Endoscopic surgery versus intensity-modulated radiotherapy in locally advanced recurrent nasopharyngeal carcinoma: a multicenter, case-matched comparison.

BACKGROUND: The management of locally advanced recurrent nasopharyngeal carcinoma (rNPC) is challenging. The objective of our study was to compare salvage endoscopic nasopharyngectomy (ENPG) with intensity-modulated radiotherapy (IMRT) in clinical outcomes and complications of locally advanced rNPC. METHODS: Patients with histologically confirmed rNPC in rT3-4N0-3M0 stages were retrospectively enrolled between January 2013 and December 2019 in this multicenter, case-matched study. The baseline clinicopathological characteristics of patients were balanced by propensity score matching between the ENPG and IMRT groups. ENPG was performed in patients with easily or potentially resectable tumors. The oncological outcomes as well as treatment-related complications were compared between two groups. RESULTS: A total of 176 patients were enrolled and 106 patients were matched. The ENPG group (n = 53) and the IMRT group (n = 53) showed comparable outcomes in the 3-year overall survival rate (68.4% vs. 65.4%, P = 0.401), cancer-specific survival rate (80.9% vs. 74.4%, P = 0.076), locoregional failure-free survival rate (36.6% vs. 45.3%, P = 0.076), and progression-free survival rate (27.5% vs. 32.3%, P = 0.216). The incidence of severe treatment-related complications of patients in the ENPG group was lower than that in the IMRT group (37.7% vs. 67.9%, P = 0.002). The most common complications were post perioperative hemorrhage (13.2%) in ENPG group and temporal lobe necrosis (47.2%) in IMRT group, respectively. CONCLUSION: Salvage ENPG exhibits comparable efficacy but less toxicities than IMRT in carefully screened patients with locally advanced rNPC, which may be a new choice of local treatment.

Vascular endothelial growth factor is required for regeneration of auditory hair cells in the avian inner ear.

Hair cells in the auditory organ of the vertebrate inner ear are the sensory receptors that convert acoustic stimuli into electrical signals that are conveyed along the auditory nerve to the brainstem. Hair cells are highly susceptible to ototoxic drugs, infection, and acoustic trauma, which can cause cellular degeneration. In mammals, hair cells that are lost after damage are not replaced, leading to permanent hearing impairments. By contrast, supporting cells in birds and other non-mammalian vertebrates regenerate hair cells after damage, which restores hearing function. The cellular mechanisms that regulate hair cell regeneration are not well understood. We investigated the role of vascular endothelial growth factor (VEGF) during regeneration of auditory hair cells in chickens after ototoxic injury. Using RNA-Seq, immunolabeling, and in situ hybridization, we found that VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 were expressed in the auditory epithelium, with VEGFA expressed in hair cells and VEGFR1 and VEGFR2 expressed in supporting cells. Using organotypic cultures of the chicken cochlear duct, we found that blocking VEGF receptor activity during hair cell injury reduced supporting cell proliferation as well as the numbers of regenerated hair cells. By contrast, addition of recombinant human VEGFA to organ cultures caused an increase in both supporting cell division and hair cell regeneration. VEGF's effects on supporting cells were preserved in isolated supporting cell cultures, indicating that VEGF can act directly upon supporting cells. These observations demonstrate a heretofore uncharacterized function for VEGF signaling as a critical positive regulator of hair cell regeneration in the avian inner ear.

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium.

Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics. In mature basilar papillae, BMP4 mRNA is highly expressed in hair cells, but not in hair cell progenitors (supporting cells). Supporting cells transcribe genes encoding receptors for BMP4 (BMPR1A, BMPR1B, and BMPR2) and effectors of BMP4 signaling (ID transcription factors). Following hair cell destruction, BMP4 transcripts are lost from the sensory epithelium. Using organotypic cultures, we demonstrate that treatments with BMP4 during hair cell destruction prevent supporting cells from upregulating expression of the pro-hair cell transcription factor ATOH1, entering the cell cycle, and fully transdifferentiating into hair cells, but they do not induce cell death. By contrast, noggin, a BMP4 inhibitor, increases numbers of regenerated hair cells. These findings demonstrate that BMP4 antagonizes hair cell regeneration in the chicken basilar papilla, at least in part by preventing accumulation of ATOH1 in hair cell precursors.

Preparation and performance of a pH-sensitive cisplatin-loaded magnetic nanomedicine that targets tumor cells via folate receptor mediation.

