation or suppurative inflammation in the rudimentary stroma, mainly with infiltration of monocytes and macrophages. The mRNA and protein levels of TLR2, TLR4, and TLR5 exhibited no difference between the non-OM and COM groups but were significantly lower in the CSOM group. Conversely, there was no significant difference in the TLR9 level among the three groups. Furthermore, proinflammatory cytokines TNF-α, IL-1β, IFN-γ, IL-6 were up-regulated in the CSOM group. This study provides evidence that the variability in clinical otitis media recovery might be associated with the variability in the expression of mucosal TLRs. Reduced TLR levels in the middle-ear mucosa might cause weak host response to bacteria, persistent inflammation and susceptibility to CSOM.

Three autologous substitutes for myringoplasty: a comparative study.

Objective: Evaluation of 3 different kinds of autologous substitutes for simple myringoplasty. Study Design: Retrospective review of myringoplasty cases. Patients: A total of 117 patients (52 women with 52 ears and 65 men with 65 ears) with an average age of 25.6 years (range, 12-51 yr) were examined. Forty-two cases exhibited large perforations, and 75 exhibited small perforations. Intervention: Myringoplasty with temporal fascia, tragus perichondrium, or tragus cartilage-perichondrium composite grafts were randomly used in this comparative study. All the 117 operations were performed by a single surgeon. Main Outcome Measures: Otoscopic findings as assessed by a hearing examination using a quad-frequency pure-tone average air-bone gap. Results: Recurrent defects were not observed in the small perforation group repaired with autologous substitutes. The graft acceptance rate in this group was 100%. For the large perforation group, the graft acceptance rate was highest with the cartilage-perichondrium composite grafts group (p < 0.05) 1 year after the operation. Tympanic membranes repaired with temporalis fascia or perichondrium eventually perforated again or seemed invaginated and adherent. Early hearing improvements in the temporalis fascia and perichondrium groups were better than that of cartilage-perichondrium composite grafts, but there was no significant difference 1 year after surgery. Conclusion: Temporal fascia, tragus perichondrium, and tragus cartilage-perichondrium composite grafts are all suitable for myringoplasty after a minor tympanic membrane perforation. However, cartilage-perichondrium composite graft material for myringoplasty has superior long-term benefits in regard to both hearing improvements and tympanic membrane morphology, which are especially evident in cases with large perforations.

TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction.

Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1β. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction, and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1β expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis.

Hodgkin's lymphoma of the temporal bone accompanied by intracranial abscess.

The site with the greatest predilection for lymphoma in the head and neck is Waldeyer’s ring. The ocular adnexa, paranasal sinuses, salivary glands, oral cavity, larynx, thyroid gland, eye, and even the temporal bone are other sites within this region in which lymphoma may occur (1). Only 18 cases of primary temporal bone lymphoma were reported in the past 20 years (2). Most of these lymphomas are non-Hodgkin’s lymphoma (NHL), whereas cases of Hodgkin’s lymphoma (HL) are extremely rare (3,4). HL accounts for approximately 1% to 4% of lymphomas in extranodal diseases and is notably less common than NHL (25%Y30%) (5). Here, we report a case of HL that arose in the temporal bone, accompanied by an intracranial abscess; such a case has not been reported in the literature previously. A 49-year-old woman presented with a painful mass in the left mastoid region for 5 months. The patient described that the mass had expanded gradually, accompanied by left temporal bone tenderness, headache, and tinnitus in the left ear; however, she did not experience fever, hearing loss, vertigo, or vomiting. At that point, she went to the hospital for further examination. A temporal bone magnetic resonance imaging scan showed a rounded mass with mixed signals in the left temporal lobe that was later proven to be an epidural abscess (Fig. 1). A simple mastoidectomy on her left side had been performed 3 months previously; however, a relapse soon followed, and the incision remained unhealed (Fig. 2A). Temporal bone computed tomography revealed a lytic destructive lesion in the left temporal bone (Fig. 2B). Recently, a reoperation was attempted. During the operation, the mastoid pneumatic space was found to be filled with necrotic tissue. Although the intracranial structure was involved, and an epidural abscess formed, the tympanic cavity remained intact (Fig. 2C). A tissue sample from the mastoid cavity was collected for histopathologic examination. Histopathologic and immunohistochemical analysis showed a lymphocyte-predominant background and the presence ofCD30-positive lymphomatous cells (Fig. 3). The histopathologic diagnosis was lymphocyte-rich classic HL. Later, systemic chemotherapy was administered, and no recurrence has been observed to date. As classified by the World Health Organization (WHO), HL is subdivided into 2 main types: nodular lymphocyte predominant and classic HL. Classic HL includes the following subtypes: nodular sclerosis, lymphocyte-rich classic, mixed cellularity, lymphocyte-depleted, and unclassifiable classic HL. Its diagnosis is based on the identification of characteristic multinucleated giant cells within an inflammatory milieu. These cells, termed Reed-Sternberg (RS) cells, represent the body of the tumor. RS cells measure 20 to 60 Km in diameter and display a large rim of cytoplasm

