Leena-Maija Aaltonen

First year with WHO Surgical Safety Checklist in 7148 otorhinolaryngological operations: use and user attitudes

Dear Editor, The World Health Organisation (WHO) developed The Surgical Safety Checklist to improve patient safety in the operating room (OR) (http://www.who.int/patientsafety/ safesurgery/en/index.html). This checklist has reduced complications and deaths significantly. The checklist has taken into use in various surgical surroundings around the world. We have recently reported promising preliminary experiences of the checklist in otolaryngology. The aim of this study was to evaluate use activity and user opinions about the checklist in otolaryngology 1 year after its implementation. In addition, we wanted to assess safety attitudes within an operating department.

Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck

Fresh‐frozen biopsies were obtained from 61 patients at diagnosis of squamous cell carcinoma of the head and neck (HNSCC) for study of the prevalence and physical status of human papillomavirus (HPV) DNA. The frequency of HPV DNA and genotypes were determined by SPF10 PCR screening with a general probe hybridization and INNO‐LiPA HPV genotyping assay. In addition, a single‐phase PCR with primers FAP 59/64 and a nested PCR with primers CP 65/70 and CP 66/69 served to detect particularly cutaneous HPV types. By the sensitive SPF10 PCR and INNO‐LiPA assay, 37 of 61 (61%) samples were positive for HPV. HPV‐16 was the most frequently detected type (31 of 37, 84%). Multiple infections were found in 8 of 37 (22%) of the HPV‐positive samples, and co‐infection by HPV‐16 and HPV‐33 was predominant. No cutaneous HPV types were detected. Patients with HPV‐positive tumors had similar prognosis as those with HPV‐negative ones. Real‐time PCR analysis of the HPV‐16 positive samples indicated the presence of integrated (11 of 23, 48%), episomal (8 of 23, 35%) and mixed forms (4 of 23, 17%) of HPV DNA. The viral load of HPV DNA exhibited large variation. The median copy numbers of E6 DNA in tonsillar specimens were approximately 80,000 times higher than that in nontonsillar HNSCC ones. Patients with episomal viral DNA were more frequently found to have large (T3–T4) tumors at diagnosis than were those with integrated or mixed forms.

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.

Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency

Abstract Background Merkel cell polyomavirus (MCPyV) was discovered recently. It is considered a potential causative agent of Merkel cell carcinoma, a life-threatening skin cancer. Objectives To study the prevalence of MCPyV in a large number of clinical samples of various types. Most of the samples were examined also for the other newly found polyomaviruses KI (KIPyV) and WU (WUPyV). Study design Altogether 1390 samples from immunocompetent or immunocompromised patients, including (i) tonsillar tissues and sera from tonsillectomy patients; (ii) nasopharyngeal aspirates (NPAs) and sera from wheezing children and (iii) nasal swabs, sera and stools from febrile leukemic children were studied for MCPyV. The tonsils, nasal swabs and stools were also studied for KIPyV and WUPyV. Results MCPyV DNA was detected in 14 samples altogether; 8 of 229 (3.5%) tonsillar tissues, 3 of 140 (2.1%) NPAs, 2 of 106 (1.9%) nasal swabs and 1 of 840 (0.1%) sera. WUPyV and KIPyV were detected in 5 (2.2%) and 0 tonsils, 1 (0.9%) and 4 (3.8%) nasal swabs and 0 and 2 (2.7%) fecal samples, respectively. The patients carrying in tonsils MCPyV were of significantly higher age (median 42years) than those carrying WUPyV (4years, p <0.001). Conclusions MCPyV DNA occurs in tonsils more frequently in adults than in children. By contrast, WUPyV DNA is found preferentially in children. MCPyV occurs also in nasal swabs and NPAs, in a frequency similar to that of KIPyV and WUPyV. The tonsil may be an initial site of WUPyV infection and a site of MCPyV persistence.

Human Papillomavirus in Larynx

Objectives The core of the present clinical and basic research knowledge of laryngeal human papillomavirus (HPV) infection is described.

Presence of DNA of Human Papillomavirus 16 but No Other Types in Tumor-Free Tonsillar Tissue

ABSTRACT According to PCR, the prevalences of human papillomavirus (HPV) DNA were 6.3% (13 of 206) in tonsillitis or hypertrophic tonsillar tissues and 0.6% (1 of 174) in exfoliated cells from normal tonsils. HPV-16 was the only type detected in tonsillar tissues, but it did not appear to lead to L1 antibody production.