The present study aimed to prepare cisplatin (CDDP)-loaded magnetic nanoparticles (MNPs), which target folate receptors via a pH-sensitive release system (FA­PEG­NH­N=MNPs­CDDP). This is of interest for the development of intelligent drug delivery systems that target tumors of the head and neck. The chemical coprecipitation method was used to prepare ferroferric oxide MNPs. These were modified with aldehyde sodium alginate complexed with the chemotherapeutic agent, CDDP on the surface of the nanoparticles. Double hydrazine­poly(ethylene glycol; PEG) was also prepared by attaching the carboxyl group of hydrazine­folate on one side of the double hydrazine­PEG, obtaining folate­hydrazine­PEG­diazenyl. This binds the aldehyde group of sodium alginic acid on the MNP to enclose CDDP, in order that it is sequestered within the carrier. This method obtained a pH­sensitive, FA­modified CDDP­loaded MNP (FA­PEG­NH­N=MNPs­CDDP), which acts as an intelligent tumor targeting drug delivery system. The mean size of the MNPs was ~10.2±1.5 nm, the mean hydrodynamic diameter detected by laser particle sizing instruments was 176.6±1.1 nm, and the ζ­potential was ­20.91±1.76 mV. The CDDP content was 0.773 mg/ml, the iron content was ~1.908 mg/ml and the maximum saturation magnetization was 16.3±0.2 emu/g. The current study produced a pH­sensitive FA­modified CDDP­loaded MNP that is stable and exhibits magnetic responsiveness, which releases CDDP in a low pH environment.

[Effect of piperphentonamine hydrochloride on expressions of interleukin-1ß and TNF-α mRNA and Fas protein in guinea pigs with cochlear ischemia/reperfusion injury].

OBJECTIVE: To investigate the relationship between IL-1ß and TNF-α mRNA and Fas protein expressions and cochlear ischemia reperfusion injury and investigate the protective mechanism of PPTA against cochlear reperfusion injury. METHODS: Sixty-four guinea pigs were randomly divided into normal control group, blank control group, ischemia/reperfusion (by clamping the bilateral vertebral artery and right common carotid artery for 1 h) control group, and ischemia/reperfusion with PPTA treatment group. In PPTA group, PPTA was injected via the femoral vein immediately after reperfusion, and ischemia/reperfusion control group received saline injection. In 6 guinea pigs from each group, the cochlear tissues were removed after 24 h of reperfusion for examination of expressions of IL-1ß and TNF-α mRNA by real-time PCR, and the rest animals were used for immunohistochemical detection of Fas protein. RESULTS: Compared with those of normal group and blank control group, the expressions of IL-1ß and TNF-ß mRNA increased significantly after cochlear ischemia/reperfusion (P<0.001), but were lowered significantly by PPTA (P<0.001). Positive expression of Fas protein expression was detected in the Corti organ, spiral ganglion and stria vascularis in ischemia/reperfusion control group with significantly higher IOD values than those of the other 3 groups (P<0.05). The IOD value showed no significant difference between PPTA-treated group, normal control group, and blank control group (P>0.05). CONCLUSIONS: PPTA can suppress the expression of Fas protein and IL-1ß and TNF-ß mRNAs in the cochlea of guinea pigs with cochlear ischemia/reperfusion. The protective effect of PPTA against cochlear ischemia/reperfusion is mediated probably by inhibition of inflammatory responses and cell apoptosis.

[The impact of malleus processing in ossicular chain reconstruction on the therapeutic effect in patients with tympanosclerosis].

OBJECTIVE: To investigate the effect of different malleus treatments on the postoperative efficacy in the tympanosclerosis patients receiving ossicular chain reconstruction. METHOD: Fifty-nine patients (62 ears) with tympanosclerosis were treated by ossicular chain reconstruction. All the patients were divided into three groups, including malleus removal group (A, 24 ears), retaining only the malleus handle group (B, 18 ears) and the intact malleus group (C, 20 ears). All the patients were followed up 3 months pre-operation, 3 months and 1 year post-operation by audiometric measurement (the average hearing threshold at 0.5, 1.0, 2.0 kHz HI). Tympanic membrane was examined by ear endoscope. RESULT: The pre-operation mean air bone gap (ABG) in these groups were 40.07 +/- 77.56 dB, 37.31 +/- 76.45 dB, and 36.75 +/- 76.72 dB, among which the difference had no statistical significance (P > 0.05). At 3 months after operation, the ABG in all cases was improved at 0.5, 1 and 2 kHz. The difference of ABG improvement among these three groups had no statistical significance (P > 0.05). One year after surgery, the ABG of the three groups were decreased by 17.92 +/- 9.28 dB, 16.76 +/- 5.19 dB and 10.58 +/- 7.38 dB respectively. The hearing improvement in group C is less than the other two groups (P = 0.03, P = 0.016). The difference of hearing improvement between group A and group B had no statistical significance(P > 0.05). Group A and group B each have one case of tympanic membrane perforation and artificial ossicle falling off. CONCLUSION: The operating processes of malleus in ossicular chain reconstruction of patients with tympanosclerosis were introduced. In terms of short-term efficacy, the three groups showed no significant difference. However, the long-term efficacy of the patients in the group A and group B were better compared with the group C.