Autologous Meatal Skin Graft Implantation and Intratympanic Injection of Pseudomonas aeruginosa: A New Experimental Mouse Model of Acquired Middle Ear Cholesteatoma

Aim: To create an experimental model for the biomedical research of middle ear cholesteatoma. Methods: Cholesteatoma was induced in the right ears of mice. An autologous meatal skin graft was implanted into the middle ear via the tympanic membrane followed by an intratympanic injection of Pseudomonas aeruginosa. Six weeks after surgery, the formation of acquired cholesteatoma was evaluated by macroscopic examination, CT scan, and histological analysis. The expressions of TNF-α, IL-1β, and IL-6 were measured with real-time PCR. Auditory-evoked brain stem response was used for assessing the changes in hearing levels. Results: None of the mice died during the modeling time. By the sixth postoperative week, cholesteatoma had successfully formed in 23 out of 25 mice, which equals a success rate of 92%. A CT scan revealed that the cholesteatoma was eroding the cochlea. Furthermore, histological analysis demonstrated a cystic structure covered by stratified squamous epithelium and keratin desquamation in the lamellae inside the cystic cavity in the bullae. All mice with experimentally induced cholesteatoma showed hearing impairment and an upregulated expression of TNF-α, IL-1β, and IL-6. Conclusion: The present study successfully developed a mouse model of acquired middle ear cholesteatoma, which provides an extremely valuable tool for auditory and biomedical research. The modeling approach is technically easy and has a high success rate.

TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation

Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1β and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation.

Osseointegration technique in patients with acquired auricular deformities and failed previous reconstruction: a retrospective study of long-term follow-up and Chinese experience.

Objectives: To evaluate the complication rate and patient satisfaction of reconstruction of acquired auricular deformities and failed previous reconstruction by the osseointegration technique. Methods: The study enrolled 24 patients from January 2002 to December 2005. Data collected included demographic information, success rate of auricular prostheses, site of implants, survival rate of implants, occurrence of skin reaction and condition of the prosthetic ear. Results: Twenty-five ears (24 patients) were implanted. All ears were healing well with a lifelike appearance, stable fixation and natural color; except for 2 instances of implants dislocated by trauma, the rest survived well by first intention; skin reaction was the most troublesome complication, no patient was able to maintain a consistent level of soft-tissue health for the whole follow-up period, but the ratio and degree of skin reaction decreased gradually. The time of wearing prosthetic ears was more than 8 h/day. The average time length until prosthetic ear replacement was 3.5 years. There were no intracranial or systemic complications. Conclusion: The osseointegration technique can be the method of choice for acquired auricular defects and failed reconstructions. Follow-up management is important to the health of the implants and the surrounding soft tissue and to preserve the prosthesis and its retention mechanism.

Effects of combination of balloon Eustachian tuboplasty with methylprednisolone irrigation on treatment of chronic otitis media with effusion in adults

