Combination photobiomodulation/N-acetyl-L-cysteine treatment appears to mitigate hair cell loss associated with noise-induced hearing loss in rats.

Sensorineural hearing loss is an intractable disease. Acoustic overstimulation creates hearing loss; many patients exhibit social and emotional dysfunctions. In a model of noise-induced hearing loss (NIHL), low-level laser photobiomodulation (PBM) at a near-infrared wavelength significantly improved auditory brainstem response (ABR) thresholds. In addition, both N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) attenuated NIHL, reducing the effects of noise trauma in the cochlea and the central auditory system. Here, we combined PBM with antioxidants to explore hearing threshold recovery and morphological hair cell changes after rats were exposed to noise. The average auditory brainstem response thresholds after PBM/NAC combination treatment were reduced from the apex to the basal turn at all of 8, 16, and 32 kHz compared to the noise-only group. The PBM/NAC combination treated group exhibited intact outer hair cells in all turns, and significantly greater hair cell numbers in the middle and basal cochlear turns, than did controls. Thus, PBM/NAC treatment may prevent hearing dysfunction caused by NIHL.

Safety assessment of trans-tympanic photobiomodulation.

We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm(2). The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.

Effect of low-level laser therapy on cochlear hair cell recovery after gentamicin-induced ototoxicity.

Cochlear hair cells are the sensory receptors of the auditory system. It is well established that antibiotic drugs such as gentamicin can damage hair cells and cause hearing loss. Rescuing hair cells after ototoxic injury is an important issue in hearing recovery. Although many studies have indicated a positive effect of low-level laser therapy (LLLT) on neural cell survival, there has been no study on the effects of LLLT on cochlear hair cells. Therefore, the aim of this study was to elucidate the effects of LLLT on hair cell survival following gentamicin exposure in organotypic cultures of the cochlea of rats. The cochlea cultures were then divided into a control group (n = 8), a laser-only group (n = 8), a gentamicin-only group (n = 8) and a gentamicin plus laser group (n = 7). The control cultures were allowed to grow continuously for 11 days. The laser-only cultures were irradiated with a laser with a wavelength of 810 nm at 8 mW/cm(2) for 60 min per day (0.48 J/cm(2)) for 6 days. The gentamicin groups were exposed to 1 mM gentamicin for 48 h and allowed to recover (gentamicin-only group) or allowed to recover with daily irradiation (gentamicin plus laser group). The hair cells in all groups were stained with FM1-43 and counted every 3 days. The number of hair cells was significantly larger in the gentamicin plus laser group than in the gentamicin-only group. The number of hair cells was larger in the laser-only group than in the control group, but the difference did not reach statistical significance. These results suggest that LLLT may promote hair cell survival following gentamicin damage in the cochlea. This is the first study in the literature that has demonstrated the beneficial effect of LLLT on the recovery of cochlear hair cells.

Effect of vestibular rehabilitation on dizziness in the elderly.

OBJECTIVES: Dizziness in the elderly is relatively common, but only a few studies are available. The purpose of this study was to analyze the effect of vestibular rehabilitation on dizziness in elderly patients. MATERIALS AND METHODS: A total of 240 patients older than 70 years with dizziness who visited the dizziness center of a tertiary care university hospital from January 2000 to January 2004 were studied. The patients' charts were retrospectively reviewed. Thorough otolaryngologic and neurotologic evaluations and vestibular function testing were performed in every case to determine the specific causes of dizziness. General vestibular rehabilitation therapy (VRT) was performed in 103 cases (VRT group) and it was not done on the other 46 cases (non-VRT group). The intensity of dizziness and disequilibrium was evaluated by the verbal analogue scale and Activities-specific Balance Confidence questionnaires that were obtained at 3 weeks and at 3 months after the initiation of general VRT. RESULTS: The average age of the patients was 76.5 +/- 6.2 years. In 153 cases (63%), no specific causes for dizziness were found, which was attributed to presbyastasis. Improvement in dizziness in the VRT group was significantly higher than in the non-VRT group by the verbal analogue scale and Activities-specific Balance Confidence scale obtained at 3 weeks and at 3 months after the initiation of VRT. CONCLUSION: In the majority of elderly patients with dizziness, the etiology of dizziness is not found and is attributed to presbyastasis. General VRT seems to be an effective treatment for this elderly group.

