An awareness and prevalence study of Irish cold-water athletes and external auditory canal exostoses.

OBJECTIVE: This study aimed to determine the awareness, otological symptoms and prevalence of external auditory canal exostoses in Irish cold-water athletes. METHOD: An online and in person cross-sectional survey was undertaken with Irish cold-water athletes to explore athletes' awareness, known prevalence of external auditory canal exostoses and attitudes towards preventive measures. RESULTS: Of the 926 participants surveyed, 67.5 per cent were aware of external auditory canal exostoses. Triathletes reported the lowest awareness (39.9 per cent) among water athletes. A total of 9.7 per cent (n = 90) had previously been diagnosed with external auditory canal exostoses and 46.7 per cent (n = 42) were non-surfers. Ear symptoms were reported in 76 per cent of athletes. Otoscopic examinations showed that 23.7 per cent had external auditory canal exostoses, 3.6 per cent of whom were aware of their diagnosis. CONCLUSION: The majority of Irish surfing athletes are aware of external auditory canal exostoses. There is less awareness with regard to Ireland's newly emerging sports such as open water swimming and triathlons. Over 90 per cent of athletes surveyed had no idea they had external auditory canal exostoses, which highlights the need to increase public awareness.

Visual outcomes after Phacoemulsification with Intraocular Implantation surgeries among patients with and without Diabetes Mellitus.

INTRODUCTION: The aim of this study was to compare the visual outcomes of phacoemulsification with intraocular lens implantation (IOL) surgery in patients with and without diabetes mellitus (DM) in Malaysia over a 12-year period and to identify factors that may contribute to poor visual outcome. MATERIALS AND METHODS: Data was retrieved from the webbased Malaysian Cataract Surgery Registry (CSR). Perioperative data for cataract surgery performed from 2007- 2018 were analysed. Inclusion criteria were age ≥40 years, phacoemulsification and IOL and senile cataract. Combined surgeries, surgeries performed by trainees and ocular comorbidities were excluded. Post-operative Best-Corrected Visual Acuity (BCVA) were compared. Factors affecting poor visual outcomes among those with DM were analysed using multivariate logistic regression to produce adjusted odds ratio (OR) for variables of interest. RESULTS: Total number of cases between 2007-2018 was 442,858, of whom 179,210 qualified for our analysis. DM group consisted of 72,087 cases (40.2%). There were 94.5% cases in DM group and 95.0Z from non-DM group who achieved BCVA ≥6/12 (p<0.001). Among patients with DM, advanced age (70-79 years old, OR: 2.54, 95% Confidence Interva, 95%CI: 1.91, 3.40; 80-89 years old, OR: 5.50, 95%CI: 4.02, 7.51), ≥90 years, OR: 9.77, 95%CI: 4.18, 22.81), poor preoperative presenting visual acuity [<6/18-6/60] (OR: 2.40, 95%CI: 1.84, 3.14) and <6/60-3/60 (OR: 3.00, 95%CI: 2.24, 4.02), <3/60 (OR 3.63, 95%CI: 2.77, 4.74)], presence of intraoperative complication (OR 2.24, 95%CI: 1.86, 2.71) and presence of postoperative complication (OR 5.21, 95%CI: 2.97, 9.16) were significant factors for poor visual outcome. CONCLUSIONS: Visual outcomes following phacoemulsification with IOL implantation surgery among cases with DM were poorer compared to cases without DM. Risk factors for poor visual outcomes among cases with DM were identified.

Persistence of solifenacin therapy in patients with overactive bladder in the clinical setting: a prospective, multicenter, observational study.

OBJECTIVES: The aim of this study was to evaluate the persistence with solifenacin therapy over a 12-month period in patients with overactive bladder (OAB). METHODS: This is a 52-week long, multicenter, prospective, observational study. The subjects were individuals ≥ 18 years old with OAB symptoms for ≥ 3 months, characterised by a total OAB Symptom Score (OABSS) of ≥ 3 and OABSS urgency item score of ≥ 2. Patients were prescribed 5 mg or 10 mg of solifenacin once daily for OAB symptoms. Drug persistence, reasons for discontinuation and factors related to the persistence were evaluated. RESULTS: A total of 1018 patients (329 men, 689 women) with a mean age of 59 years were included. The 52-week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36 weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in 13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94, 95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month period than were younger, male patients. The number of nocturia episodes was negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71-0.97). CONCLUSIONS: There was low persistence (22%) to solifenacin therapy for OAB symptoms over a 12-month period. Older patients, female patients and those with fewer episodes of nocturia were more persistent to therapy than were others.