Fiberoptic videolaryngoscopy during bicycle ergometry: A diagnostic tool for exercise-induced vocal cord dysfunction

Exercise‐induced vocal cord dysfunction is difficult to diagnose because the paradoxical vocal cord adduction should be observed during exercise. Our goal was to develop and validate a new diagnostic method for exercise‐induced vocal cord dysfunction by combining continuous fiberoptic laryngoscopy with a bicycle ergometry test.

Postlaryngectomy Voice Restoration Using a Voice Prosthesis: A Single Institution's Ten-Year Experience

We describe the speech rehabilitation outcome of patients treated with total laryngectomy or total laryngopharyngectomy and insertion of Provox voice prostheses (Atos Medical AB, Hörby, Sweden) at the Helsinki University Central Hospital. We performed a retrospective chart review of 95 patients (88 men and 7 women; mean age, 63.5 years) who underwent insertion of a voice prosthesis in the period 1992 to 2002. Eighty-one percent (77/95) of the patients underwent a primary prosthesis insertion at the time of laryngectomy. A head and neck surgeon, a laryngologist, and a speech therapist rated the long-term tracheoesophageal speech of 78% (74/95) of the patients as good or average. The main causes for replacement of the device were obstruction, leakage or inadequate size of the prosthesis, and granulation or leakage around the fistula. According to our 10-year experience, use of the Provox prosthesis is an effective method of postlaryngectomy voice rehabilitation, and it continues to be our preferred method of voice restoration in the majority of cases.

Epidermal growth factor receptor domain II, IV, and kinase domain mutations in human solid tumors

Mutations that may predict response to adenosine 5′-triphosphate (ATP)-mimetic epidermal growth factor receptor (EGFR) inhibitors occur in the EGFR kinase domain in lung adenocarcinomas and bronchioloalveolar carcinomas (BACs). Data on the frequency of EGFR mutations are sparse in other human tumors. Apart from the deletion mutant EGFRvIII, little is known about the frequency of mutations that encode for the EGFR extracellular domains II and IV that participate in receptor dimerization and formation of the tethered (autoinhibited) receptor conformation. We investigated 566 human neoplasms consisting of various histological types for mutations in exons 6, 7 (encode domain II), 14, 15 (domain IV), 18, 19, and 21 (the kinase domain) using denaturing high-performance liquid chromatography (DHPLC). Approximately 4,500 EGFR exons were screened for the presence of a mutation, and samples with an abnormal finding in DHPLC were sequenced. Only one mutation was found in the extracellular domain IV (glioblastoma), and none in domain II. Eight (11%) out of the 40 lung adenocarcinomas, or 33 BACs, investigated had exon 19 or 21 mutation in the kinase domain, but no mutations were found in other tumor types. Most of the lung cancers with mutated EGFR had three to six copies of the mutated gene in fluorescence in situ hybridization. We conclude that mutations of the EGFR kinase domain and the cysteine-rich extracellular domains are infrequent in most types of human cancer apart from lung adenocarcinoma. Mutated EGFR is usually not amplified in lung cancer.

Detection of TS polyomavirus DNA in tonsillar tissues of children and adults: evidence for site of viral latency.

BACKGROUND The trichodysplasia spinulosa-associated polyomavirus (TSPyV), a recently discovered species of the family Polyomaviridae, is associated with development of trichodysplasia spinulosa (TS), a rare follicular skin disease of immunocompromised individuals. The viral seroprevalence in the general population is ∼70%, with little known of its route of transmission, latency, or primary infection site. OBJECTIVES We aimed to determine whether the viral DNA is detectable in tonsillar tissue of constitutionally healthy individuals, and what the corresponding antiviral seroreactivities are. STUDY DESIGN We tested 229 matched pairs of tonsillar tissue biopsies and serum samples from asymptomatic donors for TSPyV DNA by real-time quantitative PCR with primer pairs and Taq-Man probes targeting the VP1 and LT genes. The sera were studied by enzyme immunoassay (EIA) for TSPyV-VP1-IgG and the PCR-positive individuals also for -IgM and -IgG-avidity. RESULTS TSPyV DNA was detectable in 8 (3.5%) of 229 tonsillar tissues, and in none of the corresponding sera. TSPyV IgG seroprevalence among children was 39% and among adults 70%. Each of the 8 PCR-positive subjects had antiviral IgG of high avidity but not IgM. CONCLUSIONS TSPyV PCR positivity of tonsillar samples of individuals with long-term immunity provides the first evidence of TSPyV in tonsils and suggests lymphoid tissue as a latency site of this emerging human pathogen.