Individual and work-unit measures of psychological demands and decision latitude and the use of antihypertensive medication.

PURPOSE: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication. METHODS: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish National Prescription Registry. Odds ratios (OR) comparing the highest and lowest third of the population at individual and work-unit level, respectively, were estimated by multilevel logistic regression adjusted for confounders. Psychological demands and decision latitude were tested for interaction. Supplementary analyses of 21 months follow-up were conducted. RESULTS: Among women, increasing psychological demands at individual (adjusted OR 1.54; 95 % CI 1.02-2.33) and work-unit level (adjusted OR 1.41; 95 % CI 1.04-1.90) was significantly associated with purchase of antihypertensive medication. No significant association was found for decision latitude. Follow-up results supported an association with psychological demands but they were not significant. All results for men showed no association. Psychological demands and decision latitude did not interact. CONCLUSION: High psychological work demands were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job strain model.

Delayed dental maturity in dentitions with agenesis of mandibular second premolars.

OBJECTIVES: To evaluate dental maturity in the mandibular canine/premolar and molar innervation fields in children with agenesis of the 2nd mandibular premolar and to associate these findings with normal control material. SETTING AND SAMPLE POPULATION: Department of Orthodontics, Institute of Odontology, University of Copenhagen. Eighty-three panoramic radiographs (27 girls and 31 boys with agenesis of one mandibular 2nd premolar and 17 girls and eight boys with agenesis of both mandibular 2nd premolars) represented all mandibular second premolar agenesis cases from a material of 2847 radiographs. MATERIAL AND METHODS: On each radiograph, dental maturity of all available mandibular premolars, canines and 2nd molars was evaluated and categorized in maturity stages according to Haavikko whose material served as control material. Descriptive statistics given by sample mean, standard deviation and range for each tooth stratified by gender and agenesis. Ninety-five percentage confidence limits and T-statistics were used. p-values <5% were considered significant. RESULTS: In unilateral agenesis, the canines are specifically delayed in both girls and boys, with a larger delay in girls (p=0.009). The second molar is not delayed in boys (p=0.98) but is in girls (p=0.04). The differences in delay for the canine compared to the second molar are significant for both girls and boys. The results show a considerable delay in tooth maturation within the canine/premolar innervation field predominantly in girls. The 2nd molar is delayed in girls but not in boys.

Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group.

No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two independent strata and received a total of 141 cycles (median 2). Median age was 61 years, range 25-76. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively. Non-haematological toxicity consisted mainly of grade 2/3 dyspnoea in 36% of patients and grade 2/3 fatigue in 28%. One treatment-related toxic death due to septic shock was reported. Best overall response was no change with 60% in the leiomyosarcoma group and 53% in the non-leiomysarcoma group, respectively. The 3 months progression-free survival estimates are 56% for leiomysarcomas and 26% for other histologies, respectively. Using a two-step statistical design, the trial was stopped after the first step in both strata, due to lack of activity. In pretreated soft tissue sarcoma patients, Exatecan is well tolerated but does not achieve any objective responses. However, with respect to progression-free survival, Exatecan did show some activity in leiomyosarcomas.

Phase 1 European Organisation for Research and Treatment of Cancer study determining safety of pegylated liposomal doxorubicin (Caelyx) in combination with ifosfamide in previously untreated adult patients with advanced or metastatic soft tissue sarcomas.