Interventions do not enhance medication persistence and compliance in patients with overactive bladder: a 24 weeks, randomised, open-label, multi-center trial.

OBJECTIVES: Anticholinergics are currently the mainstay for the management of overactive bladder (OAB). However, low drug adherence has been noted with these medications. The aim of this study was to determine whether a health education intervention (HEI) could improve drug persistence with anticholinergics in OAB patients. METHODS: We enrolled 682 OAB patients who were randomly distributed into either the HEI plus fesoterodine (HEI) group or the fesoterodine alone (control) group. The HEI consists of four education sections: understanding OAB disease, dietary control, bladder training and understanding anticholinergics. The primary end-point was the difference in drug persistence between the HEI and control groups at 24 weeks. Persistence was defined as a gap ≤ 30 days between successive prescription pills. RESULTS: Among the 682 patients, 210 (30.8%) completed 24 weeks of study. Persistence of the HEI group at 6 months was not statistically higher than that of the control group (40.4% vs. 34.9%, p = 0.181). Compliance at 6 months was also similar between the two groups (38.5% vs. 32.5%, p = 0.128). Using OAB symptom score questionnaire, the efficacy of the two groups was not different at each follow-up (p > 0.05). The global response was similar between the two groups. However, the HEI group was more satisfied with treatment than the control group (p = 0.034). The most common reason for discontinuation was satisfaction with the treatment so that they did not need to follow-up, followed by inadequate efficacy in both groups. Adverse events were reported in 12.3% of patients. CONCLUSIONS: The health education intervention was not effective to increase drug persistence in OAB patients on anticholinergics.

The efficacy and tolerability of tarafenacin, a new muscarinic acetylcholine receptor M3 antagonist in patients with overactive bladder; randomised, double-blind, placebo-controlled phase 2 study.

OBJECTIVES: To evaluate the dose-response relationship of tarafenacin, an antimuscarinic agent in development phase, for efficacy and safety, at daily doses of 0.2 and 0.4 mg for the treatment of overactive bladder (OAB) PATIENTS AND METHODS: This multicentre, placebo-controlled, randomised, double-blind, phase 2b study was conducted. Patients were randomised to tarafenacin 0.2 mg, tarafenacin 0.4 mg or placebo daily for 12 weeks. Adult patients with OAB for at least 6 months, with an average of ≥ 8 micturitions per day and ≥ 3 incontinence episodes or a total of ≥ 6 urgency episodes per 3 days were enrolled. The primary objective was to compare the mean changes in the number of micturitions per 24 h of the two doses of tarafenacin compared with placebo from baseline to 12 weeks after treatment. RESULTS: A total of 334 patients were screened, of whom 235 patients were randomised. The mean decrease in the number of micturitions per 24 h from baseline to 12 weeks was statistically higher in the tarafenacin 0.4 mg group (-2.43 ± 2.21 times per day, p = 0.033) and non-statistically significant in the tarafenacin 0.2 mg group (-1.92 ± 2.45 times per day, p = 0.393) when compared with the placebo group (-1.77 ± 2.95 times per day). There were no statistically significant differences in the mean change of urgency episodes per 24 h among three groups. The most common adverse event was dry mouth. There were no significant differences in blurred vision and constipation compared with placebo. CONCLUSIONS: Tarafenacin 0.4 mg decreased the number of micturitions in patients with OAB after 12 weeks compared with placebo, and the dose-response relationship of tarafenacin 0.2 and 0.4 mg was confirmed. Both dose levels of tarafenacin were well tolerated.

A randomised, prospective double-blind, propiverine-controlled trial of imidafenacin in patients with overactive bladder.