Enhanced mitochondrial membrane potential and ATP synthesis by photobiomodulation increases viability of the auditory cell line after gentamicin-induced intrinsic apoptosis.

Photobiomodulation (PBM) has been suggested to have a therapeutic effect on irreversible hearing loss induced by aminoglycosides, including gentamicin (GM). However, its intracellular mechanism(s) in GM-induced ototoxicity remain poorly understood. In the present study, we investigated the effect of PBM in GM-induced ototoxicity in auditory cells. We tried to characterize the downstream process by PBM, and the process that triggered the increased cell viability of auditory cells. As a result, the effects of PBM against GM-induced ototoxicity by increasing ATP levels and mitochondrial membrane potential was confirmed. These results suggest a theory to explain the therapeutic effects and support the use of PBM for aminoglycoside-induced hearing loss.

Effect of Topical Propolis on Wound Healing Process After Tonsillectomy: Randomized Controlled Study.

OBJECTIVES: The post-tonsillectomy pain and post-tonsillectomy hemorrhage are the two main problems after tonsillectomy. The aim of this study was to investigate the beneficial effects of water soluble ethanol extract propolis on post-tonsillectomy patient. METHODS: One hundred and thirty patients who underwent tonsillectomy or adenotonsillectomy were randomly divided into the control and propolis groups, each including 65 patients. The propolis group was applied with propolis orally immediately after surgery and by gargle. The pain scores were assessed on post-tonsillectomy 0, 1st, 2nd, 3rd, and 7th-10th day using a visual analogue scale score. Postoperative wound healing was evaluated by scoring pinkish membrane of tonsillar fossae on postoperative days 3 and 7-10. The incidence of post-tonsillectomy bleeding was examined in each group. RESULTS: Post-tonsillectomy pain was significantly less in propolis group compared to control group on postoperative days 3 and 7-10. Post-tonsillectomy hemorrhage was significantly less in the propolis group compared to the control group (P<0.05). The wound healing was significantly better in the propolis group compared to the control group on postoperative day 7-10 (P=0.002). CONCLUSION: Applying the propolis to post-tonsillectomy wound showed beneficial effect of reducing postoperative pain, preventing hemorrhage, and accelerating of wound healing of tonsillar fossae.

Treatment of peripheral vestibular dysfunction using photobiomodulation.

Gentamicin, which is still used in modern medicine, is a known vestibular toxic agent, and various degrees of balance problems have been observed after exposure to this pharmacologic agent. Photobiomodulation is a candidate therapy for vertigo due to its ability to reach deep inner ear organs such as the cochlea. Previous reports have suggested that photobiomodulation can improve hearing and cochlea function. However, few studies have examined the effect of photobiomodulation on balance dysfunction. We used a rat model to mimic human vestibulopathy resulting from gentamicin treatment and evaluated the effect of photobiomodulation on vestibular toxicity. Slow harmonic acceleration (SHA) rotating platform testing was used for functional evaluation and both qualitative and quantitative epifluorescence analyses of cupula histopathology were performed. Animals were divided into gentamicin only and gentamicin plus laser treatment groups. Laser treatment was applied to one ear, and function and histopathology were evaluated in both ears. Decreased function was observed in both ears after gentamicin treatment, demonstrated by low gain and no SHA asymmetry. Laser treatment minimized the damage resulting from gentamicin treatment as shown by SHA asymmetry and recovered gain in the treated ear. Histology results reflected the functional results, showing increased hair cell density and epifluorescence intensity in laser-treated cupulae.

Narrow band CE-Chirp auditory steady-state response is more reliable than the conventional ASSR in predicting the behavioral hearing threshold.

OBJECTIVE: We evaluated conventional ASSR (Bio-logic MASTER II) and NB CE-Chirp ASSR thresholds as objective hearing measures in both normal and hearing loss subjects. METHODS: Patients with sensorineural hearing loss and volunteer normal hearing subjects were enrolled. Pure tone thresholds at 0.5, 1, 2 and 4 kHz were compared with the corresponding thresholds measured using Bio-logic MASTER II and the Eclipse ASSR systems. The threshold differences and correlation with pure tone were measured and reliability was evaluated with Cronbach's α. In part I of the study, all subjects were included, in part II of the study, only mild hearing loss and normal hearing subjects were included. RESULTS: In part I, NB CE-Chirp ASSR revealed a significantly smaller difference in threshold than conventional ASSR, a better correlation and better reliability. However, lower frequencies of NB CE-Chirp tended to be less reliable than higher frequencies. In part II, NB CE-Chirp revealed smaller threshold differences than conventional ASSR. Both correlation scores and reliability values were generally lower in the part II results. CONCLUSION: NB CE-Chirp ASSR generally revealed more favorable outcomes. However, its reliability was reduced at lower frequencies and in patients with milder hearing loss.

