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BACKGROUND AND OBJECTIVE: We evaluated inattention and behavioural outcomes following surgery versus watchful waiting (WW) in school-aged children with mild obstructive sleep apnoea (OSA). METHODS: A prospective randomized controlled study was performed in pre-pubertal children aged 6-11 years with polysomnography (PSG)-confirmed mild OSA. They were assigned randomly to early surgical intervention (ES) or WW. The surgical intervention consisting of tonsillectomy with or without adenoidectomy and turbinate reduction was carried out within 4-6 weeks after randomization. Both groups underwent PSG, attention and behavioural assessment and review by an otorhinolaryngologist at baseline and 9-month follow-up. The primary outcome was omission T score from Conners' continuous performance test (CPT). Secondary outcomes were parent-reported behaviours, quality of life, symptoms and PSG parameters. RESULTS: A total of 114 participants were randomized. Data of 35 subjects from the ES and 36 from the WW group were available for final analysis. No significant treatment effect could be found in all CPT parameters and behavioural outcomes. Nevertheless, significantly greater reductions were seen in PSG parameters (obstructive apnoea-hypopnoea index [-1.4 ± 2.0 cf. +0.3 ± 4.1/h, p = 0.038] and arousal index [-1.3 ± 4.4 cf. +1.4 ± 4.5/h, p = 0.013]) and OSA-18 total symptom score (-17.3 ± 19.7 cf. -3.6 ± 14.1, p = 0.001) in the ES group. Subjects who underwent surgery also had significantly greater weight gain (+3.3 ± 2.1 cf. +2.2 ± 1.5 kg, p = 0.014) and increase in systolic blood pressure (+5.1 ± 12.4 cf. -1.2 ± 8.7 mm Hg, p = 0.016). CONCLUSION: Despite improvements in PSG parameters and parent-reported symptoms, surgical treatment did not lead to parallel improvements in objective attention measures in school-aged children with mild OSA.
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Calidad de Vida , Apnea Obstructiva del Sueño , Adenoidectomía , Atención , Niño , Humanos , Estudios Prospectivos , Apnea Obstructiva del Sueño/cirugíaRESUMEN
OBJECTIVES/HYPOTHESIS: This study analyzes the treatment outcomes of frontal inverted papillomas (FIPs) in an attempt to provide guidelines for surgery selection. STUDY DESIGN: Retrospective case series. METHODS: The treatment results of 29 FIPs classified into five categories were retrospectively analyzed. The five categories are F1, tumor prolapsed into frontal sinus, tumor origin outside frontal sinus; F2, tumor origin inside frontal sinus, medial to the plane of lamina papyracea; F3, tumor origin inside frontal sinus, lateral to the plane of lamina papyracea; F4, bilateral; and F5, extrasinonasal. RESULTS: Of the 11 F1 cases, 73% had Draf I and 27% had Draf IIA procedures. There was one (9%) frontal recurrence and one (9%) frontal stenosis. Of the 10 F2 cases, 10% had Draf I, 40% had Draf IIA, 40% had Draf IIB, and 10% had Draf III surgery with a trephination. One patient (10%) had a frontal recurrence. Of the five F3 cases, 40% had Draf IIA surgery, 20% had external frontoethmoidectomy, and 40% had external frontal sinusotomy. The recurrence rate was 60%, and frontal stenosis rate was 60%. The two F4 cases had external frontal sinusotomies and Draf III surgery with no frontal recurrence or stenosis. The patient with the F5 had a frontal recurrence after Draf IIA surgery and external frontoethmoidectomy. CONCLUSIONS: Draf I or IIA surgery is adequate for most F1 tumors, and Draf II surgery is adequate for most F2 tumors. F3 and F4 tumors can be managed initially by Draf III surgery with external frontal sinusotomy added when required. F5 tumors probably require combined surgical approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1622-1628, 2020.
