A primary healthcare-based intervention to improve a Danish cervical cancer screening programme: a cluster randomised controlled trial.

BACKGROUND: The proportion of non-attenders in cervical cancer screening is high, and should be minimised. A targeted invitation to women not participating for the last 5 years in cervical screening was evaluated to determine whether it would decrease the number of these women. Increasing general practitioners' attention to the screening programme for cervical cancer was also evaluated to determine whether it would increase participation. METHODS: A cluster randomised controlled trial conducted in the county of Aarhus, Denmark. All women registered with a GP were randomised. Regardless of group allocation, all women received a normal invitation. In the intervention arm, GPs were visited to facilitate quality enhancements of the screening programme, combined with a special targeted invitation to women aged 23-59 registered with the GP but not attending screening for the last 5 years. The main outcome was the proportion of non-attenders and the secondary outcome was coverage rate. RESULTS: 117 129 women registered with 190 GPs were included in the study. 1737 non-attenders had a Papanicolaou smear during follow-up. The decline in non-attenders was 0.87% (95% CI 0.57% to 1.16%) after 9 months in favour of the intervention. A difference of 0.94% (95% CI 0.21% to 1.67%) in the change of coverage rate was observed at 6 months, which increased to 1.97% (95% CI 0.03% to 3.91%) at 9 months in favour of the intervention. CONCLUSION: It is possible to decrease the proportion of non-attenders and increase the coverage rate in a screening programme for cervical cancer using a special targeted invitation to non-attenders combined with a visit to GPs. To further improve participation, other barriers must be identified and addressed.

Screening history of women with cervical cancer: a 6-year study in Aarhus, Denmark.

To identify possible weaknesses in cervical screening in Aarhus County, 10 years after the programme was introduced, screening histories were examined. A major problem for the screening programme was that 31% of women were never screened and 61% under-screened, the latter group being significantly dominated by older women and high-stage tumours.

[Comparison of monolayer specimens and conventional smears]. / Sammenligning af monolagsprøver og konventionelle "smears".

INTRODUCTION: Monolayer specimens were compared with conventional smears in a split sample study. The quality of the specimens, sensitivity, time consumption, and costs were elucidated. METHOD: Conventional smears and fixated residual material from 1701 women were available. RESULTS: The number of inadequate/less adequate specimens was reduced significantly (p < 0.001). Diagnostic agreement was found in 1531 (90%) of the 1701 cases (kappa = 0.52, SE (kappa) = 0.026). Dysplasia (NOS) was diagnosed in seven monolayer specimens (0.4%) versus 33 smears (1.9%) and ratio atypia/low grade was reduced by 33%, which indicates greater accuracy in diagnosis in monolayers. Histological follow-up showed sensitivities of 95% (monolayers) and 94% (smears). The time consumed (laboratory work, screening) on a smear versus a monolayer specimen was 11.5 minutes versus 9.3 minutes. Utensil costs of a smear are kr. 10.69. compared to kr. 26.50 for a monolayer specimen. CONCLUSION: The higher costs should be set against the saving in significantly improved specimen quality, improved diagnostic accuracy, and shorter time consumption. The use of the monolayer technique (direct to vial) is recommended to replace the conventional smear.

[Partial re-screening of all negative smears. A method of quality control of pathology department concerning smear screening against cervix cancer]. / Partiel rescreening af alle negative "smears". En metode til patologiafdelingens kvalitetskontrol af "smear"-screening mod livmoderhalskraeft.

Partial rescreening of all negative smears is recommended as the most cost-effective method of internal quality control. The method was tested by eight cytotechnologists and the average diagnostic sensitivity, assessed upon their answering of 200 test-smears (150 negative and 50 positive) was 80%, while specificity vas calculated to 95%. Partial rescreening has here-upon been used in daily routine. After one year 21,000 smears have been re-screened. Twenty-nine cases of false negatives, 16 with atypia, eight with koilocytosis, and five cases with dysplasia have been detected, which corresponds to an overall false negative rate on 3%. In five of the 29 false negative cases with dysplasia histological follow-up has shown three cases of CIN III (two carcinoma in situ, one severe dysplasia), one case with CIN II (moderate dysplasia) and one case with CIN I (mild dysplasia). Conclusively, partial rescreening of all negative smears implies an improved quality with reduction of the number of false negative specimens.

[Bladder tumor antigen test versus urinary cytology in patients with bladder tumors]. / Undersøgelse for blaeretumorantigen versus urincytologi hos blaeretumorpatienter.

