Quality of life after operative treatment of sinonasal inverted papilloma - a prospective study.

BACKGROUND: Studies assaying morbidity related to sinonasal inverted papilloma (SNIP) and its treatment are lacking. We evaluated how operative treatment of SNIP affects patients' health-related quality of life (HRQoL) and symptoms. METHODS: We prospectively recruited consecutive patients (n=52) operated for SNIP at Helsinki University Hospital, between years 2016 and 2019. In total, 42 patients filled in the 15D, a generic HRQoL instrument and a symptom questionnaire preoperatively and at 1 year and at 2 years postoperatively. The 15D HRQoL scores were compared to those of age- and sex-standardized general population. RESULTS: Patients' mean baseline score for discomfort and symptoms (one of the 15D dimensions) was significantly better compared to general population, but this difference faded postoperatively. Frequency of epistaxis, nasal obstruction, lowered sense of smell, headache, tinnitus and epiphora decreased significantly during follow-up whereas frequency of numbness of the face or mouth increased. Difference in the mean 15D score of the patients compared with general population was insignificant at baseline and at 1 year and at 2 years postoperatively. CONCLUSIONS: Measured by a generic HRQoL questionnaire, the mean score for discomfort and symptoms deteriorated after operative treatment of SNIP. Despite a relief of many symptoms, care should be taken when operating a benign tumour, as surgery may cause morbidity.

Patient injuries in operative rhinology during a ten-year period: Review of national patient insurance charts.

OBJECTIVES: To assess factors contributing to patient injuries in operative rhinology. DESIGN: Data of the accepted patient injury claims involving operative rhinology, between the years 2001 and 2011, were obtained from the Finnish Patient Insurance Centre registry. Two senior otolaryngologists analysed and evaluated the injury mechanisms. MAIN OUTCOME MEASURES: Analysis and classification of factors contributing to patient injuries. RESULTS: During the ten-year study period, there were 67 patient injuries in operative rhinology, comprising 36% of all patient injuries in otorhinolaryngologic surgery. The majority (78%) of patients were treated in university or central hospitals and almost all (90%) by fully trained otolaryngology specialists. The factors contributing to the injuries were errors in surgical technique, like lesions to the orbit, skull base and meninges, and adjacent nerves, as well as mistakes with removable packings left in situ. Nearly half of the patients had undergone endoscopic sinus surgery. One patient died because of bleeding from the intracranial artery. Fourteen patients (21%) needed a re-operation due to the injury. CONCLUSIONS: Patient injuries in rhinology were caused by typical complications of common operations performed by otorhinolaryngology specialists. The increased volume of endoscopic sinus surgery was evident also in patient injuries.

Association of breathing sound spectra with glottal dimensions in exercise-induced vocal cord dysfunction.

The objective of this study was to evaluate associations between the breathing sound spectra and glottal dimensions in exercise-induced vocal cord dysfunction (EIVCD) during a bicycle ergometry test. Nineteen subjects (mean age 21.8 years and range 13-39 years) with suspected EIVCD were studied. Vocal folds were continuously imaged with videolaryngoscopy and breathing sounds were recorded during the bicycle exercise test. Twelve subjects showed paradoxical movement of the vocal folds during inspiration by the end of the exercise. In seven subjects, no abnormal reactions in vocal folds were found; they served as control subjects. The glottal quotient (interarytenoid distance divided by the anteroposterior glottal distance) was calculated. From the same time period, the tracheal-vocal tract resonance peaks of the breathing sound spectra were analyzed, and stridor sounds were detected and measured. Subjects with EIVCD showed significantly higher resonance peaks during the inspiratory phase compared to the expiratory phase (p < 0.014). The glottal quotient decreased significantly in the EIVCD group (p < 0.001), but not in the control group. 8 out of 12 EIVCD patients (67%) showed stridor sounds, while none of the controls did. There was a significant inverse correlation between the frequencies of the breathing sound resonance peaks and the glottal quotient. The findings indicate that the typical EIVCD reaction of a paradoxical approximation of the vocal folds during inspiration, measured here as a decrease in the glottal quotient, is significantly associated with an increase in inspiratory resonance peaks. The findings are applicable in the documentation of EIVCD findings using videolaryngoscopy, in addition to giving clinicians tools for EIVCD recognition. However, the study is limited by the small number of subjects.

Towards better patient safety in otolaryngology: characteristics of patient injuries and their relationship with items on the WHO Surgical Safety Checklist.