AIM: To assess the efficacy and safety of imidafenacin compared with propiverine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: Patients with OAB symptoms were randomised to double-blind treatment with 0.1 mg of imidafenacin twice daily (group A) or propiverine 20 mg once daily (group B) for 12-week regimen, and assessed for efficacy and safety. The primary efficacy outcome was per cent change of weekly urgency urinary incontinence (UUI) episodes at week 12. The secondary efficacy outcomes were changes in the micturitions per day, urine volume voided per micturition, urgency episodes per day, complete disappearance of incontinence episodes and severity of urgency from baseline to week 12. Quality of life and safety profiles were also compared. RESULTS: Of 162 patients randomised, 140 completed the study protocol. The per cent change of weekly UUI episodes at week 12 was -69.1% in group A and -70.4% in group B (both p < 0.0001). The lower limit of 95% one-sided confidence interval of the difference between the groups was above the non-inferiority margin (-19.42%). Other voiding parameters and quality of life significantly improved at week 12 in both the groups. The discontinuation rates caused by adverse events were low in both the groups. While dry mouth was the most common adverse event (group A: 28.4% vs. B: 30.4%, p = 0.783), the severity of dry mouth was significantly less in the group A than B (p = 0.042) There were no significant differences in other safety profiles. CONCLUSIONS: After the 12-week treatment of imidafenacin 0.1 mg twice daily, all OAB symptoms and quality of life improved. Imidafenacin was not inferior to propiverine for the reduction of UUI episodes, and was better tolerated than propiverine in the safety profile. Our results indicate that imidafenacin is a safe and effective drug in Korean patients with OAB.

A randomised, double-blind, parallel design, multi-institutional, non-inferiority phase IV trial of imidafenacin versus fesoterodine for overactive bladder.

AIMS: Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder (OAB). METHODS: This study is a randomised, double-blind, parallel-group, fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months, daily mean voiding frequency (DMVF) ≥ 8, and daily mean urgency or urgency incontinence frequency ≥ 2. A twice-daily 0.1 mg imidafenacin with placebo, or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks. The primary efficacy end-point was the difference in DMVF at 12 weeks. The secondary efficacy end-points were differences in daily mean: (i) voiding frequency at 4 and 8 weeks; (ii) urgency frequency; (iii) urgency incontinence frequency; (iv) incontinence frequency; (v) nocturia frequency; and (vi) quality of life score. The variables for safety analysis were adverse events, vital signs, residual urine volume and clinical laboratory tests. An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients. RESULTS: The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups, respectively, and the difference was not significant between the two groups. Imidafenacin was non-inferior to fesoterodine, and the lower limit of 95% two-sided confidence intervals was -0.53. The other six secondary end-points and variables for safety analysis showed no difference between the two groups. CONCLUSIONS: Imidafenacin was non-inferior to fesoterodine in terms of efficacy, and showed no significant difference in terms of safety.

Patient-reported goal achievement after antimuscarinic treatment in patients with overactive bladder symptoms.

AIM: Standardised traditional outcome measures may fail to address factors that are important to patients and address irrelevant factors. Aim of this study was to assess patient-reported goals and goal achievement (GA) in the antimuscarinic treatment for overactive bladder (OAB) patients. METHODS: Men and women aged ≥ 18 years with OAB symptoms were eligible for the study. Treatment began with a dose of 10 mg oxybutynin, to be increased if necessary to 30 mg. Before treatment, each patient's primary treatment goal was identified. After 12-week treatment, patients reported GA using a Likert scale from 0 (no achievement) to 5 (complete achievement). Successful achievement was defined as a score of 4 or 5. Traditional outcome measures including voiding diaries, the OAB questionnaire short form, patient perception of bladder condition, and treatment benefit and satisfaction were assessed. Baseline characteristics affecting GA and the correlation between GA and traditional outcome measures were evaluated. RESULTS: A total of 303 goals were identified from 303 patients (51 men, 252 women). Of those, 72.3% addressed symptom relief and frequency as the most common target symptom. Other goals addressed were improving quality of life (13.5%) and eliminating coping behaviours (14.2%). After treatment, 42% had a successful GA with a median score of 3 (interquartile range; 2-4). Age had a negative effect on GA. Goal achievement was the outcome measure most correlated with treatment benefit and satisfaction. DISCUSSION AND CONCLUSIONS: Goal achievement can be a valuable outcome measure in OAB patients, addressing individual treatment goals and reflecting treatment benefit and patient satisfaction.