This phase I study evaluated the toxicity of first-line combined pegylated liposomal doxorubicin (Caelyx) and ifosfamide in patients with advanced and/or metastatic soft tissue sarcomas. Five dose levels (L) were studied: Caelyx 30 mg/m2 (L1-4) or 40 mg/m2 (L5) 1-h infusion d 1 q 3 weeks + ifosfamide and mesna at X g/m2/4 h d 1-3 q 3 weeks at five doses: L1: X = 1.7 g; L2: X = 2 g; L3: X = 2.5 g; L4 and L5: X = 3 g. Cohorts of 3 patients were entered at each level unless a dose-limiting toxicity (DLT) occurred. In case of DLT in 1 of 3 patients a new cohort was added. Toxicity was evaluated by Common Toxicity Criteria (CTC). A total of 28 patients was included: 4 at dose L1, 8 at L2, 3 at L3, 6 at L4, and 7 at L5. Median age was 60 years (range 29-69 years). Male/female ratio was 12/16. Seventy-five percent of patients had a performance status of 1.0 and 36% had leiomyosarcomas. No DLT was observed at dose L1-4. Six patients developed a DLT at dose L5, and thus the recommended dose is level 4 (i.e. Caelyx 30 mg/m2/1 h d 1+ifosfamide at 3 g/m2/4 h d 1-3 q 3 weeks). Few haematological and biochemical events were observed and the principal toxicities were granulocytopaenia and leucopaenia. Five patients discontinued therapy because of toxicity, 4 of them at dose level 5. Non-haematological toxicities > grade 2 were also few. Palmar-plantar erythrodysesthesia (PPE) > grade 1 was not seen. Two patients obtained partial response (PR) and 13 stable disease (SD). Median overall survival (OS) was 333 d and median progression-free survival (PFS) 174 d. In conclusion, this seems to be a feasible combination in patients with advanced soft tissue sarcomas, allowing ifosfamide to be given in a dosage similar to that used when given alone. The recommended dose for future studies is Caelyx 30 mg/m2/1 h d 1+ifosfamide 3 g/m2/4 h d 1-3 q 3 weeks.

Sinonasal schwannoma--a clinicopathological analysis of five rare cases.

Schwannoma of the nasal cavity or the sinuses is a rare condition. We report a small series of five consecutive patients; three males and two females, age range 22-81 years, all Caucasian. Symptoms were typically non-specific, and the tumours were often quite large when diagnosed, being locally infiltrating and even destructive. Histologically, the tumours were remarkable by sparse occurrence of Antoni type B areas and lack of encapsulation. Four cases were benign; however, one case of melanotic schwannoma, exhibited malignant transformation. Two of the patients had intracranial involvement, but with an intact dura. All tumours were treated surgically; only the malignant case received adjuvant radiotherapy. Patients were followed from five months to 15 years, with a median of 57 months. The benign cases have so far shown good prognosis without recurrences; however, in the case of the melanotic schwannoma a fatal malignant transformation was seen 13 years after initial diagnosis. On the basis of our review early detection and complete surgical removal is recommended.

Current soft-tissue sarcoma classifications.

In order to analyse the impact of modern sarcoma classification criteria, pathological material from 281 extremity soft-tissue sarcomas (STS) was reviewed. The cases were originally diagnosed between 1972 and 1994, and the most frequent diagnoses then were malignant fibrous histiocytoma (MFH) (26%), liposarcoma (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the proportions had changed significantly, with the largest group now being leiomyosarcomas (20%), liposarcomas (17%), synovial sarcomas (14%), and sarcomas "not otherwise specified" (NOS) (11%). The original diagnosis was changed in 57% of the cases; in particular, the number of fibrosarcomas was reduced from 32 to 6, and MFHs from 72 to 2, with 22 renamed as myxofibrosarcomas; 20 (7%) were found not to be sarcomas. The main reasons for these results are the recent advances in immunohistochemistry (IHC) together with changes in nomenclature. The findings have obvious implications, in particular for retrospective research.

Histopathological grade and response to chemotherapy in advanced soft tissue sarcomas.

In a retrospective analysis, we evaluated the possible significance of histopathological grade with regard to response to chemotherapy in advanced soft tissue sarcomas. In three EORTC protocols, the same dose-schedule was used for patients randomised to treatment with doxorubicin as a single agent (75 mg/m2 every third week). The submitted pathological slides from 94 of these patients were reviewed and graded. The following parameters were subjectively graded (+/++/+ + +): nuclear pleomorphism, necrosis, cellularity and vascularity. Mitoses were counted in 20 high-power fields, and a final grade assigned as I, II, IIIA or IIIB. The results were tested both with regard to response (complete response + partial response vs. no change + progressive disease) and survival. However, no statistically significant correlations or trends could be demonstrated. Thus, tumour grade, although a prognostic factor by itself, does not seem to be able to predict response to chemotherapy in the advanced stage.

