Interstitial pneumonia and hepatitis caused by minocycline.

A 28-year-old patient is described who presented with progressive dyspnoea and jaundice due to interstitial pneumonia and hepatitis. The most likely cause is a drug-related reaction to minocycline. We discuss the different kinds of drug-related reactions that are most likely involved.

Cerebriform intradermal naevus (a rare form of secondary cutis verticis gyrata).

BACKGROUND: Acquired cerebriform intradermal naevus (CIN) is a rare form of pseudo cutis verticis gyrata. CASE REPORT: A case of acquired CIN of the scalp in a 46-year-old male patient is presented. The clinical and histopathological presentations of CIN are described and the therapeutic possibilities are discussed. CONCLUSIONS: In each individual case the physician must decide whether to do surgery or follow a wait-and-see policy. There is little risk of malignant change of CIN, and surgical excision of such lesions often involves evident mutilation.

Is there a common etiology for the rising incidence of and decreasing survival with adenocarcinoma of the lung?

We studied possible explanations for the deteriorating survival for adenocarcinoma of the lung between 1975 and 1994 in relation with trends in incidence. The proportion of adenocarcinoma among men has been increasing since 1975 and for those born after 1920, while survival has decreased since 1975 and for those born since 1930. Among women, both the proportion of adenocarcinoma and survival have remained more or less constant. The rising incidence and the decreasing survival may both be related to changes in tobacco use, the increased use of low-tar filter cigarettes since the 1960s being the most likely candidate.

Increased but low incidence and poor survival of malignant mesothelioma in the southeastern part of The Netherlands since 1970: a population-based study.

Changes in the incidence and survival rates for malignant mesothelioma in the southeastern part of The Netherlands since 1970 were investigated, using data from the Eindhoven Cancer Registry (ECR). The exposure to asbestos in this area is presumed to be limited. Most of the mesotheliomas occurred in the pleura, where there were 119 (88%) against 15 (11%) in the peritoneum and two in the tunica vaginalis testis. Compared to other European countries, the incidence rate for the southeastern part of The Netherlands was fairly low in the second half of the 1980s. Between 1975 and 1994 the age-adjusted incidence rates (ESR) for pleural mesothelioma increased twofold (from 10 to 19 per one million person-years among men and from 2.4 to 3.8 among women). The rate for peritoneal mesothelioma remained constant. The overall relative 0.5-, 1-, and 3-year survival rates remained 68, 42, and 8%, respectively. The fourfold higher incidence rate for men compared with women reflects the fact that mesothelioma is mainly an occupational disease. In view of presumed limited exposure to asbestos and small geographical variation, the incidence of mesothelioma in the southeastern part of The Netherlands will probably remain low, despite an increase in the past decades.

Improvement and plateau in survival of small-cell lung cancer since 1975: a population-based study.

BACKGROUND: Cytotoxic therapy appears to have improved short-term survival for patients with small-cell lung cancer, but little is known about the results for unselected patients and trends in long-term survival. PATIENTS AND METHODS: One thousand seven hundred ninety-six patients with small-cell lung cancer diagnosed between 1975 and 1994 in southeastern Netherlands. We studied treatment policy for and survival of unselected patients since 1975, when cytotoxic therapy emerged. RESULTS: The proportion patients receiving chemotherapy, with or without irradiation, almost tripled from 30% to 82% for patients younger than 70 years of age and from 15% to 56% for those over 70, whereas the proportion receiving only radiotherapy decreased from 36% to 5% in both age groups. The short-term (< 2 year) survival rate improved markedly between 1975 and 1989, especially for patients younger than 70 (median survival increased from five to 10 months). Two-year survival remained poor (8%). Two percent of all patients younger than 70 years at diagnosis survived for at least eight years, but these patients still represent an excess five-year mortality of 39%. CONCLUSIONS: In southeastern Netherlands short-term survival of patients with small-cell lung cancer improved markedly up to the end of the 1980s, but a major impact on cure rates has not been achieved.

Divergent changes in survival for histological types of non-small-cell lung cancer in the southeastern area of The Netherlands since 1975.

We studied the incidence and survival rates for the histological subtypes of non-small-cell lung cancer, using data from the Eindhoven Cancer Registry over the period 1975-94. The proportions with adenocarcinoma and large-cell undifferentiated carcinoma increased from 11% to 21% and from 11% to 15%, respectively, while those with squamous cell carcinoma decreased from 78% to 62%. The increase in the proportion with adenocarcinoma was only found among men. Although the overall prognosis for patients with non-small-cell lung cancer has remained unchanged, there have been divergent changes between morphological subtypes. Relative 1- and 5-year survival rates for squamous cell carcinoma have improved slightly from 48% to 51% and from 14% to 16%, respectively, because of an increase in the proportion with localized tumours, while relative 1- and 5-year survival rates for adenocarcinoma have decreased from 59% to 45% and from 28% to 18%, respectively, because of a decrease in localized tumours. The proportion with localized tumours and the relative 1-year survival for large-cell undifferentiated carcinoma (about 18% and 30% respectively) were markedly lower. The divergent trends could partly be explained by changes in the histological classification of tumours, but changes in patterns of risk and biological behaviour of adenocarcinoma cannot be excluded.