Simultaneous bilateral laser therapy accelerates recovery after noise-induced hearing loss in a rat model.

Noise-induced hearing loss is a common type of hearing loss. The effects of laser therapy have been investigated from various perspectives, including in wound healing, inflammation reduction, and nerve regeneration, as well as in hearing research. A promising feature of the laser is its capability to penetrate soft tissue; depending on the wavelength, laser energy can penetrate into the deepest part of the body without damaging non-target soft tissues. Based on this idea, we developed bilateral transtympanic laser therapy, which uses simultaneous laser irradiation in both ears, and evaluated the effects of bilateral laser therapy on cochlear damage caused by noise overexposure. Thus, the purpose of this research was to assess the benefits of simultaneous bilateral laser therapy compared with unilateral laser therapy and a control. Eighteen Sprague-Dawley rats were exposed to narrow-band noise at 115 dB SPL for 6 h. Multiple auditory brainstem responses were measured after each laser irradiation, and cochlear hair cells were counted after the 15th such irradiation. The penetration depth of the 808 nm laser was also measured after sacrifice. Approximately 5% of the laser energy reached the contralateral cochlea. Both bilateral and unilateral laser therapy decreased the hearing threshold after noise overstimulation in the rat model. The bilateral laser therapy group showed faster functional recovery at all tested frequencies compared with the unilateral laser therapy group. However, there was no difference in the endpoint ABR results or final hair cell survival, which was analyzed histologically.

Candidate's thesis: Platelet-activating factor-induced hearing loss: mediated by nitric oxide?

OBJECTIVES/HYPOTHESIS: Platelet-activating factor (PAF)in middle ear effusion is thought to induce hearing loss. The purpose of this study is to investigate the role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by studying the effects of PAF application on the round window membrane (RWM) with and without PAF-antagonist NO-blocker. STUDY DESIGN: Longitudinal study on randomized guinea pigs using PAF to induce hearing loss. METHODS Guinea pigs were divided into four groups: PBS, PAF, PAF-antagonist, and L-NAME. The PBS group received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and 40 microg of PAF soaked into gelfoam and placed on the RWM. PAF-antagonist (WEB 2170) and NOS inhibitor NG-nitro-l-arginine-methylester (L-NAME) were injected intraperitoneally prior to PAF 20 microg application on the RWM. The following three tests were performed on each animal group: Hearing was tested with an auditory brainstem response (ABR) test over 24 hours. At the end of 24 hours, cochlear hair cells were examined by scanning electron microscopy (SEM) and immunohistochemistry was carried out on the cochlea to test the expression of inducible nitric oxide synthase (iNOS). RESULTS: The PAF group developed significant elevation of ABR threshold and cochlear hair cell damage in the SEM group as compared with the PBS control group. The PAF-antagonist (WEB 2170) and the L-NAME groups did not show significant elevation of ABR threshold and cochlear hair cell damage compared with the group administered PAF 20 microg, but in the PAF-antagonist group, the elevation of ABR threshold was significant compared with that of the PBS control group, whereas it was not significant compared with the PBS group in the L-NAME group. Strong expression of iNOS on cochlea was observed in the PAF group and lighter expression was seen in PBS, WEB 2170, and L-NAME groups. CONCLUSIONS: This study demonstrated that PAF placed on the RWM induced hearing loss and cochlear hair cell damage. The PAF-antagonists and L-NAME prevented the PAF-induced hearing loss and inhibited iNOS expression in the cochlea. These findings suggest that the PAF-induced hearing loss caused by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and L-NAME may have future therapeutic implications in preventing sensorineural hearing loss associated with chronic otitis media. The results of this study have significant potential clinical application.

Clinical roles of fixation suppression failure in dizzy patients in the ENT clinic.