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Seno Frontal/cirugía , Recurrencia Local de Neoplasia/patología , Papiloma Invertido/patología , Neoplasias de los Senos Paranasales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Seno Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Papiloma Invertido/cirugía , Neoplasias de los Senos Paranasales/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To critically evaluate the use of endoscopic nasopharyngectomy in the treatment of recurrent nasopharyngeal carcinoma (NPC) through a case series, systematic literature review, and pooled analysis. METHODS: A case series of 18 patients combined with systematic literature review and pooled analysis of PubMed, Web of Science, and Scopus search, identifying 576 papers. After excluding 307 papers as search engine duplicates, only 16 of the remaining papers had adequate patient data to be included. RESULTS: Our case series of 18 patients had a 2-year disease-free survival (DFS) and overall survival (OS) of 90.0% and 100%, respectively. The pooled analysis of 300 patients that had an endoscopic resection of recurrent NPC showed recurrence-free survival and overall survival were 85.8% and 82.9%, respectively. Most, 56.1%, were recurrent T1 lesions. Resection margins were negative in 90.2% of patients. Local recurrence occurred in 20.1% of patients. Major complications occurred in 13.6% of patients. The mean hospital stay was 5.8 days, the mean operating time was 228.3 minutes, and the mean operative blood loss was 163 mL. CONCLUSION: Endoscopic resection of recurrent NPC occurs with low surgical morbidity. However, further long-term evaluation with longer follow-up data is needed to evaluate if the survival data is comparable or better than open approaches.
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Carcinoma/cirugía , Endoscopía , Neoplasias Nasofaríngeas/cirugía , Recurrencia Local de Neoplasia/cirugía , Faringectomía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Nasofaringe/cirugíaRESUMEN
OBJECTIVES/HYPOTHESIS: To evaluate the feasibility of a unique prototype foot-controlled robotic-enabled endoscope holder (FREE) in functional endoscopic sinus surgery. STUDY DESIGN: Cadaveric study. METHODS: Using human cadavers, we investigated the feasibility, advantages, and disadvantages of the robotic endoscope holder in performing endoscopic sinus surgery with two hands in five cadaver heads, mimicking a single nostril three-handed technique. RESULTS: The FREE robot is relatively easy to use. Setup was quick, taking less than 3 minutes from docking the robot at the head of the bed to visualizing the middle meatus. The unit is also relatively small, takes up little space, and currently has four degrees of freedom. The learning curve for using the foot control was short. The use of both hands was not hindered by the presence of the endoscope in the nasal cavity. The tremor filtration also aided in the smooth movement of the endoscope, with minimal collisions. CONCLUSION: The FREE endoscope holder in an ex-vivo cadaver test corroborated the feasibility of the robotic prototype, which allows for a two-handed approach to surgery equal to a single nostril three-handed technique without the holder that may reduce operating time. Further studies will be needed to evaluate its safety profile and use in other areas of endoscopic surgery. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:566-569, 2016.
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Endoscopía/métodos , Cavidad Nasal/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Robótica/instrumentación , Cadáver , Endoscopios , Estudios de Factibilidad , Pie , Humanos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The use of non-surgical treatment for childhood obstructive sleep apnea (OSA) is gaining popularity, especially in children with mild disease. OBJECTIVE: To test the hypothesis that intranasal corticosteroids reduce disease severity in children with mild OSA. STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial of intranasal mometasone furoate (MF) versus placebo in children aged 6 to 18 years with mild OSA. The primary outcome was the change from baseline obstructive apnea hypopnea index (OAHI), as documented by overnight polysomnography, after four months of treatment. RESULTS: Sixty-two children were recruited but 12 dropped out. This left 24 and 26 children for final analysis in the MF and placebo group, respectively. The OAHI and oxygen desaturation index (ODI) improved significantly in the MF group only. The OAHI decreased from 2.7 ± 0.2 to 1.7 ± 0.3 in the MF group, but increased from 2.5 ± 0.2 to 2.9 ± 0.6 in the placebo group (p = 0.039). The mean changes in ODI in the MF group and placebo group were -0.6 ± 0.5 and +0.7 ± 0.4, respectively (p = 0.037). CONCLUSION: Four months of treatment with intranasal mometasone furoate effectively reduces the severity of mild OSA in children.