The value of the BARD bladder tumour antigen (BTA) test for the diagnosis of bladder tumour was compared to urinary cytology. A total of 60 patients with bladder tumours (Category Ta: 39 patients and Category T1-4: 21 patients) were investigated. Urinary cytology was found to be more sensitive than the BTA test. The overall sensitivity of cytology was 0.63 compared to 0.27 for the BTA test. The sensitivity of both tests improved with increasing tumour severity. For Ta tumours and T1-4 tumours the sensitivity of cytology was 0.46 and 0.95 respectively, and for the BTA test it was 0.13 and 0.53 respectively. We conclude that urinary cytology is superior to the BTA test. The BTA test cannot be recommended either for bladder tumour screening or monitoring for recurrence because of too many false negative results. Because of its high specificity (0.93), a positive BTA test might reduce the number of flexible cystoscopies, and prepare the patient directly for tumour resection.

Cytobrush and endocervical curettage in the diagnosis of dysplasia and malignancy of the uterine cervix.

BACKGROUND: The validity of cytobrush and endocervical curettage combined with colposcopically directed biopsies in the diagnosis of cervical dysplasia and malignancy has not been evaluated in randomized trials. We aimed to elucidate the diagnostic validity of the two methods. METHODS: A prospective, randomized study of 180 consecutive patients. All patients were examined without anesthesia by colposcopically directed biopsies of the ectocervix and randomly assigned to either cytobrush or endocervical curettage. Patients with < or = CIN 1 were investigated with the alternative method three months later. Patients with > or = CIN 2 had a cone biopsy. RESULTS: One hundred and thirty-one patients were evaluable. The sensitivity of cytobrush and endocervical curettage combined with colposcopically directed biopsies of the ectocervix was 96% and 84% (p = 0.08), respectively. The specificities of the two investigations were 95% and 88%, respectively (p = 0.78). All cytobrush specimens were evaluable but because of a low recovery of endocervical material a diagnosis could not be made in 12% of the patients examined by endocervical curettage. CONCLUSION: The sensitivity of the combined use of cytobrush and biopsies of the ectocervix was equal to or higher than the sensitivity of endocervical curettage and ectocervical biopsies. The specificities of the two investigations were much alike. All cytobrush specimens were evaluable but a diagnosis could not be performed in 12% of the endocervical curettage specimens because of too little endocervical material. Furthermore, cytobrush is less inconvenient to the patient. Therefore, in the follow-up of patients with cervical dysplasia endocervical curettage may be replaced with cytobrush.

Significance of variations in section mounting technique for nuclear stereology and morphology in urinary bladder neoplasms.

Owing to its toxicity it would be desirable to avoid xylene in the processing of histological tissue. Consequently, modifications of the section mounting technique excluding xylene have recently been suggested. Changes in tissue preparation might, however, influence histopathological structures used for malignancy grading of tumours. In the current study, we investigated the impact of alterations in the mounting process on the subjectively evaluated quality of nuclear morphology and on the stereologically obtained mean nuclear volume, vv(nuc), of urothelial neoplasms. Paraffin sections from 14 tumours were, after the haematoxylin-eosin staining, mounted with DPX and a coverslip either, 1) from the water bath, 2) after dehydration in ethanol but without clearing, or, 3) after dehydration and xylene clearing. We found that the nuclear morphology of ethanol-treated and xylene-cleared specimens was somewhat more brilliant than that of sections mounted from water. The vv(nuc) of xylene-cleared sections ranged from 142 to 751 microns3, and the mean value of 350 microns3 was not significantly different from that of ethanol-treated sections of 367 microns3 (2p = 0.67). In contrast, the mean vv(nuc) of sections mounted from water was 459 microns3, approximately 30% larger (2p < or = 0.02). Thus, although previous studies have demonstrated the prognostic value of vv(nuc) in patients with bladder cancer, the present study shows that modifications in section mounting technique may significantly influence the results, underscoring the need for standardization of tissue processing. Sections mounted from ethanol seem to be as good as routine xylene-cleared sections, whereas sections mounted from water have a less brilliant morphology and results of nuclear stereology different from those of routine sections.

Body growth in relation to tonsillar enlargement and tonsillectomy.

Severe airway obstruction caused by tonsillar enlargement can result in disturbances in body growth. The effect of this interference and of tonsillectomy in the child with only moderate symptoms have been less satisfactoril evaluated. In this study, 122 children with symptoms and signs of tonsillar obstruction were investigated concerning the height and weight before and after tonsillectomy. None of the individuals demonstrated cardiopulmonary complications of tonsillar obstruction. Altogether 10% of the children exhibited abnormalities in body weight and/or length prior to surgery. Especially during the first postoperative year, the weight and height gain exceeded the expected in 75% of the patients. The accelerated weight gain increased with tonsil size, but there was no relation to the extent of difficulties in swallowing or sleeping disruptions. The results support the hypothesis that tonsillar hypertrophy frequently is associated with disturbances in body growth and that this is seldom demonstrable prior to tonsillectomy.