UNLABELLED: Abstract Conclusion: Any test for visual fixation suppression by itself is insufficient for screening central pathology and should be interpreted in conjunction with other neurotologic findings. OBJECTIVES: We evaluated the correlation of visual fixation suppression (VFS) under three different test conditions (spontaneous nystagmus, caloric stimulation, and slow harmonic acceleration, SHA), as well as the diagnostic accuracy of each test for predicting central pathology, in dizzy patients. METHODS: We retrospectively reviewed cases in a tertiary referral center; 504 consecutive dizzy patients who visited the ENT clinic were enrolled. The fixation index (FI, slow component velocity during fixation/slow component velocity before fixation × 100%) for the caloric test and spontaneous nystagmus was calculated and failure was indicated when the FI was greater than 60%. VFS during the SHA test at a frequency of 0.04 Hz was also performed and gain more than 0.2 was considered as failure of VFS. RESULTS: The incidence of VFS failure was 5.4% in the caloric test, 3.4% in spontaneous nystagmus, and 2.3% in the SHA test, respectively. Significant correlation was found only between the caloric test and the SHA test (r = 0.341, p < 0.001). The sensitivity of VFS in different tests did not exceed 35%. The specificity of VFS was highest (96.4%) in the 0.04 Hz SHA test, and exceeded 80% in the other tests.

Trans-canal laser irradiation reduces tinnitus perception of salicylate treated rat.

The aim of this study was to find out the effect of low-level laser therapy (LLLT) on salicylate-induced tinnitus in the rat model. Fourteen Sprague-Dawley rats (8 weeks; 240-280 gm) were divided into 2 groups (study group, control group). Rats of both groups were treated with 400 mg/kg/day of sodium salicylate for 8 consecutive days. Tinnitus was monitored using GPIAS (Gap Prepulse Inhibition of Acoustic Startle) 2 h after first salicylate treatment, and every 24 h during 9 days of treatment. Rats in laser group were irradiated to each ear with wavelength of 830 nm diode laser (165 mW/cm(2)) for 30 min daily for 8 days. During salicylate treatment, rats of study group irradiated with low level laser showed significantly higher GPIAS values throughout the experiment. Therapeutic effect of LLLT is demonstrated in animal tinnitus model by means of GPIAS. Further experimental studies are needed to find possible mechanisms and better methods to improve LLLT efficacy.

Effect of low-level laser treatment on cochlea hair-cell recovery after ototoxic hearing loss.

The primary cause of hearing loss includes damage to cochlear hair cells. Low-level laser therapy (LLLT) has become a popular treatment for damaged nervous systems. Based on the idea that cochlea hair cells and neural cells are from same developmental origin, the effect of LLLT on hearing loss in animal models is evaluated. Hearing loss animal models were established, and the animals were irradiated by 830-nm diode laser once a day for 10 days. Power density of the laser treatment was 900 mW/cm(2), and the fluence was 162 to 194 J. The tympanic membrane was evaluated after LLLT. Thresholds of auditory brainstem responses were evaluated before treatment, after gentamicin, and after 10 days of LLLT. Quantitative scanning electron microscopic (SEM) observations were done by counting remaining hair cells. Tympanic membranes were intact at the end of the experiment. No adverse tissue reaction was found. On SEM images, LLLT significantly increased the number of hair cells in middle and basal turns. Hearing was significantly improved by laser irradiation. After LLLT treatment, both the hearing threshold and hair-cell count significantly improved.

Characteristics of adverse effects when using high dose short term steroid regimen.

BACKGROUND AND OBJECTIVES: Although the adverse effect of long term steroid usage is well known, the adverse effect of short term high dose steroid usage has not been studied thoroughly. The purpose of this study was to identify the characteristics of the adverse effects when using a high dose steroid for a short term. We also compared the adverse effect of steroid between in- and out-patients. SUBJECTS AND METHODS: The medical record of 500 patients, who were treated with methylprednisolone 48 mg/day for 1-2 weeks, was retrospectively reviewed. Steroid was prescribed due to SSNHL, Bell's palsy, Ramsay-Hunt syndrome and herpes zoster oticus. The incidence of each adverse effect was analyzed, and also the time point of detection was analyzed. The 500 patients were composed of 250 in-patients and 250 out-patients. The adverse effect was compared between these two groups, as well. RESULTS: Adverse effect of steroid was found in 33.0% of the patients. Among these adverse effects, abdominal discomfort (26.8%) was most common, followed by skin rash (14.7%), swelling (13.4%), and hot flush (6.9%). Abdominal discomfort and hot flush was mostly detected on the first week. Meanwhile, the skin rash was usually detected on the third week. The incidence of adverse effect was significantly higher in the out-patient group. CONCLUSIONS: The incidence of high dose short term steroid treatment may be very high. The patients should be warned about these adverse effects. Monitoring should be performed until 3-4 week, since some adverse effects may not be detected until this time point.

