Computer-assisted quantitative image analysis of cell proliferation, angiogenesis and stromal markers in experimental and laryngeal tumor development

Abstract Automated quantitative computer-assisted morphometric analysis of immunohistochemical expression of markers of neoplastic development and progression in experimentally induced and in human neoplasms showed very high sensitivity and reproducibility, allowing analysis of large numbers of cell and tissue components. Totals of 26 million pixels, 25,000 cells and 1500 vessels were examined, with a sensitivity exceeding 99% and reproducibility exceeding 99%. The total expression of proliferating cell nuclear antigen (PCNA) and p53 increased consistently during 7H-dibenz[c, g] carbazole (DBC)-induced formation of dysplasias and squamous cell carcinomas (SCC:s) in hamster lung. In dysplasia, nuclear size and PCNA staining intensity increased; in SCC:s nuclear size decreased. In a retrospective study on archival material of human laryngeal squamous cell carcinomas, the occurrence and location of PCNA-positive cells were specifically related to the degree of differentiation. In SCC:s nuclear size decreased, while shape alterations and PCNA staining intensity increased in relation to degree of malignancy. In DBC-induced respiratory carcinogenesis increased collagen matrix synthesis occurred prior to neoplasm development. Among squamous cell carcinomas, in well-differentiated tumors, collagen deposition increased, as did fiber size, in moderately differentiated tumors collagen synthesis and the deposition of new collagen decreased. The increase in transforming growth factor beta expression in differentiated cells and in the matrix was isoform-specific. Increased angiogenesis in laryngeal tumor development occurred in preneoplastic states and in SCC: s, inversely related to the degree of differentiation. In well-differentiated neoplasms the vessels were lying in the direction of the BM, in moderately differentiated neoplasms vessels were lying in the direction of tumor invasion and in poorly differentiated neoplasms irregular, partly abnormal vessels intermixed with tumor cells. Small regular vessels predominated in benign conditions and large, irregular vessels in malignant conditions. Experimental models provided the advantage of examining homogenous, well-characterized neoplasm progression without interfering with the process. Morphometric methods provided detailed information on large numbers of cells, useful for studies of tumor behavior and with potential clinical applications

Development of otology specific outcome measure:Ear Outcome Survey-16 (EOS-16)

Abstract Purpose: An important outcome measure of patient care is the impact on the patient’s health-related quality of life (HRQoL). Current ear-specific HRQoL instruments are designed for one diagnosis and emphasize different subdivisions such as symptoms, hearing problems, psychosocial impact, and the need for care. The optimal length of the recall period has not been studied. For these reasons, a new survey is needed that would cover most chronic ear diseases. Methods: A preliminary 24-item survey (EOS-24) was created. Untreated adult patients (included n = 186) with one of seven different chronic otologic conditions from all university hospitals in Finland were recruited to respond to EOS-24 and the 15D general HRQoL instrument. The recruiting otologists evaluated the severity of the disease and the disability caused by it. A control group was recruited. Based on the patients’ responses in different diagnosis groups, the items were reduced according to pre-defined criteria. The resulting survey was validated using a thorough statistical analysis. Results: The relevance and necessity of the original 24 items were thoroughly investigated, leading to the exclusion of 8 items and the modification of 1. The remaining 16 items were well-balanced between subdivisions and were useful in all seven diagnosis groups, thus constituting the final instrument, EOS-16. The most suitable recall period was three months. Conclusions: EOS-16 has been created according to the HRQoL survey guidelines with a versatile nationwide patient population. The survey has been validated and can be used for a wide range of chronic ear diseases as a HRQoL instrument

Spoken language skills in children with bilateral hearing aids or bilateral cochlear implants at the age of three years

Abstract Objectives: Early hearing aid (HA) fitting and cochlear implants (CIs) aim to reduce the effects of hearing loss (HL) on spoken language development. The goals of this study were (1) to examine spoken language skills of children with bilateral HAs and children with bilateral CIs; (2) to compare their language skills to the age-norms of peers with normal hearing (NH); and (3) to investigate factors associated with spoken language outcomes. Design: Spoken language results of 56 Finnish children with HL were obtained from a nationwide prospective multicenter study. Children with HL comprised two groups: children with mild-to-severe HL who used bilateral HAs (BiHA group, n = 28) and children with profound HL who used bilateral CIs (BiCI group, n = 28). Children’s spoken language comprehension, expressive and receptive vocabulary, and phonological skills were compared with normative values of children with NH at the age of three years. Odds ratio (OR) was calculated to compare proportions of children below age-norms in BiHA and BiCI groups. Factors associated with spoken language outcomes were modeled with analysis of covariance. Results: At the age of 3 years, 50%–96% of children with HL performed 1 SD or more below the mean of the normative sample of age-peers with NH in spoken language skills, depending on the language domain. Receptive vocabulary and phonological skills were the most vulnerable language domains. In receptive vocabulary, 82% of the children in the BiHA group and 50% of the children in the BiCI group scored 1 SD or more below the normative mean. The BiHA group was 4.4 times more likely to have poorer receptive vocabulary than the BiCI group. In phonological skills, 96% of children in the BiHA group and 60% of the children in the BiCI group scored 1 SD or more below the normative mean. The BiHA group was 18.0 times more likely to have poorer phonological skills than the BiCI group. The analysis of covariance models showed that unaided pure-tone average, PTA0.5–4 kHz, had a significant effect on spoken language comprehension in the BiHA group. For the BiCI group, age at HL diagnosis and age at CI activation had a significant effect on expressive vocabulary. High maternal level of education had a significant effect on language comprehension and expressive vocabulary and female gender on phonological skills. Conclusions: At the age of 3 years, especially receptive vocabulary and phonological skills caused difficulties for children with HL showing also considerable individual variation. Children with bilateral HAs seemed to be more likely to have poorer receptive vocabulary and phonological skills than children with bilateral CIs. A variety of factors was associated with outcomes in both groups. Close monitoring of spoken language skills of children with HL is important for ensuring similar opportunities for all children with HL and timely intervention, when needed