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Antiinflamatorios/administración & dosificación , Furoato de Mometasona/administración & dosificación , Apnea Obstructiva del Sueño/tratamiento farmacológico , Tonsila Faríngea/patología , Administración Intranasal , Adolescente , Niño , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Tonsila Palatina/patología , Polisomnografía , Apnea Obstructiva del Sueño/patología , Resultado del TratamientoRESUMEN
BACKGROUND: The association between childhood OSA and endothelial function as measured by flow-mediated dilation (FMD) and its response to OSA treatment are uncertain. The objective of this study was to compare FMD in children with OSA with nonsnoring control subjects and to examine its response to treatment. METHODS: Index cases were children aged 6 to 18 years with habitual snoring and polysomnography (PSG)-confirmed OSA (obstructive apnea hypopnea index [OAHI] > 1 events/h). Each case was paired with an age-, sex-, and BMI-matched nonsnoring control subject recruited from our previous community growth survey. All subjects underwent FMD measurement in the morning after overnight PSG. Adenotonsillectomy (AT) was offered to subjects who satisfied predefined AT operation criteria. All cases underwent repeat PSG and FMD assessment 6 months later. RESULTS: A total of 63 case-control pairs were recruited. The OSA group had a significantly higher OAHI (median, 5.3 events/h [interquartile range (IQR), 2.6-11.7] vs 0.2 events/h [IQR, 0-0.5], P < .001) and lower FMD (mean ± SD, 7.9% ± 1.3% vs 8.3% ± 0.8%; P = .04) than the control group. Thirty-two case subjects underwent AT. A significant reduction in OAHI was documented in the AT group (-8.8 events/h [IQR, -13.7 to -4.7]; P < .001) accompanied by a significant increase in FMD (+0.6% [IQR, 0.4-1.4]; P < .001), which was not observed in subjects who did not undergo AT. CONCLUSIONS: Children with OSA had reduced FMD, which was reversible with treatment.
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Adenoidectomía , Endotelio Vascular/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Tonsilectomía , Vasodilatación/fisiología , Adolescente , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/fisiopatología , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Polisomnografía , Apnea Obstructiva del Sueño/cirugía , UltrasonografíaRESUMEN
BACKGROUND: The objective of this study was to examine the natural history of childhood primary snoring (PS) and to identify predictive clinical symptoms and risk factors associated with PS progression to obstructive sleep apnea (OSA). METHODS: Children aged 6 to 13 years old who received a diagnosis of PS in our previous community-based OSA prevalence study were invited to undergo repeat polysomnography (PSG) at 4-year follow-up. Subjects with an obstructive apnea hypopnea index (OAHI) ≥ 1 were classified as having OSA at follow-up. RESULTS: Seventy children (60% boys) with a mean age of 14.7 ± 1.8 years were analyzed in this follow-up study. The mean duration of follow-up was 4.6 ± 0.6 years. At follow-up, 26 subjects (37.1%) progressed to OSA, of whom five (7.1%) had moderate to severe disease (OAHI ≥ 5). Twenty-two (31.4%) remained at PS, and 18 (25.7%) had complete resolution of their snoring with normal PSG. Persistent snoring had a positive predictive value of 47.7% and a negative predictive value of 86.4% for progression from PS to OSA. Multivariate logistic regression analysis showed that persistent overweight/obesity was a significant risk factor for the development of OSA at follow-up, with an OR of 7.95 (95% CI, 1.43-44.09). CONCLUSIONS: More than one-third of school-aged children with PS progressed to OSA over a 4-year period, although only 7.1% developed moderate to severe disease. Weight control may be an important component in the management of PS because obesity was found to be a significant risk factor for PS progression.