[Development of a hydrophilic anti-fogging agent for nasal endoscopy].

OBJECTIVE: To develop a transparent, non-toxic, non-irritating anti-fogging agent with long-lasting effect for nasal endoscopy. METHODS: The anti-fogging agent was prepared by mixing ethanol, propylene glycol, polyoxyethylene lauryl ether, sodium dodecyl sulfate, polyethylene glycol 400 and deionized water at different proportions based on an orthogonal test design. Twenty-seven test samples of the anti-fogging agents were obtained, which were colorless, transparent, and non-irritating, with a pH value of 7-8. Storz00 nasal endoscopy and its imaging system were used to test the anti-fogging time of the 27 samples, and each agent was tested for 3 times with medical Seoul iodine and 95% ethanol as control. RESULTS: The optimal composition of the anti-fogging agent was 20% ethanol, 10% propylene glycol, 20% polyoxyethylene lauryl ether, 4% sodium dodecyl sulfate, 4% polyethylene glycol, 42% deionized water. The anti-fogging time of this agent reached 15 min, significantly longer than that of medical Seoul iodine (4 min) and 95% ethanol (18 s). CONCLUSION: This anti-fogging agent for nasal endoscopes is colorless and safe and has a long anti-fogging time by forming a homogenous transparent membrane over the endoscopic lens.

[Cochlear implantation in patients with Waardenburg syndrome type II].

OBJECTIVE: To describe the multi-channel cochlear implantation in patients with Waardenburg syndrome including surgeries, pre and postoperative hearing assessments as well as outcomes of speech recognition. METHOD: Multi-channel cochlear implantation surgeries have been performed in 12 cases with Waardenburg syndrome type II in our department from 2000 to 2008. All the patients received multi-channel cochlear implantation through transmastoid facial recess approach. The postoperative outcomes of 12 cases were compared with 12 cases with no inner ear malformation as a control group. RESULT: The electrodes were totally inserted into the cochlear successfully, there was no facial paralysis and cerebrospinal fluid leakage occurred after operation. The hearing threshold in this series were similar to that of the normal cochlear implantation. After more than half a year of speech rehabilitation, the abilities of speech discrimination and spoken language of all the patients were improved compared with that of preoperation. CONCLUSION: Multi-channel cochlear implantation could be performed in the cases with Waardenburg syndrome, preoperative hearing and images assessments should be done.

[Experience of 76 cases of large vestibular aqueduct syndrome, clinical diagnosis and treatment].

OBJECTIVE: To explore the disease incidence, clinical symptoms, prevention and treatment measures of the large vestibular aqueduct syndrome (LVAS). METHOD: Retrospective analyse the medical history, hearing, vestibular function examination and treatment of 76 LVAS patients who were diagnosed in our department of Otolaryngology from 2002 to 2008. RESULT: Most patients (93.4%) showed sensorineural hearing loss. Part of patients (61.8%) showed air-bone conduction gap in low frequency. The hearing loss of 43 ears is > 40-60 dB HL, > 60 -80 dB HL 47 ears, > 80 dB HL 62 ears. Decline curve is the characteristic of the Audiogram. The decline in high-frequency 112 ears, flat curve in 29 ears, island hearing in 11 ears. Forty-six patients were conducted the vestibular function examination, which showed low vestibular function. Tympanogram showed that 141 ears are type A, 11 ears are type C. High-resolution CT scan revealed that vestibular aqueduct minimum diameter is 2.2 mm and the largest is 6.2 mm, with a wide opening and deep narrower, and showed the "triangle" or "flared". Forty-two cases of this group were simple dilatation of the vestibular aqueduct, and no large vestibular semicircular canal malformation or cochlear malformation. There was no intellectual and other development disorders. In accordance with the degree of hearing loss, 20 cases of patients restored hearing after drug treatment. Eleven were cases fit a suitable hearing aid and carried out the language rehabilitation training. Forty-five very severe patients were implanted the cochlear and mapping one month later. CONCLUSION: Fluctuative and progressive hearing loss is the main clinical symptoms of large vestibular aqueduct syndrome. The patients should be examined by high resolution CT scan of the temporal bone. There is no precise and effective treatment for the disease. It is very important for the deaf children who have residual hearing to fit hearing aids and carry out the language rehabilitation training as soon as possible. As for the patients who suffer from hearing loss severely and the hearing aid cannot achieve effective compensation, the cochlear implant should be considered.