Endometrial thickness assessed by transvaginal ultrasound insufficiently predicts occurrence of hyperplasia during unopposed oestrogen use.

In the present study, unopposed oestrogens were given to 184 non-hysterectomized women, for a duration varying from four weeks to 24 months, while the endometrial responses were monitored by transvaginal sonography (TVS) and backed up by endometrial sampling (conducted when the endometrial thickness reached 8 mm (double layer) or more, vaginal bleeding occurred during oestrogen administration, or after one year of unopposed oestrogen use). In cases where the endometrial thickness reached 8 mm or more, progestogens were administered for 12 days. In 64% of the women, administration of progestogen could be postponed until at least the fourth month of treatment under the pre-defined decision criteria. Eleven percent of the patients used oestrogens continuously during the two year study period, without any need of additional progestogen. In total, 338 endometrial biopsies were performed; 16 cases of hyperplasia were detected. In three cases, the corresponding endometrial thickness was below 8 mm (in one case, 5 mm). Endometrial thickness could not consistently predict occurrence of hyperplasia. In eight cases, hyperplasia occurred within 4 months of treatment, and in four cases, within only 2 months (of which only one case could possibly be attributed to previous hormone use and none to endogenous oestrogen production). The rapid occurrence of hyperplasia should be taken into account in studies of quarterly progestogen administration with hormone replacement therapy. It is concluded that postponement of progestogen administration with hormone replacement therapy under guidance of TVS only (without biopsies) would not be adequately safe to be recommended for clinical practice.

[Opportunistic lung infections in patients with chronic obstructive lung disease; a side effect of inhalation corticosteroids?]. / Opportunistische longinfecties bij patiënten met chronische obstructieve longziekte; een bijwerking van inhalatiecorticosteroïden?

In four patients, men of 64, 66 and 69 years old and a woman of 65 years, who suffered from chronic obstructive pulmonary disease (COPD) and used inhalation corticosteroids in a relatively high dose (800-1600 micrograms of budesonide per day), a pulmonary infection was diagnosed caused by Mycobacterium malmoense (the first two patients) and Aspergillus (the other two) respectively. Inhalation corticosteroids are of great importance in the treatment of asthmatic patients. Their place in the treatment of patients with COPD is much less clear. The patients did not have an immunological deficiency or anatomical pulmonary or bronchial deformation which could have explained the occurrence of these infections. The high dosages of inhalation corticosteroids may have been involved in the cause of these infections by suppressing the T-cell response locally. In view of this, longterm inhalation corticosteroid treatment should be prescribed in COPD patients only if the efficacy of the medication has been proved in the individual patient involved.

[Adjuvant postoperative radiotherapy in patients with endometrial carcinoma; no effect on length of survival in retrospective study in the Southeastern Netherlands]. / Adjuvante postoperatieve radiotherapie bij patiënten met endometriumcarcinoom; geen effect op overlevingsduur bij retrospectief onderzoek in Zuidoost-Nederland.

OBJECTIVE: To assess the use of postoperative radiotherapy in patients with adenocarcinoma of the endometrium. DESIGN: Retrospective study. SETTING: Catharina Hospital Eindhoven, the Netherlands. METHOD: An assessment was made of referral, survival in relation to patient factors and postoperative radiotherapy treatment, in 422 patients registered in the Eindhoven Cancer Registry between January 1975 and December 1984 with carcinoma of the endometrium. RESULTS: Half the patients (54%) were referred for postoperative radiotherapy, patients over 70 years old less frequently (p = 0.004), patients with deeply infiltrating tumours (p < 0.001) or tumours with poor grade of differentiation (p = 0.03) more frequently. The referral percentages varied between 36% for patients with well differentiated superficial tumours and 83% for patients with poorly differentiated tumours with deep infiltration. Age, postoperative tumour stage and depth of infiltration for patients under 60 showed a statistically significant association with overall survival. A benefit from postoperative radiotherapy with respect to survival could not be established. CONCLUSION: It appears that the variation in referral is also due to differences of opinion concerning appropriate treatment between the referring gynaecologists. This study did not demonstrate a beneficial effect from postoperative radiotherapy. This should be confirmed in a prospective study.

Hereditary spastic dystonia with Leber's hereditary optic neuropathy: neuropathological findings.