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Apnea Obstructiva del Sueño/epidemiología , Ronquido/epidemiología , Adolescente , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Sobrepeso/epidemiología , Polisomnografía , Valor Predictivo de las Pruebas , Factores de Riesgo , Síndromes de la Apnea del SueñoRESUMEN
BACKGROUND: Suprasellar meningiomas often invade the optic canals (OCs). The feasibility of removing these tumors through a minimal-access endonasal route has been demonstrated, but the importance, safety, and timing of OC exploration and decompression are not well described. OBJECTIVE: To create a simple decision-tree algorithm for OC exploration and decompression in the endonasal endoscopic surgery for planum sphenoidale and tuberculum sella meningiomas. METHODS: We identified a consecutive series of 8 planum sphenoidale and tuberculum sella meningiomas resected endonasally. "Late" OC exploration and decompression was performed in 4 of 8 patients. The extent of resection, visual outcome, and complications were recorded. RESULTS: Five patients had OC invasion on magnetic resonance imaging. Endoscopic inspection did not reveal additional OC invasion. The OC was opened bilaterally in 2 patients and unilaterally in 2 patients. Gross total resection was achieved in 6 of 7 patients in whom it was the goal. Vision improved in 3 patients (3 of 3 OCs opened) and was stable in 4 (1 of 4 OCs opened). In 1 patient, the bitemporal hemianopsia improved, but there was unilateral deterioration (no OC invasion) because the tumor was extremely adherent to 1 optic nerve. After an average follow-up of 20.9 months, all patients had an Glasgow Outcome Scale score of 5, and there were no cerebrospinal fluid leaks. CONCLUSION: Exploration and decompression of the OC are feasible, safe, and important to optimize visual outcome and to minimize recurrence in planum sphenoidale and tuberculum sella meningiomas resected endonasally. It may not be important to open the canal early during surgery because tumor debulking can be performed without manipulating the optic nerves. Early decompression, however, is technically feasible.
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Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Neuroendoscopía , Quiasma Óptico/cirugía , Adulto , Anciano , Descompresión Quirúrgica , Femenino , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Quiasma Óptico/patología , Silla Turca/patología , Silla Turca/cirugíaRESUMEN
BACKGROUND: Epidermoid and dermoid cysts are uncommon entities that belong in the differential diagnosis of ventral skull base lesions. The endoscopic endonasal approach is an attractive option for management of these lesions with limited morbidity. The clinical characteristics and management course from our experience is reviewed along with the relevant literature. METHODS: A prospective database of endoscopic endonasal skull base cases performed since 2003 at a tertiary referral center was reviewed for cases involving keratinaceous lesions. Data on the pathology, radiology and management of the disease was reviewed. A search of pertinent literature using Medline was performed to complement the discussion. RESULTS: Three cases of intracranial keratinaceous cysts successfully managed with the endoscopic endonasal approach. All cases presented with headache, and 1 case presented with bitemporal hemianopsia. Characteristic appearance on magnetic resonance imaging was seen in each case. All lesions were intradural with variable involvement of the suprasellar, prepontine, and premedullary cisterns. Total resection was achieved in 2 cases and near total resection in 1 case. Postoperative cerebrospinal fluid leak occurred in one case, which was controlled after revision surgery using the "gasket-seal" technique. There were no cranial nerve palsies or vascular events. CONCLUSION: The endoscopic endonasal approach allows the rhinologic surgeon to access the ventral midline skull base for the successful management of keratinaceous cysts without major complications.