Adenocarcinoma of the cervix and adenocarcinoma of the endometrium: distinction with PCR-mediated detection of HPV DNA.

The differential diagnosis between primary endocervical adenocarcinoma and adenocarcinoma originating in the endometrium may in some cases be difficult. The two cancer types have a different genesis, with human papillomavirus (HPV) as an important causal factor in the development of primary cervical carcinoma. In this study, the paraffin-embedded cervical tissues from 23 patients with stage II endometrial carcinoma and from 50 patients with primary cervical adenocarcinoma were examined for HPV DNA of types 16, 18, and 33. HPV DNA was demonstrated in 70% of the primary endocervical adenocarcinomas and in none of the endometrial carcinomas. It is concluded that HPV detection may be useful in the differential diagnosis of some cases of cervical and endometrial adenocarcinoma.

Glomus tumours. An immunohistochemical study.

The histological and immunohistochemical features of 20 glomus tumours (glomangiomas) were studied retrospectively in routinely processed material. The tumours came from 18 patients (9 women and 9 men, aged 25 to 80 years); two were recurring lesions. Twelve were classified as solid glomus tumours, eight as glomangiomas. Small nerve fibres were present in all except one. A variable number of mast cells were found in the stroma. The glomus tumour cells were negative when stained for Neuron-Specific Enolase, Glial Fibrillic Acidic Protein, S-100 Protein, Chromogranin, or with the Ulex Europaeus Lectin type 1. Conversely, all were found to be positive for Actin, Myosin, and Vimentin. Four exhibited an equivocal reaction for Desmin, the rest were negative. This immunohistochemical profile is in accordance with the findings of other investigators and can be helpful in differential diagnosis. It also shows the glomus cell to be related to smooth muscle cells and pericytes. The majority of these lesions are probably hamartomas, but a few may be true neoplasms.

Cytokeratin intermediate filament pattern in uterine cervical biopsies.

Twenty-seven uterine cervical biopsies with histological diagnoses ranging from normal through dysplasia to invasive carcinoma were analysed for cytokeratin pattern in two-dimensional gel electrophoresis. No direct correlation between histological diagnosis and cytokeratin pattern was observed.

Filter in situ hybridisation: an evaluation of the FISH technique for HPV detection in cervical swabs.

The filter in situ hybridisation (FISH) method for detection of HPV in cervical swabs was evaluated against the Southern blot technique on concomitant cervical biopsies. Of 73 biopsies, HPV 16 DNA sequences were found in 26 biopsies and HPV 18 sequences in 2 biopsies. Analysis by FISH of the corresponding smears detected 58 and 100% of these, respectively. Of the smears corresponding to the HPV-negative biopsies, 17% were HPV 16-positive and 3% were HPV-18 positive by FISH. Re-hybridisation with cold plasmid added for competition did not change these results. To estimate the risk of spurious hybridisation between vector remnants in the probe and bacterial DNA sequences present in smears, we have hybridised by FISH to preparations of the 19 most common vaginal microorganisms. Of these, E. coli, which is present in about 10% of cervical smears, hybridised strongly with a probe of the plasmid vector pBR322 and may be a significant cause of false positive FISH results. None of the bacteria hybridised with probes of purified HPV when cold, denatured plasmid was added for competition. Analysis by FISH with probes of purified pBR322 to 167 smears of a patient control group resulted in 6% positive reactions. In hybridisations with probes of HPV 16 and 18 to 2 or 3 different filter preparations of the same smear, identical results were obtained in 18 of 19 smears, indicating a good reproducibility by the FISH method. The high percentage of HPV negative smears is equivalent to the rates known from cytology and may reflect sampling errors.