Inflammation of temporomandibular joint increases neural activity in rat vestibular nucleus.

To determine whether the vestibular nuclei are affected by inflammation of temporomandibular joint (TMJ) region, we studied vestibular nucleus neural activity using two experimental groups: (1) normal saline 0.1cm(3) injection at right TMJ region, (2) 10% formalin 0.1cm(3) injection at right TMJ region. Neural activity after 24 hours was assessed by immunohistochemical staining with free-floating section at the level of interaural -1.30 mm to -2.00 mm for c-Fos. In inflammation group, formalin injection produced a bilateral increase in c-Fos at vestibular nucleus with ipsilesional side higher activity. In control group, expression of c-Fos protein was also observed in the vestibular nucleus (VN), especially MVN. But stain intensity of Fos-positive neurons was much weaker and mean number of c-Fos positive cells was fewer than inflammation group. This result suggests that there is a close neural connection between TMJ and vestibular nucleus, especially in case of inflammation.

Effect of low-level laser treatment on cochlea hair-cell recovery after acute acoustic trauma.

We investigated the effect of low-level laser radiation on rescuing hair cells of the cochlea after acute acoustic trauma and hearing loss. Nine rats were exposed to noise. Starting the following day, the left ears (NL ears) of the rats were irradiated at an energy output of 100 to 165 mW/cm(2) for 60 min for 12 days in a row. The right ears (N ears) were considered as the control group. Frequency-specific hearing levels were measured before the noise exposure and also after the 1st, 3rd to 5th, 8th to 10th and 12th irradiations. After the 12th treatment, hair cells were observed using a scanning electron microscope. Compared to initial hearing levels at all frequencies, thresholds increased markedly after noise exposure. After the 12th irradiation, hearing threshold was significantly lower for the NL ears compared to the N ears. When observed using an electron microscope, the number of hair cells in the middle turn of the NL ears was significantly larger than that of the N ears. Our findings suggest that low-level laser irradiation promotes recovery of hearing thresholds after acute acoustic trauma.

Antioxidant and anti-apoptotic effect of melatonin on the vestibular hair cells of rat utricles.

OBJECTIVES: Aminoglycosides are commonly used antibiotic agents, and they are known to generate free oxygen radicals within the inner ear and to cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Melatonin, a pineal secretory product, has the properties of being a powerful direct and indirect antioxidant. The aim of the present study was to prove the antioxidant effect of melatonin against gentamicin-induced ototoxicty. METHODS: The utricular maculae of Sprague-Dawley rats were prepared from postnatal day 2-4, and these maculae were were divided into 6 groups as follows: 1) control, 2) melatonin only, 3) gentamicin only, and 4), 5), and 6) gentamicin plus melatonin (10, 50, and 100 microM, respectively). To count the number of hair cells, 5 utricles from each group were stained with phalloidin-FITC on the 1st, 4th, and 7th days after drug administration. Reactive oxygen species (ROS) was assessed by using the fluorescent probe hydrofluorescent diacetate acetyl ester. The caspase-3 activity was also examined with using the fluorescent caspase-3 substrate and performing Western blotting. RESULTS: The result of this study showed that gentamicin induced the loss of utricular hair cells, and this loss of hair cells was significantly attenuated by co-administration of melatonin. Melatonin reduced ROS production and caspase-3 activation in the gentamicin treated utricular hair cells. CONCLUSION: Our findings conclusively reveal that melatonin has protective effects against gentamicin-induced hair cell loss in the utricles of rat by inhibiting both ROS production and caspase-3 activity.