OBJECTIVES: Increasing knowledge of factors contributing to medical adverse events has influenced the development of preventive policies and protocols, the WHO Surgical Safety Checklist being the most widely known. Despite growing evidence of the checklist's effectiveness in surgery, its role in preventing adverse events in otolaryngology is unclear. We assessed patient injury-contributing factors in otolaryngology and their relationship with WHO checklist items. STUDY DESIGN: A retrospective claim record study of national patient insurance charts in Finland. SETTING AND PARTICIPANTS: The records of all accepted patient injury claims in otolaryngology between 2001 and 2011 were searched and reviewed by two otolaryngologists. Operation-related injuries were evaluated in detail. Factors contributing to injury were identified, classified and compared with items on the WHO checklist. We also estimated whether the injury might have been prevented with a properly used checklist. RESULTS: In the 10-year study period, 188 (84.3%) of the 223 patient injuries were associated with operative care. Of these, 142 (75.5%) occurred in the operation theatre, and in 121 cases (64.4%), technical error in performing surgery was the primary cause of injury. In 18 injuries (9.6%), the error corresponded to a checklist item. Nine injuries (4.8%) could have been prevented with a properly used checklist. CONCLUSIONS: Patient injuries in otolaryngology are strongly related to operative care. The WHO checklist is one suitable tool for error prevention.

Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients.

Intralesional use of cidofovir (Vistide(®)) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.

The MDM2 promoter polymorphism SNP309T-->G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck.

BACKGROUND: MDM2 acts as a principal regulator of the tumour suppressor p53 by targeting its destruction through the ubiquitin pathway. A polymorphism in the MDM2 promoter (SNP309) was recently identified. SNP309 was shown to result, via Sp1, in higher levels of MDM2 RNA and protein, and subsequent attenuation of the p53 pathway. Furthermore, SNP309 was proposed to be associated with accelerated soft tissue sarcoma formation in both hereditary (Li-Fraumeni) and sporadic cases in humans. METHODS: We evaluated the possible contribution of SNP309 to three tumour types known to be linked with the MDM2/p53 pathway, using genomic sequencing or restriction fragment length polymorphism as screening methods. Three separate Finnish tumour materials (population based sets of 68 patients with early onset uterine leiomyosarcomas and 1042 patients with colorectal cancer, and a series of 162 patients with squamous cell carcinoma of the head and neck) and a set of 185 healthy Finnish controls were analysed for SNP309. RESULTS: Frequencies of SNP309 were similar in all four cohorts. In the colorectal cancer series, SNP309 was somewhat more frequent in women and in patients with microsatellite stable tumours. Female SNP309 carriers were diagnosed with colorectal cancer approximately 2.7 years earlier than those carrying the wild type gene. However, no statistically significant association of SNP309 with patients' age at disease onset or to any other clinicopathological parameter was found in these three tumour materials. CONCLUSION: SNP309 had no significant contribution to tumour formation in our materials. Possible associations of SNP309 with microsatellite stable colorectal cancer and with earlier disease onset in female carriers need to be examined in subsequent studies.

Supragastric belch may be related to globus symptom - a prospective clinical study.

BACKGROUND: The etiology of globus is poorly understood. It is controversial, whether gastroesophageal reflux disease (GERD) has a role in globus. To investigate the possible esophageal background of this symptom, we performed transnasal esophagoscopy (TNE), high-resolution manometry (HRM), and 24-h multichannel intraluminal impedance (MII) and pH monitoring on globus patients. METHODS: Thirty consecutive patients were referred to Helsinki University Hospital, Department of Otorhinolaryngology - Head and Neck Surgery for treatment of globus; 24 consecutive patients with difficult reflux symptoms from the Department of Surgery served as controls. We compared the results of the patient groups in endoscopies, HRM, and 24-h MII-pH monitoring. KEY RESULTS: In MII monitoring, globus patients had supragastric belch (6/20, 30% vs 1/24, 4%; p = 0.038) more often than controls. Total reflux time was higher in controls (p = 0.004), and they had more acid reflux events (p = 0.002) in MII, but between groups, the number of non-acid reflux events was similar. In pH monitoring, DeMeester score and total pH <4 time were higher in controls (P < 0.001). In HRM, the upper esophageal sphincter (UES) mean basal and residual pressures did not differ. CONCLUSIONS & INFERENCES: Supragastric belch was more common in globus patients, suggesting the possible role of this condition in globus sensation. However, globus patients in this series had no acid or non-acid GERD or elevated UES pressure.

A new quantitative PCR for human parvovirus B19 genotypes.