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Enfermedades Óseas/cirugía , Quiste Dermoide/cirugía , Endoscopía/métodos , Quiste Epidérmico/cirugía , Base del Cráneo/cirugía , Adulto , Femenino , Trastornos de Cefalalgia/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Cavidad Nasal/cirugía , Neoplasias de la Base del Cráneo/cirugíaRESUMEN
A 64-year-old man with a known history of diabetes and hypertension presented to the Accident and Emergency Department with a 2-day history of sudden decreased vision in the right eye. Temporal arteritis was suspected with an elevated erythrocyte sedimentation rate (71 mm/h), and oral prednisolone was started immediately. Four days later, the patient's right eye vision deteriorated from 0.6 to 0.05, with a grade-4 relative afferent pupillary defect and ophthalmoplegia. Computed tomography showed a contrast-enhancing orbital apex mass in the right orbit abutting the medial and lateral portions of the optic nerve with extension to the posterior ethmoid and sphenoid sinuses. A transethmoidal biopsy was performed which yielded septate hyphae suggestive of Aspergillus infection. Ten days later, the patient's right eye vision further deteriorated to hand movement with total ophthalmoplegia. MRI of the orbit showed suspicion of cavernous sinus thrombosis. A combined lateral orbitotomy and transethmoidal orbital apex drainage and decompression were performed to eradicate the orbital apex abscess. Drained pus cultured Aspergillus. The patient was prescribed systemic voriconazole for a total of 22 weeks. The latest MRI scan, performed 8 months after surgery, showed residual inflammatory changes with no signs of recurrence of the disease. To our knowledge, this is the first case report which describes the use of a combined open and endoscopic approach for orbital decompression and drainage in a case of orbital aspergillosis. We believe the combined approach gives good exposure to the orbital apex, and allows the abscess in this region to be adequately drained.
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Introduction The endoscopic endonasal approach to the parapharyngeal space (PPS) and jugular foramen is not well defined. We sought to systematically define the important landmarks and limitations of this new surgical technique using an endoscopic transmaxillary transpterygoid corridor. Methods Endoscopic dissection was performed in both sides of two latex-injected cadaver heads. Left-sided dissections were facilitated by the addition of a sublabial maxillary antrostomy. The pterygopalatine fossa, infratemporal fossa, and PPS were sequentially dissected and the endoscopic perspective was examined. Measurements were obtained from the surgical orifices to the upper cervical internal carotid artery (ICA) and internal jugular vein (IJV). Results Successful access to the PPS and jugular foramen was achieved in each dissection. The lateral pterygoid plate, mandibular branch of the trigeminal nerve, middle meningeal artery, levator veli palatini muscle, Eustachian tube, and stylopharyngeal fascia were identified as landmarks for the upper cervical ICA and the IJV. The mean distance from the nasal sill was markedly greater than from an ipsilateral sublabial antrostomy. Conclusion The endoscopic endonasal approach can provide adequate access to the PPS, carotid sheath, and jugular foramen. Multiple landmarks are useful to guide the dissection within these deep spaces and may facilitate the clinical application of this approach.
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BACKGROUND: The purpose of this study of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21, and p53 in sinonasal inverted papilloma (IP) was to help elucidate its pathogenesis. METHODS: Seventy-three IPs, 48 nasal polyps, and 85 hypertrophied turbinates were subjected to HPV polymerase chain reaction (PCR) study. Seventy-three IPs, 30 nasal polyps, and 32 hypertrophied turbinates were subjected to EBV in situ hybridization (ISH), p21, and p53 immunohistochemical (IHC) studies. RESULTS: HPV was positive in 3 of 73 IPs (4.1%). All specimens were EBV negative. In all, 99% of IPs showed strong and diffuse p21 nuclear reactivity. Most nasal polyps and hypertrophied turbinates showed weak to moderate immunoreactivity of the basal and parabasal cells. Only focal p53 immunoreactivity of the basal and parabasal cells was found in 19% of IPs and 40% of nasal polyps. CONCLUSIONS: HPV prevalence of our IP is low. EBV is not present in IP. High p21 and low p53 expression in IP suggests a non-p53-dependent regulation pathway.