[Cochlear implant in patients with congenital malformation of the inner ear].

OBJECTIVE: To summarize the clinical experience with multi-channel cochlear implantation in patients with inner ear malformations and evaluate and the outcomes of speech rehabilitation. METHODS: A retrospective study was conducted in 295 patients receiving cochlear implantation from 1998 to 2007, including 25 patients with large vestibular aqueduct syndrome (LVAS), 9 with Modini malformation, and 5 with common cavity deformity. All the patients received the Nucleus24 cochlear implants. In LVAS cases, 4 had Nucleus 24R (ST) implants, 8 had Contuor implants, 10 had Contuor Advance, and the remaining cases used Nucleus24(M) straight-electrode implants. RESULTS: Severe gusher appeared in 3 cases of LVAS, and perilymph fluctuation were seen in other 15 cases. Four patients with Mondini malformation and 2 with common cavity malformation also experienced severe gusher, but the electrodes were inserted smoothly in all the patients without postoperative facial paralysis or cerebrospinal fluid leakage. The hearing threshold in these patients was similar to that in patients with normal cochlear structure. After speech rehabilitation for over 6 months, the abilities of speech discrimination and spoken language improved in all the cases in comparison with the preoperative lingual functions. CONCLUSION: Multi-channel cochlear implantation can be performed in patients with inner ear malformation, but should not be attempted in patients with poor cochlear and cochlear nerve development. A comprehensive pre-operative radiographic and audiological evaluation is essential.

[Cochlear implantation in patients with large vestibular aqueduct syndrome].

OBJECTIVE: To evaluate the hearing and speech recognition in patients with large vestibular aqueduct syndrome undergoing multi-channel cochlear implantation. METHODS: From 2005 to 2008, multi-channel cochlear implantation surgeries were performed in 22 patients with large vestibular aqueduct syndrome. All the patients received multi-channel cochlear implantation through transmastoid facial recess approach. The postoperative outcomes of the patients were compared with those of 22 patients with non-malformed cochlear. RESULTS: Severe gusher occurred in 3 cases during the implantation, and perilymph fluctuation was found in another 15 cases, with a rate of anomalies of 81.8%. All the electrodes were totally inserted into the cochlear, and no facial paralysis or cerebrospinal fluid leakage occurred after the operation. The hearing threshold in these patients was similar to that in patients with normal cochlear receiving the implantation. After speech rehabilitation for over 6 months, all the patients showed improved hearing and verbal ability. CONCLUSION: Multi-channel cochlear implantation can be performed in patients with large vestibular aqueduct syndrome, but preoperative hearing assessment and radiographic examinations should be performed.

[Effect of surgical reconstruction of congenital aural atresia via the mastoid antrum approach: analysis of 48 cases].

OBJECTIVE: To assess the effect of surgical reconstruction of congenital aural atresia via the mastoid antrum approach and investigate method for preventing postoperative atresia of the reconstructed aural canal. METHODS: From 2000 to 2008, aural canal reconstruction and tympanoplasty was performed via the mastoid antrum approach. In 48 patients with congenital aural atresia (54 ears, including 45 ears of type II, 9 ears of type III). All the patients were followed-up for 18 months to assess the therapeutic effect. RESULTS: The mastoid antrum was located uneventfully for all the 54 ears, all showing ossicular chain anomalies involving most frequently the malleus and the incus followed by the upper structures of the stapes. Facial nerve abnormalities were seen in 23 ears (42.6%). Hearing improvement to over 20 dB was achieved in 45 ears (83.3%) and to over 25 dB in 25 ears (46.2%) one year later. CONCLUSION: The mastoid antrum approach for surgical reconstruction of congenital aural atresia is safe and reliable. Maintenance of the width of the aural canal and prevention of lateral healing of the transplanted tympanic membrane are crucial in the treatment of congenital aural atresia.

[Audiological assessment in 88 patients with otosclerosis].