PURPOSE Adult chronic otitis media with effusion (COME) is characterized by Eustachian tube dysfunction and mucosal inflammation, which management has long been a challenge because of high recurrence. This study was to investigate the pathological changes of Eustachian tube mucosa and optimized treatment. MATERIALS AND METHODS Retrospective study of four groups: I: tympanic paracentesis, II: balloon Eustachian tuboplasty (BET), III: BET plus tympanic paracentesis, IV: BET and tympanic paracentesis with methylprednisolone irrigation. Biopsy of Eustachian tube mucosa was obtained preoperative and 1 month post. Recurrence ratio and Eustachian tube scores (ETS) were used to evaluate the effect of treatments. RESULTS All patients showed narrowed with edematous and thickened Eustachian tube mucosa. At 1 month post-treatment, BET with methylprednisolone irrigation significantly decreased intraepithelial inflammation and restored the quality of epithelium and cilia. For group II to IV, The recurrence rate was significantly lower in group IV compared with the other two, but only significantly lower in group IV VS group II at 3 months and 6 months, no significant difference at 12 months. The recurrence rate was significantly higher in group I during follow-up. The ETS were improved in group II, III and IV after treatment. At 1 month and 3 months posttreatment, group IV had significant higher ETS compared with other groups (P < 0.05). There was no serious complications occurred. CONCLUSION Methylprednisolone irrigation could help to recover mucosal function. BET and tympanic paracentesis with methylprednisolone irrigation could be regarded as a good choice for COME in adults, which has less recurrence rate and prompt recovery of ET function.

Author’s reply to a letter-to-the-editor about the paper ‘Eardrum thickening approach for the treatment of patulous Eustachian tube’

Thank you for the invitation. We appreciate so many useful advises and arguments from the author of the letter. This study mainly discussed the approach of eardrum thickening for the treatment of patulous Eustachian tube (PET), as well as its possible mechanism. It proved to be a helpful method for the relief of the symptoms, which could be seen from the preliminary results. The author of the letter suggested that oto-endoscopic surgery might be more invasive, and we consider that could be a meaningful option. We agree that local managements of the Eustachian tube (ET) are indeed important for the therapy of this disease, which commonly focus on the pharyngeal orifice of the ET. Numerous attempts on surgical tubal closure have been described, in which outcome measures have varied significantly between individual studies, with overall symptom improvements reported between 22 and 100% (mean 72.4%) [1]. Literatures [2, 3] have shown that mucous-thickening via conjugated estrogen drops and Teflon/fat injection could reconstruct the tubal orifice, but its effectiveness was usually temporarily. Tube occlusion by means of plug, cauterizing and suture ligation may achieve lasting relief of symptoms. However, these manipulations may lead to effusion of the middle ear, generally requiring long-term ventilation tube insertion. Overall, the ideal management of the PET remains to be defined. The eardrum thickening approach that we reported had shown benefit to the relief of the three symptoms, according to the VAS changes. Possible mechanism might be that it restricted the gross outward movements of the acoustic transmission system that caused abnormal fluctuation of the perilymph, as referred in our previous report. Meanwhile, the ET mucosa can be protected from irreversible trauma, and left for the possible chance of a more desirable reconstruction skill in the future. So we believe this approach can be a sensible choice. As PET is a relative infrequent disease, literatures generally report a small study population that it is hard to draw significant conclusions. Although our exploration also included only a small number of patients, it demonstrated the effectiveness of our surgical procedure preliminarily. Thus, it is worthy to further increase the population size and the follow-up time, to better assess the efficacy of cartilage myringoplasty on the PET over time. Yu Si and Yubin Chen contributed equally to this work.

Measurements of the position relationship between the inferior margin of the oval window and the endosteum of basal cochlear turn in histologic and HRCT study.

Hypothesis To identify the optimum and safe location histologically for drilling and fenestration on promontory inferior to the oval window in stapedectomy. The value of application of high-resolution computed tomography (HRCT) scanning and multiple-planar reconstruction (MPR) for this purpose is also assessed. Methods By means of histologic sections and HRCT scanning and MPR for coronal image, measurements were conducted on 3 perpendicular planes in temporal bone sections through the anterior, posterior, and midpoint of the inferior margin of the oval window, respectively. Results The promontory bone inferior to the posterior portion of the oval window is thickest, which has an average thickness of about 1.1 mm. The endosteum of the basal turn here is deepest under the promontory, which has an average height of about 0.2 mm above the plane of footplate, whereas the distance between the inferior margin of the oval window and the endosteum here is no more than 0.3 mm. The coincidence rate of the measurements by HRCT and histology is up to 90.5%. Conclusion Relatively safe location for bone of the promontory removal should be restricted in the posterior portion inferior to the oval window, and the burr should be lifted laterally while drilling. Preoperative HRCT scanning and MPR for coronal image would offer a valuable reference to estimate the safe area for bone of the promontory removal in stapedectomy.