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Pólipos Nasales/metabolismo , Pólipos Nasales/virología , Papiloma Invertido/metabolismo , Papiloma Invertido/virología , Neoplasias de los Senos Paranasales/metabolismo , Neoplasias de los Senos Paranasales/virología , Proteína p53 Supresora de Tumor/metabolismo , Estudios de Cohortes , ADN Viral/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Herpesvirus Humano 4/aislamiento & purificación , Hong Kong/epidemiología , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Pólipos Nasales/epidemiología , Pólipos Nasales/genética , Papiloma Invertido/epidemiología , Papillomaviridae/aislamiento & purificación , Neoplasias de los Senos Paranasales/epidemiología , Neoplasias de los Senos Paranasales/genética , Reacción en Cadena de la Polimerasa/métodos , Prevalencia , Estudios Retrospectivos , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/genética , Infecciones Tumorales por Virus/metabolismo , Cornetes Nasales/metabolismo , Cornetes Nasales/patología , Cornetes Nasales/virologíaRESUMEN
BACKGROUND: The etiology of sinonasal inverted papilloma (IP) is unknown. This study was designed to evaluate the possible risk factors associated with IP Methods: This is a case-control epidemiology study in a tertiary referral center. Fifty patients with IP and 150 matched controls were interviewed using a questionnaire on suspected risk factors. Univariate analysis of the risk factors and calculation of the matched odds ratios, the corresponding 95% CIs, and p values was performed. Significant risk factors were further studied using conditional logistic regression analysis. RESULTS: Outdoor and industrial occupations were associated with IP. Tobacco smoking, drinking alcohol, history of allergic rhinitis, sinusitis, nasal polyp, non-sinonasal papilloma and non-sinonasal malignancy were not significant factors. CONCLUSION: Outdoor and industrial occupations were associated with IP and may be potential risk factors. Future studies are warranted to further evaluate the individual type of occupation and chemical involved.
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Neoplasias Nasales/epidemiología , Papiloma Invertido/epidemiología , Senos Paranasales/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasales/patología , Neoplasias Nasales/fisiopatología , Exposición Profesional , Papiloma Invertido/patología , Papiloma Invertido/fisiopatología , Factores de Riesgo , FumarRESUMEN
BACKGROUND: Early growth response-1 (Egr-1) is expressed in human airways and its polymorphisms have been associated with total IgE and atopy in asthmatic patients. We investigated the effects of Chinese-tagging single nucleotide polymorphism (SNP) of Egr-1 and its mRNA expression on allergic rhinitis (AR) traits. METHODS: Among 214 Chinese AR adults and 259 controls, tag SNP -4071 A-->G was genotyped and mRNA expression in peripheral blood was quantified by real-time PCR. RESULTS: Egr-1 mRNA expression was significantly higher in patients than controls (median of 0.23 vs 0.15 fold GAPDH expression; p<0.001). Its expression was not associated with -4071 polymorphism. However, significant correlations were found between -4071 A-->G with increased plasma total IgE (p=0.028) and atopy (p=0.030) in patients. Logistic regression confirmed the association (p=0.034) with age and gender adjusted. Patients homozygous for the A allele had a 2.3-fold and 1.9-fold risks, respectively of having increased plasma total IgE and atopy than those G allele carriers. CONCLUSIONS: We showed high levels of Egr-1 mRNA expression and demonstrated a significant association of polymorphism with increased plasma total IgE and atopy in AR patients. It may be useful to explore the pharmacogenetics of Egr-1 inhibitors.
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Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Inmunoglobulina E/sangre , Polimorfismo Genético , Rinitis Alérgica Perenne/genética , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Cartilla de ADN , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Rinitis Alérgica Perenne/sangreRESUMEN
BACKGROUND: The etiology of sinonasal inverted papilloma (IP) is unknown. This study was designed to evaluate the possible risk factors associated with IP Methods: This is a case-control epidemiology study in a tertiary referral center. Fifty patients with IP and 150 matched controls were interviewed using a questionnaire on suspected risk factors. Univariate analysis of the risk factors and calculation of the matched odds ratios, the corresponding 95% CIs, and p values was performed. Significant risk factors were further studied using conditional logistic regression analysis. RESULTS: Outdoor and industrial occupations were associated with IP. Tobacco smoking, drinking alcohol, history of allergic rhinitis, sinusitis, nasal polyp, non-sinonasal papilloma and non-sinonasal malignancy were not significant factors. CONCLUSION: Outdoor and industrial occupations were associated with IP and may be potential risk factors. Future studies are warranted to further evaluate the individual type of occupation and chemical involved.