In vitro and in vivo photodynamic therapy of otitis media in gerbils.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the antibacterial effects of photodynamic therapy (PDT) on common bacteria causing otitis media with effusion (OME). METHODS: An in vitro study was carried out using a hematoporphyrin derivative sensitizer (Photogem; Lemonosov Institute of Fine Chemical, Moscow, Russia) and a 632-nm diode laser on Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. The presence of colony-forming units of the bacteria was examined, the microscopic structures of the bacteria were examined by transmission electron microscopy (TEM), and flow cytometry of the bacteria was performed. An in vivo PDT study was performed using gerbils. S. pneumoniae or H. influenzae were injected into bullae. The Photogem was injected into the bullae 2 days later when OME developed, and transcanal irradiation with the 632-nm diode laser (90 J) was performed. Middle ear and bulla were washed with Dulbecco's phosphate buffered saline (DPBS) and the washed DPBS was cultured. The presence of bacterial colonies was examined. RESULTS: The PDT was effective in killing all three kinds of bacteria. TEM showed damaged bacterial cell membranes and cytoplasmic structures, and the flow cytometry showed a lower number of viable bacteria in the PDT group compared to the control group. PDT was effective in killing S. pneumoniae in 87% of the infected bullae with OME, whereas it was effective in eradicating H. influenzae in 50% of the infected bullae with OME. CONCLUSIONS: The results of these studies demonstrated that PDT may be effective to treat otitis media. PDT may have clinical implications in the treatment of otitis media that is resistant to antibiotic therapy.

Clinical characteristics of benign paroxysmal positional vertigo in Korea: a multicenter study.

Benign paroxysmal positional vertigo (BPPV) is characterized by episodic vertigo and nystagmus provoked by head motions. To study the characteristics of BPPV in a large group of patients in Korea, we retrospectively analyzed clinical features of 1,692 patients (women: 1,146, 67.7%; men: 54.6, 32.3%; mean age: 54.8+/-14.0 yr), who had been diagnosed as BPPV by trained neuro-otologists Dizziness Clinics. The diagnosis of BPPV was based on typical nystagmus elicited by positioning maneuvers. Posterior semicircular canal was involved in 60.9% of the patients, horizontal canal in 31.9%, anterior canal in 2.2%, and mixed canals in 5.0%. The horizontal canal type of BPPV (HC-BPPV) comprised 49.5% of geotropic and 50.5% of apogeotropic types. We could observe significant negative correlation between the proportion of HC-BPPV of each clinic and the mean time interval between the symptom onset and the first visit to the clinics (r=-0.841, p<0.05). Most patients were successfully treated with canalith repositioning maneuvers (86.9%). The high incidence of HC-BPPV in this study may be explained by relatively shorter time interval between the symptom onset and visit to the Dizziness Clinics in Korea, compared with previous studies in other countries.

Anticancer effect of combined intratumor cisplatin injection and interstitial KTP laser therapy on xenografted squamous cell carcinoma.

OBJECTIVE: This study was conducted to evaluate the synergistic effect of cisplatin and interstitial KTP laser therapy induced hyperthermia in vitro and in vivo (interstitial laser chemotherapy, ILCT). METHODS: In vitro study: human hypopharyngeal squamous carcinoma cell line (SNU-1041) was incubated in 1 mL of media containing various concentrations (0, 1, 2, 5, 10, 20, 50, 100 ng/mL) of cisplatin in 37 degrees and 43 degrees C for 2 hours. The viability of the cell was evaluated by MTT assay. In vivo study: human squamous cell carcinoma tumors were grown as subcutaneous transplants in nude mice and injected into tumor with cisplatin-epigel 100 microg, followed by interstitial laser therapy (ILT) via 0.6-mm diffuser fiber tips (532 nm, 1.0J/mm(3)). RESULTS: In vitro study: the viability of tumor cells incubated with 10 ng/mL of cisplatin was 62% and 28% in 37 degrees C and 43 degrees C, respectively (p = 0.02). In vivo study: the tumor volume in 4 weeks after treatment was 179 mm(3) in ILT group and 27 mm(3) in ILCT group. The ILCT group showed 8 (80%) complete remission of tumors at 4 weeks follow up, while tumor remission occurred in only 3 (30%) in ILT group (p < 0.05). CONCLUSION: These results suggest ILCT may become an effective treatment for head and neck carcinoma with minimal functional deficit.