The influence of tonsillar obstruction and tonsillectomy on facial growth and dental arch morphology.

Children, who were tonsillectomized because of sleep apnea were examined with respect to facial growth and dental arch morphology. Dental casts and lateral roentgencephalograms were analysed before surgery and two years after tonsillectomy. The findings were compared to data from children without tonsillary obstruction. A higher proportion of malocclusion than normal, especially open bite and crossbite, was noticed before surgery. Two years after surgery, 77% of the open bites were normalised and 50-65% of the buccal and anterior crossbites. The best results were seen in children operated before the age of 6.

Down syndrome and sleep apnea--a therapeutic challenge.

This case report describes 3 patients with Down syndrome and obstructive breathing problems, ages: 5 months, 15 months, and 22 years. The youngest one had normal cardiopulmonary function at birth, but soon developed a pulmonary hypertension. The next had a severe atrioventricular defect and additional pulmonary hypertension and there was little hope for her to survive heart surgery. The oldest one had had apneas since childhood with increasing severity, but was regarded as having normal heart function. All 3 were operated to relieve their breathing obstruction. The 5-month-old boy improved only slightly after an initial UPPP and had to be tracheotomized, which solved his problems. The tracheotomy could be removed when he was one year. The 15-month-old girl was cured of her breathing problems through an A + T and survived her heart surgery one month later. Tonsillectomy and UPPP was performed on the oldest patient. Following surgery, he had an episode of life-threatening bleeding and developed a DIC syndrome, and was critically ill for 18 days. After he recovered, his sleep apnea had improved. Once a myxoedema was diagnosed and treated, he made further progress. These cases stress the significance of early recognition of sleep apnea in children with Down syndrome and the importance of a careful preoperative investigation in collaboration with cardiologists.

The effect of Xylometazoline on the mucosa of human maxillary sinus.

A stuffy and running nose are two of the most expressed symptoms of acute rhinosinusitis and have made the use of decongestants very common. The medication, oral or nasal, gives relief from symptoms but its effect on the healing of the infection, positive or negative, is not clear. The effect of Xylometazoline on the blood flow, the pulse amplitude and the gas exchange in the antral mucosa of the maxillary sinus was studied in five healthy subjects. Our experiments show that the mucosal pulse amplitude and the blood flow are strongly reduced by insufflation of Xylometazoline but the gas exchange in the mucosa is only lowered to a minor extent. The reduction in gas exchange is not great enough to allow the gas mixture to be altered. The defence mechanisms in the antral mucosal lining, i.e. the mucociliary-, the immuno- and the phagocytotic mechanisms are all dependent on the blood flow and the gas exchange through narrow maxillary ostia of the pumping effect generated by the mucosal pulse wave. The reduction in blood flow and pulse amplitude in the maxillary mucosa caused by Xylometazoline leads us to consider that, although not harmful then it is at least not helpful, in healing rhinosinusitis. Since oral decongestants have almost the same effect on the mucosa as nasal decongestants, we do not think that any of the medicines faciliate the healing of infections in the upper airways even if they make the patient feel better during the infection.

Blood flow and pulse amplitude in the mucosa of the human maxillary sinus in relation to body posture.

The paranasal sinuses are non-collapsible ventilated gas pockets without any known function. They should, however, be adequately ventilated to stay healthy. Persons lying in a recumbent body position compared to persons sitting or standing upright have reduced antral mucosal blood flow, a reduction of 35%, and a congested mucosa which reduces both the mucosal gas exchange and the perostial ventilation, creating a more anaerobic antral gas mixture facilitating pathogenic bacterial growth and reduced ciliary activity. It is, therefore, recommendable for patients with sinusitis to treat themselves or be treated in an upright or semi-recumbent body position.

Observer reproducibility in grading dysplasia in colorectal adenomas: comparison between two different grading systems.

The two most well known and well defined grading systems for dysplasia in colorectal adenomas were compared with regard to reproducibility. The Konishi-Morson system (KMS) operates with several histological and cytological variables and grades of mild, moderate, and severe dysplasia. The Kozuka system is based on the extent of nuclear pseudostratification and also has three grades of dysplasia (III-V). As the group of severe dysplasia is very large in this system, it was extended with two higher grades, similarly based on individual histological criteria, known hereafter as the extended Kozuka system (EKS). Fifty six adenomas were graded by two observers, each observer grading twice according to the KMS criteria and twice according to EKS criteria. Intraobserver reproducibility was excellent for the KMS and moderate for the EKS, but this was not significant. The overall interobserver reproducibility was similar (moderate) for the KMS and for the EKS. Kappa values for interobserver reproducibility on individual categories were excellent for severe dysplasia according to the KMS, but low for all other categories in both systems. By simplifying both systems into two groups a high reproducibility can be obtained, but this implies that all the original grades (III-V) for the EKS must be grouped together. It is therefore recommended that a simplified KMS is used for further studies on the biological importance of dysplasia and for comparison between histological changes and other markers for colorectal neoplasia.