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Clinical resistance to adriamycin (ADR) develops readily, and cardiotoxicity is a major dose-limiting side effect. A range of anthracycline derivatives have been synthesized recently, and a number reported to exhibit significantly reduced cardiotoxicity in experimental animals. Using NIL 8 Syrian hamster overy cells and two continuous human tumour cell lines derived from colon carcinomas we have screened a series of 11 anthracycline analogues, determining their in vitro cytotoxic effects by colony-forming assays. Five agents proved significantly more cytotoxic than ADR: dihydroxyanthraquinone (DHAQ), mitoxantrone (DHAD), 4-demethoxydaunorubicin (4-DNR), 4'-0-tetrahydropyranyl-adriamycin (THP-ADR), and 4'-deoxyadriamycin (4-ADR). We have also established in vitro a subline of the L5178Y murine lymphoma resistant to ADR and have used this model to identify derivatives with potential value for overcoming ADR resistance. We have observed three patterns of response: (i) complete cross-resistance with 4'-epiadriamycin and daunorubicin; (ii) slight cross-resistance with 4-DNR, THP-ADR, 7-con-O-methyl-nogarol and aclacinomycin A; and (iii) complete absence of cross-resistance with 4-ADR, 4'-O-methyladriamycin, DHAQ, DHAD, and methylhydroxyellipticinium. These straightforward preclinical screens thus identify three drugs which may merit clinical evaluation, since they not only show an increased level of cytotoxicity in vitro to ADR at equivalent concentrations but also overcome resistance to ADR in this murine model system.
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Antibióticos Antineoplásicos/farmacología , Ensayo de Unidades Formadoras de Colonias , Doxorrubicina/farmacología , Ensayo de Tumor de Célula Madre , Animales , Línea Celular , Cricetinae , Resistencia a Medicamentos , Humanos , Mesocricetus , Naftacenos/farmacologíaRESUMEN
Employing a tumourigenic mouse cell line, we have measured the effects of four anti-cancer drugs (methotrexate, vincristine, cis-platinum and adriamycin) upon tumour cell survival as assessed by three independent procedures. The results from two short-term procedures based upon dye exclusion and labeling index determinations were compared with data from the relatively long-term clonogenic or colony-forming assay. The dye exclusion procedure demonstrated the poorest correlation with the clonogenic assay, whereas labeling index measurements exhibited qualitative but not quantitative correspondence with results from the clonogenic assay. These short-term procedures cannot therefore be considered accurate substitutes for a clonogenic assay, which remains the method of choice for assessing cytotoxic effects of anti-cancer drugs.
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Antineoplásicos/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Células Clonales , Doxorrubicina/farmacología , Métodos , Metotrexato/farmacología , Ratones , Neoplasias Experimentales , Vincristina/farmacologíaRESUMEN
The effects of a range of anticancer drugs on murine neuroblastoma cells, used as a readily reproducible model system, have been compared by means of colony-forming assays and analyses by flow microfluorimetry (FMF). FMF provides the most rapid means of assessing the kinetic effects of drugs on cells. However, interpretation of these data is not clear-cut, since drug effects are highly dose-dependent and no distinction can be made easily between progression arrest and cell kill. Thus whilst FMF allows some qualitative assessment of the perturbing effects of cytotoxic drugs quantitative evaluation of cytotoxicity is still dependent on data from the more time-consuming cloning assays. However, when cells are treated with certain drugs, e.g., methotrexate, vincristine, or VM26, for only 1 h, negligible kill occurred as measured by colony formation. Therefore it appears necessary to prolong in vitro exposure time when testing these drugs or evaluating cytotoxicity of potential antitumour agents in vitro.