Ectopic meningioma of a finger. Case report.

A case of an ectopic meningioma in a 67-year-old woman is presented. The tumor was located subcutaneously on the little finger of her right hand. Microscopic examination revealed a typical psammomatous meningioma with no signs of malignancy. The location of this tumor is most unusual, and theories regarding its histogenesis are briefly discussed. A neuroectodermal origin is suggested.

Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction.

Most nasopharyngeal carcinomas (NPCs) are of the nonkeratinizing or undifferentiated types, which are consistently associated with Epstein-Barr virus (EBV). The smaller group of highly differentiated, keratinizing NPCs seems to be only infrequently associated with EBV. In order to examine whether these rare tumors were related to another oncogenic virus, the authors used the polymerase chain reaction to examine paraffin-embedded sections of 15 keratinizing NPCs for human papillomavirus (HPV) types 6, 11, 16, and 18 genomic sequences. HPV DNA was found in 4 tumors (1 HPV-11-positive, and 3 HPV-16-positive tumors). None of 23 undifferentiated or nonkeratinizing NPCs harbored HPV DNA. The putatively oncogenic HPV type 16 may thus be involved in the carcinogenesis of some EBV-negative keratinizing squamous cell nasopharyngeal carcinomas.

Imaging of chondrosarcoma with histopathological and prognostic correlation. An analysis of 49 cases mainly based on plain film radiography.

PURPOSE: To investigate the course of chondrosarcoma in relation to radiographic and histopathologic findings. MATERIAL AND METHODS: 49 consecutive patients seen during an 11-year-period were analysed, including re-evaluation of their radiographic and histopathologic material. RESULTS: Forty-two patients had radiographic changes typical for cartilaginous tumours, in 37 with malignant stigmata. Seven patients had malignant changes not typical for chondrosarcoma. By histopathologic grading 16 patients had grade I, 17 grade II and 16 grade III tumours. Six of the grade II-III tumours were histopathologic variants (mesenchymal, dedifferentiated or myxoid chondrosarcomas). Surgical removal of the tumour was performed in 42 patients, 41 of whom were followed up for 0.4-11.4 years (median 3.8 years). Local recurrence occurred in 7 patients, and 11 patients developed metastases. Ten patients, 4 with local recurrence and metastases, and 6 with metastases only were dead at the end of the follow-up. The actuarial 5-year overall survival rate was 64%. The occurrence of local recurrence, metastases and death was found to be related to the histopathologic grades II and III. Atypical radiographic features only occurred in grade II-III tumours and were related to metastases and death, but not to local recurrence. CONCLUSION: Atypical radiographic findings were related to high-grade malignancy and poor prognosis.

Detection of human papillomavirus type 16 DNA sequences in archival cervical tissues by the polymerase chain reaction.

We have evaluated the polymerase chain reaction for the detection of viral DNA sequences in paraffin-embedded archival tissues. In 63 frozen cervical biopsy specimens that were taken from premalignant and invasive lesions, Southern blotting detected human papillomavirus (HPV) type 16 DNA in 28 (44%) of the samples. In the polymerase chain reaction analysis of the formalin-fixed, paraffin-embedded mirror biopsy specimens, 46 (73%) of the tissues were found to be positive for HPV type 16. In three Southern blotting-positive cases, the DNA of the paraffin-embedded sections was too scant or too degraded to allow the detection of HPV DNA by the polymerase chain reaction. In 21 Southern blotting-negative cases, HPV type 16 DNA could be demonstrated in the archival sections by the polymerase chain reaction technique--a sensitivity improvement of more than 80% over the standard method of HPV detection in tissues.

Intramuscular lipoma of the lower limb. Long-term follow-up after local resection.

We report 12 patients with infiltrating muscular lipomas of the lower limbs all treated by wide resection. During follow-up averaging seven years, the tumour recurred in five patients. Our results and those reported by others suggest that, in order to avoid recurrence, this tumour, although benign, should be treated by total excision of the muscle or by compartmental resection. Hormonal imbalance was suspected in 9 of the patients but an oestrogen receptor analysis of the histological samples proved negative.