Histological evaluation of prostatic cancer. (III): Reproducibility of assessment of tumour volume and its possible significance for prognosis.

The aim of this study was to evaluate the INTER- and INTRA-observer reproducibility of prostatic cancer volume defined as the percentage of chips with carcinoma in transurethrally resected tissue. All histological slides from 80 consecutive cases of prostatic cancer were blindly evaluated on two independent occasions by each of four pathologists. The correlation was expressed by Spearman's rank correlation coefficient (R). Both the overall INTER- and mean INTRA-observer correlation of tumour volume were high with R being respectively 0.905 and 0.918. With reference to stage A1 and A2, data were transformed to an ordinal scale with 2 categories (less than = 5%, greater than 5%). The overall INTER- and mean INTRA-observer agreement of this classification were 0.926 and 0.943 respectively--the corresponding kappa coefficients being 0.68 and 0.74. It is concluded that in transurethrally resected tissue a highly reproducible index of the resected prostatic cancer volume can be given by the percentage of chips with tumour. The prognostic significance of this parameter is discussed.

Histological evaluation of prostatic cancer. (II): Reproducibility of a histological grading system.

The aim of this study was to evaluate the reproducibility, expressed by kappa coefficients, of the histological grading system of prostatic cancer as proposed by Schroeder, Hop, Blom and Mostofi in 1985. This grading system has five prognostic groups based on combinations of growth pattern, mitoses and nuclear anaplasia. All histological slides from 85 cases of prostatic carcinoma were blindly evaluated on two independent occasions by each of four pathologists. The overall INTER-observer agreement and mean INTRA-observer agreement regarding "prognostic group" were 0.55 and 0.69 respectively, whereas the kappa coefficients were 0.38 and 0.57 respectively. An acceptable level of INTER-observer reproducibility of prognostic group I (kappa = 0.70), of the parameter "growth pattern" (kappa = 0.60) and of "slight nuclear anaplasia" (kappa = 0.62) was found. A low overall kappa coefficient of "mitoses" and "nuclear anaplasia" was found. Based on the well reproducible parameters a simplified grading system is proposed.

The effect of physical work on the mucosal blood flow and gas exchange in the human maxillary sinus.

The paranasal sinuses are lined with respiratory mucosa of principally the same structure as in the nasal mucosa but somewhat thinner. This mucosa has a rich blood flow and advanced system of blood vessels regulated mostly by the autonomous nervous system but also by other factors as acid/base balance and endocrine activity. The thickness of the nasal mucosa regulates the nasal breathing resistance and varies with among other factors, body activity. In this investigation we have studied the effect of physical work on the human maxillary sinus mucosa. The investigation shows that, as in the nose, the blood flow and the pulse amplitude are considerably reduced during physical work, in situations of heavy work falling to about half of the normal level, and probably result in the redistribution of blood from the respiratory mucosa. The gas exchange in the paranasal sinus is reduced only to a small extent, the reduction being too small to change the antral gas composition towards pathological conditions.

The relationship between body posture and pressure in occluded maxillary sinus of man.

One of the most common symptoms in sinusitis is pain over the infected cavity increasing when the patient is bending forward or lying down. It is commonly thought that this increase in pain is a result of increased pressure in the paranasal cavities when bending forward. In this investigation we have found that changing the body position from sitting to recumbent or even to "head between knees" gives a manometrical pressure rise in the sinus that is too small to cause a pressure-mediated pain. The pain is probably caused by a dilation in the blood vessels of the infected mucosa when the patient is bending forward or lying down.

Reproducibility of histomorphologic diagnoses with special reference to the kappa statistic.

Systems for classification and grading used in pathology should ideally be biologically meaningful and at least be reproducible from one pathologist to another. A statistical method to evaluate reproducibility (non-chance agreement) for several observers using nominal or ordinal categories has been developed and refined over the past few decades--the kappa statistic. A high level of observed agreement among different pathologists can either signify a high level of reproducibility, if agreement by chance is low, or express a low level of reproducibility, if agreement by chance is almost as high as the observed agreement. Therefore, the observed agreement says nothing in itself, unless it is low. The kappa value, however, indicates how much better the observers are compared to a throw of the dice, and therefore gives the real credit to the agreement which was found. We have developed a user-friendly computer program for calculating inter- and intra-observer agreement of 2 or more observers. By calculating associations between different categories and different observers, the statistic furthermore obtains a function close to the parameter of accuracy. We recommend the use of the above method before a set of nominal or rank scale parameters are used for deciding prognosis and treatment of patients. By submitting a diskette the computer program will be available at no cost.