Prescription pattern of oxybutynin ER in patients with overactive bladder in real life practice: a multicentre, open-label, prospective observational study.

AIMS OF STUDY: To investigate the prescription pattern and dose distribution of the antimuscarinic agent oxybutynin extended release (ER) in patients with overactive bladder (OAB) in actual clinical practice. MATERIALS AND METHODS: In this multicentre, prospective, observational, flexible-dosing study, the dosage of oxybutynin ER for each patient was adjusted after discussions of efficacy and tolerability between doctor and patient, over a 12 week treatment period. Efficacy was measured by administering the Primary OAB Symptom Questionnaire (POSQ) before and after treatment. Patients were also administered, the patient perception of treatment benefit (PPTB) questionnaire at the end of the study. Adverse events (AE) were documented at each study visit. RESULTS: Of the 809 patients enrolled, 590 (73.2%) continued to take study medication for 12 weeks. Most patients were prescribed 5 (24.2%) or 10 (68.8%) mg/day oxybutynin ER at the start of treatment. Most were also prescribed 5 (19.1%) or 10 (67.4%) mg/day at the end of treatment, with a dose escalation rate of 14.9%. All OAB symptoms evaluated by the POSQ were improved; 94.1% of patients reported benefits from treatment and 89.3% were satisfied. Independent predictive factors for discontinuation were female, younger age (age ≤ 65), obesity (BMI ≥ 25), severe symptoms (USS, Gr. 5) and larger numbers of other co-medications. CONCLUSIONS: Most patients were prescribed 5-10 mg/day oxybutynin ER as both starting and maintenance doses, with a dose escalation rate of only 14.9%. Prescription of > 10 mg/day oxybutynin ER was not frequent in real life practice.

Symptom change after discontinuation of successful antimuscarinic treatment in patients with overactive bladder symptoms: a randomised, multicentre trial.

AIMS: Efficacy of antimuscarinic therapy for overactive bladder (OAB) has been demonstrated; however, the durability of its effects is unknown. The study was conducted to evaluate symptom change and retreatment rate after discontinuation of antimuscarinic therapy. Also, we tried to find risk factors for retreatment. METHODS: This was a prospective, randomised, open-label, multicentre trial at four university hospitals. Women who had OAB symptoms for ≥ 6 months and who showed successful response to 1 month of Tolterodine 4 mg medication were randomly assigned to one of three groups: (A) discontinue medication, (B) 2-month additional medication and (C) 5-month additional medication. After completion of the 1-, 3- or 6-month treatment, patients stopped the medication and were followed up for additional 3 months to assess symptom relapse and retreatment rates. Risk factors for retreatment were evaluated. RESULTS: Of a total of 558 patients who took the study medication, 173 were randomised and 108 (A: 40, B: 40, C: 28) were included in the analysis. At the end of the treatment, the mean micturition frequency was decreased to 8.3/24 h from 11.7/24 h, and the mean urgency episode was decreased to 2.2/24 h from 8.0/24 h. Three months after discontinuation, the micturition frequency and the urgency episode were increased to 9.1/24 and 4.4/24 h respectively. Sixty five per cent of patients requested retreatment, and 62% experienced symptom relapse. Baseline health-related quality of life was the only independent risk factor for retreatment. DISCUSSION AND CONCLUSION: Discontinuation of antimuscarinic therapy resulted in high symptom relapse and retreatment rates regardless of treatment duration. The results provide new information on the durability of the efficacy of antimuscarinics, and may improve treatment efficacy by promoting the medication persistence of antimuscarinics in OAB patients.

Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.

AIMS: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. METHODS: This was a 12-week, open-label, flexible-dose study of adults with OAB (> or = 8 micturitions and > or = 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject's and physician's subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. RESULTS: Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p < 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement > or = 2 points. Significant improvements from baseline (p < 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified. CONCLUSION: Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.

Arterial occlusion following embolization of an orbital arteriovenous malformation. A case report.