Parvovirus B19 (B19V) is a minute ssDNA virus associated with a wide range of diseases from childhood erythema to fetal death. After primary infection, the viral genomes persist lifelong in solid tissues of most types. Quantification of the viral DNA is important in the timing of primary infection, assessment of tissue persistence and screening of blood donor plasma. In this study, we present a new PCR assay for detection and quantification as well as for differentiation of all three B19V genotypes. A new B19V qPCR was designed to target a 154-bp region of the NS1 area. Serum, plasma and solid tissue samples were suitable for testing in the assay. The WHO International Reference Panel for Parvovirus B19 Genotypes was utilized to validate the assay for detection of different genotypes of B19V in clinical material. Each panel member yielded, by the new qPCR, a quantity similar to the one reported by National Institute for Biological Standards and Control (NIBSC). The qPCR was specific for B19V and amplified and quantified all three genotypes with detection sensitivities of ≤10 copies/reaction. The differentiation of B19V genotypes was performed by Sanger sequencing of the amplified products.

A novel method to culture laryngeal human papillomavirus-positive epithelial cells produces papilloma-type cytology on collagen rafts.

A novel method to culture human papillomavirus (HPV) positive laryngeal epithelial cells is described. Biopsies of laryngeal papillomas and of HPV-positive laryngeal mucosa were first cultured as a monolayer in which irradiated laryngeal fibroblasts originally derived from a papilloma (PPLF-XR) patient served as feeder cells. When these fourth or fifth passage epithelial cells were transferred to allow growth on an organotypic growth base (collagen raft containing unirradiated PPLF), they grew as a multilayer. This layer showed features typical of HPV infection with koilocytosis, parakeratosis, and isolated dyskeratotic cells. Based on in situ hybridisation, the original tumour sections and epithelial cells from each monolayer passage, as well as the collagen raft sections, contained HPV DNA. Our results show that HPV-infected epithelial cells can be maintained during passages in monolayer culture and that PPLF can support the growth of these cells well. The monolayer cell culture and the collagen raft, the latter providing differentiation-promoting effects, appears to facilitate maintenance of the infected cells and of the viral genome.

Establishment and characterisation of human papillomavirus type 16 DNA immortalised human tonsillar epithelial cell lines.

Oncogenic human papillomavirus (HPV) plays a possible aetiological role in a subset of head and neck cancers, particularly in tonsillar carcinomas. For establishing a model to study mechanisms involved in HPV-associated tonsillar carcinogenesis, normal human tonsillar epithelial (HTE) cells were transfected with full-length HPV-16 DNA. The transfections produced four immortalised cell lines, designated HTE-114/K1, HTE-114/K2, HTE-114/K3 and HTE-114/B. All transfected HTE cell lines were cytogenetically abnormal. They exhibited altered morphology and impaired expression of cytokeratins in organotypic cultures. They failed to form colonies in soft agarose and formed no tumours in nude mice within 6 months. Each of them contained integrated viral DNA in a distinctive pattern as shown by Southern blot hybridisation. Early viral transcripts containing the E7 gene were detected by northern blot hybridisation. In conclusion, primary HTE cells can be immortalised following transfection with full-length HPV-16 DNA; the immortalised cell lines had partially retained epithelial characteristics in their morphology and function. They seem to represent early stages of premalignant epithelial cells and thus provide a useful model for studying further the multistep molecular events of HPV-16-associated tonsillar carcinogenesis.

Poor antibody response against human papillomavirus in adult-onset laryngeal papillomatosis.

To investigate whether adult-onset laryngeal papillomatosis induces serum antibodies to the human papillomavirus (HPV), 60 patients underwent a clinical examination, and HPV DNA from their laryngeal biopsy was assayed by PCR and HPV serology with virus-like particles as the antigen. Patients and controls (n = 53) showed no differences in their HPV 6 and 16 antibodies. Patients more often had HPV 11 antibodies, female patients more often than female controls or male patients. Of the female patients, 5 of 15 had a history of genital condylomas and, at the follow-up visit, 5 of 9 had cervical cytology consistent with genital HPV infection. The fact that HPV antibodies did not correlate with clinical features of the laryngeal disease or with HPV DNA detected in the larynx, suggests that HPV antibodies in female patients were induced by genital rather than laryngeal HPV infection. The high prevalence of abnormal Pap smears indicates that gynaecological examination of female adult-onset laryngeal papilloma patients is warranted.

HLA-DRB1, -DQB1 alleles in head and neck carcinoma patients.