Neuropathological findings in a 59-year-old male case of hereditary spastic dystonia with Leber's hereditary optic atrophy included: marked depletion of myelinated nerve fibres in the posterior funiculi, corticopontine tracts and striatum; practically complete neuronal depletion in the putamen and lateral part of the caudate, and mild cell loss in the substantia nigra. The putamina had changed into a spongy fibrillary scar, the pallidal fibres and laminae were practically all degenerated. Moreover, there was generalised mild fibre degeneration of the white matter. The optic nerve showed marked, predominantly central, loss of nerve fibres with demyelination.

Intraobserver and interobserver variability in the quality assessment of cervical smears.

Intraobserver and interobserver variability in assessing the quality of cervical smears, as measured by the presence or absence of endocervical columnar cells and squamous metaplastic cells, was evaluated. In total, 180 cervical smears representing the most important cytologic diagnoses were anonymously rescreened twice by 19 observers with an interval of six months. An absence of endocervical columnar cells was proven to correlate with a high percentage of false-negative diagnoses. Intraobserver agreement on the presence or absence of endocervical columnar cells was 85.7% between the two screenings. A predictive value of 57.7% was found for a negative scoring (absence of these cells) while the predictive value of a positive scoring (presence of endocervical cells) was 87.3%. Of the observer scorings, 83.9% concurred with the final diagnosis; there was no significant correlation between that concurrence and the number of years of experience in cytopathology of the observer. For squamous and squamous metaplastic cells in the cervical smear the predictive value of a negative scoring (absence) was only 20.6%. Compared to the final diagnosis, 69.5% of these scorings matched. A significant and relatively high correlation with the experience of the observer was found for the scoring for the presence of metaplastic cells. Even though the predictive values of these quality scorings were relatively low a significantly higher risk for false diagnoses was established when negative scorings were given. It is therefore advisable to have smears with negative scorings for endocervical columnar cells and squamous metaplastic cells always rescreened by another observer.

Intraobserver and interobserver variability in the diagnosis of epithelial abnormalities in cervical smears.

In a study of variability in the diagnosis of epithelial abnormalities, cervical smears with abnormalities of different severity were rescreened twice by 19 observers with an interval of six months. The observers focused on grading atypicality of squamous, squamous metaplastic and endocervical columnar epithelial cells; their results were compared (1) for the two screenings to assess intraobserver variability and (2) to "review" (final) diagnoses to assess interobserver variability. When the same observer rescreened a smear, 83.3% of the diagnoses did not differ more than one grade between two screenings; however, average intraobserver variability differed considerably for individual observers. The intraobserver variability was only slightly (not significantly) influenced by the years of experience in cytopathology of the observers. Intraobserver variability proved to be an important factor in incorrect diagnoses: 49.1% of the smears with false-negative and 52.9% with false-positive diagnoses at the first rescreening were correctly assessed at the second rescreening. Of all diagnoses made at rescreening, 80.9% were in agreement with the review diagnosis. The interobserver variability also showed considerable differences between observers; however, there was a strong influence of the experience of the observer on the interobserver variability. Atypicality grading of endocervical columnar epithelium by the observers showed a low correlation with the review diagnoses. The relatively low accuracy in the evaluation of this kind of epithelial abnormality is likely to be attributable to the low incidence of abnormal changes of endocervical columnar epithelium. The results of this study point to intraobserver variability as the main cause of false diagnoses. When wrongly diagnosed, severe epithelial abnormalities are more often underestimated than completely overlooked. Apart from training in cytopathology, the establishment of laboratory protocols for multiple screening of even minor abnormalities seem to be the most effective means of reducing the number of false diagnoses.

Effect of population screening for cancer of the uterine cervix in Nijmegen, The Netherlands.

Since the introduction of a population screening program for cervical cancer in 1976, more than 85% of the female population between the ages of 35 and 54 years in the region of the city of Nijmegen, The Netherlands, has been screened. At first screening, severe epithelial abnormalities were diagnosed in 4.4 per 1,000 women, at second screening, in 1.5 per 1,000; and at third screening, in 1.0 per 1,000. The population screening program led to a marked increase in the detected number of carcinomata in situ. The number of cases of squamous cell cancer diagnosed in the first screening period did not increase. Once the population was screened, the detection rate of invasive squamous cell cancer in the group of women ages 35 through 54 decreased from 18.6 per 10(5) during the period prior to the screening to 9.0 per 10(5) after the first screening and 3.3 per 10(5) after the second screening. For the women above age 54, the incidence of invasive cancer was reduced by 58% after the second screening. The number of invasive cancers diagnosed in women under age 35 remained relatively small in spite of the large number of cases of carcinoma in situ.