Orbital arteriovenous malformation is a rare condition which poses a management problem in view of the complexity of the vessels involved, and the potentially blinding and life-threatening complications from the modes of treatment. Treatment requires obliteration of the abnormal vascular communication. Vision may be adversely affected by the condition itself, as well as a result of invasive treatment modalities. This case reports such a situation where the visual outcome was severely affected following embolization of the feeding vessels.

CSF rhinorrhoea due to a pulsion diverticulum of the frontal horn.

We present the case of a 28-year-old man with cerebrospinal fluid (CSF) rhinorrhoea due to aqueduct stenosis and a pulsion diverticulum of the lateral ventricle into the frontal air sinus. He was successfully treated with an endoscopic third ventriculostomy and open repair of the defect.

Effects of nitric oxide synthases on detrusor overactivity after removal of bladder outlet obstruction in rats.

OBJECTIVES: Nitric oxide is a neurotransmitter that is related to overactive bladder. This study was undertaken to evaluate the expression of nitric oxide synthases (NOS) in relation to bladder function after the removal of the bladder outlet obstruction in rats. MATERIALS AND METHODS: 50 rats were divided into a control group (n = 10) and an experimental group (n = 40). The bladders in the experimental group were partially obstructed for 3 weeks. 3 weeks after removal, cystometrograms (CMG) were performed. On the basis of CMG results, the experimental group was subdivided into 'normalized' and 'overactive' groups. Expression of neuronal, inducible, and endothelial NOS mRNA in bladders of each group was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: On the CMG, the contraction interval of the overactive group was markedly decreased. RT-PCR results showed significantly decreased expression of nNOS and iNOS mRNA in the normalized group compared to the control group, and increased nNOS levels in the overactive group, compared to the normalized group (p < 0.05). A marked increase in eNOS mRNA expression was evident in the normalized and overactive groups compared to the control group (p < 0.05). CONCLUSIONS: Our results clearly show increases in nNOS and eNOS expression according to bladder function, which may be related to a persistently overactive bladder or irritative symptoms, following the removal of a bladder outlet obstruction.

Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study.

PURPOSE: We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of >or= 8 voids per 24 h and episodes of urgency or urgency incontinence >or= 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King's Health Questionnaire. RESULTS: A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively). CONCLUSIONS: Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.

Satisfaction with tolterodine: assessing symptom-specific patient-reported goal achievement in the treatment of overactive bladder in female patients (STARGATE study).

AIMS: Open-label study to evaluate the effect of tolterodine extended-release (ER) on symptom-specific patient-reported goal achievement (PGA) of overactive bladder (OAB) symptoms in females. METHODS: Eligible patients who had frequency >or= 8 and urgency >or= 2 episodes per 24 h with or without urgency incontinence were treated with 12-week tolterodine ER (4 mg once daily). Primary end-point was the rate of PGA by a visual analogue scale compared with initial expectation with treatment. At baseline, patients were asked to set their personal goals for each OAB symptom with treatment. Secondary efficacy variables were changes in symptom severity, voiding diary and patient perception of bladder condition (PPBC), global impression of improvement (GII), and willingness to continue treatment. RESULTS: A total of 56 patients were entered. The median rate of symptom-specific PGA and reductions in symptom severity were for frequency (60%, 45%), episodes of urgency 60%, 55%), urge incontinence (80%, 71%), nocturia (50%, 52%) and tenesmus (30%, 26%) after 12 weeks treatment. There was a significant improvement in all OAB symptoms in voiding diary. Thirty-five patients (62.5%) experienced an improvement of >or= 2 points in PPBC. Thirty (53.6%) and 22 (39.3%) of patients reported much and little improvement of their symptoms in GII. A total of 41 (73.2%) patients wanted to continue taking the medication at the end of the study. CONCLUSIONS: Most OAB patients reported improvement of their OAB symptoms with 12-week tolterodine ER 4 mg treatment. There was a significant achievement of symptom-specific goal on the key OAB symptoms. But, PGA did not correlate with objective outcomes.

Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.

We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-alpha (TNF-alpha) signalling pathways. Real-time reverse transcription-polymerase chain reaction showed that TNF-alpha mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF- but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-alpha-induced activation of MAPKs and Akt. In addition, TNF-alpha-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin alpha v, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-alpha-induced responses except for NF-kappaB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-alpha. These results suggest that the TNF-alpha signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.