Certain HLA class II alleles have been reported to play a role in development or prevention of cervical carcinoma, an epithelial malignancy linked to human papillomavirus (HPV). In head and neck carcinomas, of which a subset is also HPV associated, the impact of HLA genes remains unknown. HLA-DRB1, -DQB1 alleles were determined in a comprehensive series of 162 head and neck carcinoma patients, for which 83 consecutive cadaveric organ donors of Finnish origin served as controls. DRB1*03 was associated with node-negative disease and DRB1*08 and 13 with small tumors; DRB1*04 was protective against disease relapse. Most alleles of borderline significance in this study act similarly in cervical carcinomas.

Postoperative infection following nasal septoplasty.

This retrospective study evaluates the incidence and spectrum of infectious complications in 100 consecutive adult nasal septoplasty patients. A total of 12 patients (mean age 40 years; age range 24-55 years) suffered from postoperative infection, and 3/12 had received prophylactic antibiotics. Patients presented with abscess formation (n = 7), submucosal swelling and flush (n = 4) and haematoma and high fever (n = 1). None of the patients had life-threatening complications, such as meningitis, endocarditis or septic/toxic shock. After surgical drainage, antibiotic treatment was given orally or intravenously. The mean hospitalization time was 3.6 days. To assess the clinical outcome, 8/12 patients were re-examined about 1.8 years after the operation. They all had an improved rhinological status. Septoplasty had been successful in relieving nasal obstruction in seven (88%) patients. Staphylococcus aureus was isolated from the nasal mucosa in three (38%) patients, which is in line with previous findings in healthy nasal septoplasty patients. The use of antimicrobial prophylaxis in septal surgery will be discussed.

Human papillomavirus in laryngeal papillomas and in adjacent normal epithelium.

Eleven adults with laryngeal papillomas were studied for the presence of human papillomavirus (HPV) DNA by in situ hybridization. As well as from the papillomas, three additional biopsies were taken from the normal-appearing mucosa as follows: the involved vocal cord, the opposite vocal cord (when the papilloma was unilateral), and from the ventricular fold on the side of the lesion. These normal tissues were analysed by polymerase chain reaction (PCR) to detect HPV DNA. All except one of the 11 papillomas contained HPV DNA; nine were HPV 6/11 DNA positive and one positive for HPV 16 DNA. The normal-appearing laryngeal mucosa harboured HPV DNA in eight out of 11 patients. The present results strongly support the concept that the adult-type laryngeal papilloma is an HPV-induced lesion, mostly due to HPV types 6 and 11. The persistence of HPV DNA in the adjacent normal epithelium is consistent with the frequent recurrence of these lesions.

Prognostic value of clinical findings in histologically verified adult-onset laryngeal papillomas.

A retrospective study of adult-onset laryngeal papilloma was performed to clarify whether any clinical features at the time of diagnosis could predict its course. All patients had a histologically confirmed diagnosis of laryngeal papillomas and were treated at Helsinki University Hospital between 1975 and 1994. Those with adult-onset disease and follow-up exceeding 1 year (n = 74) entered the study. Based on the case records surveyed, results suggested two risk factors for frequent laryngeal procedures: young age at onset of papilloma and a lesion extending to the anterior third to the vocal folds. It was not possible to predict the course of the disease by such clinical findings as symptoms or size or number of primary papilloma lesions. As regards the recurrence of disease, the classic division of adult-onset laryngeal papilloma into solitary and multiple type was not found to be clinically relevant.

IgG subclass distributions in anti-hapten and anti-polysaccharide antibodies induced by haptenated polysaccharides.

Mice were immunized with hapten [NIP, (4-hydroxy-5-iodo-3-nitrophenyl)acetyl or TNP (2,4,6-trinitrophenyl)] conjugates of Ficoll or pneumococcal polysaccharide type 14 (S14), and they were bled on days 10 or 14. Anti-hapten and anti-polysaccharide antibodies were determined from the sera or from fractions (IgM + IgA). IgG1, IgG2a, IgG3 or IgG2b separated by a gradual acid elution from protein A. Approximately one-half of both anti-hapten and anti-polysaccharide antibodies was found in the IgM + IgA fraction. The subclass distribution of the IgG antibodies was dependent on the antigenic determinants. Polysaccharide antibodies were mostly in the IgG3 fraction (36-62%) and in the IgG1 fraction (18-36%). Hapten IgG antibodies were mostly in the IgG1 fraction (38-74%): each of the other three subclasses contributed the average of 13%. These results provide the first evidence that antibodies to different determinants of one antigen have grossly different isotype distributions.