OBJECTIVE: To analyze the clinical data of the hearing in otosclerosis patients and explore their association with the clinical manifestations. METHOD: A retrospective analysis of 88 otosclerosis cases (162 ears) was performed. Pure tone audiometry was performed in all the cases 1 to 3 days before the operation for speech analysis at the frequencies of 500, 1 k, 2 kHz and to determined the average pure-tone hearing threshold (PTA) and gas Bone gap (ABG). The incidence of carhart notch was observed in patients with simple conductive hearing loss and mixed hearing loss, and in the early, middle and late stage of otosclerosis. RESULTS: Carhart notch occurred at significant higher incidence in patients with simple conductive hearing loss and in early otosclerosis (P<0.05). CONCLUSION: For common otosclerosis, the lesion invades initially the vestibular window, round ligament and stapes floor, followed by the base of the cochlea, and therefore observation of the carhart notch may help determine the disease course.

[Therapeutic effects of small fenestra stapedotomy with semiconductor diode laser: a comparison with microdrill].

OBJECTIVE: To compare the effects of small fenestra stapedotomy with semiconductor diode laser and microdrill in patients with otosclerosis. METHODS: Twenty-six patients (29 ears) undergoing stapedotomy with semiconductor diode laser and 19 patients (21 ears) with microdrill were compared for the hearing results and complication rates. RESULTS: No statistically significant differences were found in postoperative speech frequency and high frequency pure tone average in closing the air-bone gap between the two groups. The ears treated by stapedotomy with semiconductor diode laser showed significantly better preoperative minus the postoperative air-bone gap and milder dizziness. CONCLUSION: In spite of the good hearing outcomes in both groups, small fenestra stapedotomy with semiconductor diodelaser can achieve better results and reduce the incidence of complications.

[Establishment of tympanosclerosis by intratympanic injection of Staphylococcus aureus in guinea pigs].

OBJECTIVE: To establish a guinea pig model of tympanosclerosis and investigate the development and progression of tympanosclerosis in the tympanic membranes and middle ear mucosa. METHODS: Twenty-one healthy guinea pigs were subjected inoculation of 1x10(8)/L Staphylococcus aureus into the left middle ear cavities under general anaesthesia, with the right ears as the control, to establish models of chronic purulent otitis media. The animals were sacrificed by decapitation after 1, 3 and 6 months after model establishment for histological examination of the middle ear mucosa. RESULTS: The histological changes of tympanosclerosis occurred in some of the animals 3 months after model establishment, and the extent of calcium deposition and fibrosis across the mucosa were positively correlated with the duration of chronic purulent otitis media. CONCLUSION: Tympanosclerosis may occur in some guinea pigs after inoculation of Staphylococcus aureus into the middle ear cavity, and this model can be useful for study of tympanosclerosis.

[Audiological assessment in 79 patients with tympanosclerosis].

OBJECTIVE: To conduct audiological assessment in patients with tympanosclerosis. METHODS: A retrospective review was conducted in 79 patients with tympanosclerosis (involving 79 ears) with complete records, including 30 patients (30 ears) with fixed Malleus-incus complex, 29 (29 ears) with fixed stapes, and 20 (20 ears) with fixations of both the stapes footplate and the Malleus-incus complex. Audiometry was performed for all the patients one or two days before operation, and the audiological features of the patients were compared between the 3 groups. RESULTS: Most of the patients (65.8%) suffered conductive hearing loss, 32.9% had mixed deafness, and one patient had sensorineural hearing loss. No statistically significant differences was noted in the speech frequency (0.5, 1, and 2 kHz) air conduction pure tone average (PTA) or the air-bone gap (ABG) in the 3 groups (P<0.05). CONCLUSION: Most of the patients with tympanosclerosis suffer conductive hearing loss, and the severity of hearing loss is not associated with the site of tympanosclerosis.

[Effects of ossicular reconstruction with partial ossicular replacement prosthesis in patients with tympanosclerosis].

OBJECTIVE: To evaluate the effect of ossicular reconstruction with partial ossicular replacement prosthesis (PORP) in patients with tympanosclerosis. METHODS: The data of 28 cases of tympanosclerosis treated between 1992 and 2006 were reviewed. Of the 28 patients, 14 (14 ears) underwent ossicular reconstruction with PORP and 14 (14 ears) had ossicular mobilization, and all the patients were followed-up for 3-24 months. RESULTS: Significant improvement was found in postoperative speech frequency (500, 1000, 2000 Hz) pure tone average (PTA) and air-bone gap (ABG) closure after in the operation the two groups. Ossicular reconstruction using PORP resulted in statistically better ABG closure and PTA (P<0.05). CONCLUSION: In ossicular attic fixation, ossicular reconstruction using PORP can yield better results than mobilization of the major ossicles in patients with tympanosclerosis.