HPV 11, 16 and 18 DNA sequences in cervical swabs from women with cervical dysplasia: prevalence and associated risk of progression.

Cervical swabs obtained from 164 women with histologically proven preinvasive and invasive cervical neoplasia were analysed for HPV type 11, 16 and 18 DNA by filter in situ hybridisation. HPV 16 or 18 was detected in 8 of 24 swabs from patients with invasive squamous cell carcinoma (33%), in 59 of 100 patients with carcinoma in situ or severe dysplasia (59%) and in 16 of 40 patients with mild or moderate dysplasia (40%). HPV 6 or 11 was found in only 2% of all swabs. Thirty-eight of the patients participated in a prospective follow-up study and were monitored non-invasively by cytology and colposcopy for 8 to 36 months. 25 patients had persisting or progressive lesions, 13 of which harboured HPV 16 or 18. Of 13 patients who had complete resolution of the dysplasia, only 2 were HPV-positive. The study indicates a significantly higher risk of malignant progression when the cervical dysplasia is associated with HPV 16 or 18 infection.

Hormonal factors and prognosis in epithelial ovarian cancer: a multivariate analysis.

When a significantly lower follicle stimulating hormone (FSH) level was found in patients with epithelial ovarian carcinoma, it was decided to analyze the influence of hormonal factors on prognosis. Thirteen factors were tested for prognostic significance in 35 women with epithelial ovarian carcinoma. Age, FIGO-stage, histopathological grade, residual tumor, treatment, gonadotrophins and steroid hormones were tested. By univariate log-rank testing a significantly shorter survival time was found for patients with ascending FIGO-stage, residual tumor mass, estradiol < 0.10 nmol/l, progesterone < 2.0 nmol/l and DHEAS < 1300 nmol/l. In the Cox model the independently significant prognostic factors found were residual tumor mass (P < 0.001) with a risk estimate of 2.65, progesterone (P < 0.05) with a risk estimate of 0.29 for a progesterone level > 2.0 nmol/l and total testosterone (P < 0.03) with a risk estimate of 0.29 for a total testosterone level > 1.15 nmol/l. The present findings, together with the assumption that an elevated gonadotrophin level may induce ovarian tumor growth (the gonadotrophin theory), earlier findings of estrogen and progesterone receptors in human ovarian cancer, and the in vitro demonstration of gonadotrophin-growth-stimulation of human malignant epithelial tumors, justify a thorough investigation of the interaction between steroid hormones and receptors, gonadotrophins, tumor bulk and survival in future research protocols.

Liposarcoma metastatic to the orbit.

PURPOSE: To describe a patient with liposarcoma metastatic to the left orbit. METHODS: A 72-year-old man was admitted with diplopia and proptosis of the left eye. Previously, a retroperitoneal liposarcoma had been surgically removed followed by postoperative radiation. Visual acuity was normal. There was proptosis of the left eye, increased retrobulbar resistance and reduced mobility. Trans-septal orbital biopsies showed liposarcoma. The patient was initially treated with prednisolone and later received radio- and chemotherapy. Despite treatment he lost vision of the left eye and died a few months later. RESULTS: Histological examination of the orbital tumor revealed a spindle-cell liposarcoma similar to the primary tumor of the retroperitoneum. CONCLUSIONS: Liposarcoma metastatic to the orbit is rare, but should be suspected in a patient with proptosis caused by a space-occupying lesion and a history of liposarcoma.

The value of CA 125 measurement before second-look laparotomy in patients with ovarian carcinoma.

Serum CA 125 levels were evaluated in 71 patients undergoing second-look laparotomy for primary epithelial ovarian cancer. With a cut-off limit of 35 U/ml, 17 of 45 patients with residual disease (38%) were CA 125-positive. All of 26 patients with pathological complete response were marker-negative. Second-look laparotomy may be avoided in a select group of patients with elevated CA 125 values.