Health technology assessment in Finland.

Finland has a long tradition of supporting social programs that promote equality and the welfare state. The healthcare system is financed mainly by taxation. Everyone is insured against illness. Each of Finland's five provinces is run by a provincial government that monitors the provision of social welfare and health care. However, the municipalities actually provide the services and regulate medical equipment and regionalization of services. During the early 1990s, gross domestic product (GDP) fell dramatically, and healthcare expenditure rose to 9.4% of GDP. Due to the economy's rapid recovery, the share of healthcare expenditure has again decreased and now matches the average level of OECD countries of approximately 7.7%. The former Finnish method of central planning and norm setting has guaranteed a fairly uniform development of necessary services throughout the country and free or low-cost access. Tight central planning did not, however, create incentives to contain costs. Therefore, in the beginning of the 1990s, decision-making power was largely decentralized to the municipalities, and the principles of state subsidies were reformed. In 1995, the Finnish Office for Health Care Technology Assessment (FinOHTA) was set up as a new unit of the National Research and Development Centre for Welfare and Health (STAKES). FinOHTA is intended to function as a national central body for advancing HTA-related work in Finland, with the ultimate goal of promoting the effectiveness and efficiency of Finnish health care. At present, the importance of HTA is widely recognized in Finland, especially in the face of rising healthcare costs.

Glassy carbon implant as a bone graft substitute: an experimental study on rabbits.

The purpose of this experimental investigation was to study the incorporation of porous glassy carbon in bone. Cylinders of porous glassy carbon were implanted in drill holes in diaphyses and metaphyses of rabbits tibia for 1, 3, 6, 12 and 24 weeks. Bone ingrowth into the glassy carbon implants was examined by radiographic, histologic, fluorocrome and microradiographic methods. The material caused no pathological reaction. Tissue ingrowth into pores was seen by all examination methods. The amount of bone in the pores increases with time. The ingrowth was most distinctive in those areas where the implant was in close contact with cortical bone or trabeculae of the cancellous bone. Porous glassy carbon can be used as bone substitute, although the small size of implant available is at the present a limitation for its clinical use.

Depletion of Langerhans cells in cervical HPV infection is associated with replication of the virus.

We studied the quantity of Langerhans cells in 36 patients with cervical human papillomavirus (HPV) infection. Significantly fewer Langerhans cells (p < 0.05) were found in patients with compared to those without DNA tetraploidy. Similarly, patients positive for HPV 16/18 DNA by in situ hybridization or antipeptide IgA antibodies to HPV 18 tended to have fewer Langerhans cells than those negative for HPV 16/18 DNA or IgA antibodies. Our results suggest that depletion of Langerhans cells is associated with productive HPV 16/18 infection in the cervical epithelium.

Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase fraction. A proposed classification of DNA histograms in breast cancer.

To optimize the prognostic value of DNA flow cytometry in breast cancer the authors calculated several parameters from the DNA histogram, including the DNA index, the size and number of aneuploid peaks as well as S-phase and G2/M-phase cell cycle fractions. Of these, DNA index and S-phase fraction (SPF) proved to be the most valuable prognostic indices. DNA aneuploidy was associated with a three-fold risk of death as compared to DNA diploidy (P less than 0.0001). The highest risk of death was associated with hypertetraploid (greater than 2.20) DNA index, whereas a tetraploid DNA index (1.80-2.20) was associated with a relatively low risk. The SPF had significant additional prognostic value in both DNA diploid (P = 0.0002) and DNA aneuploid (P = 0.02) tumors. By combining DNA index and SPF the authors defined three types of DNA histograms, which were associated with favorable, intermediate, and poor prognosis of the patients. DNA diploidy together with low (less than 7%) SPF (type I DNA histogram) was associated with very favorable prognosis, whereas DNA aneuploidy with high DNA index (greater than 2.20) or high (greater than 12%) SPF (type III DNA histogram) was related to the worst prognosis with approximately eight-fold relative risk of death. In a Cox multivariate regression analysis the type of DNA histogram was an independent and most powerful prognostic indicator in breast cancer. The other independent factors in the Cox analysis were primary tumor size, nodal status, and progesterone receptor status.

Tumour DNA ploidy as an independent prognostic factor in breast cancer.

We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P less than 0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer, primarily in cases with steroid receptor-positive tumours. In a Cox multivariate analysis DNA ploidy (P = 0.001), primary tumour size (P = 0.0007), nodal status (P = 0.04) and the content of progesterone receptors (P = 0.0008) emerged as significant independent prognostic factors, whereas oestrogen receptor status, age and menopausal status of the patients had no significant independent prognostic value. If the histological grade of ductal carcinomas was also included in the Cox model, both grade and DNA ploidy had independent prognostic effect. In conclusion, our results indicate that the analysis of DNA ploidy is a useful adjunct in the assessment of prognosis for breast cancer patients.

Aneuploid DNA content and high S-phase fraction of tumour cells are related to poor prognosis in patients with primary breast cancer.

The prognostic impact of DNA content and S-phase fraction (SPF) of tumour cells was studied in 93 patients with primary breast cancer. Aneuploid DNA content and high SPF were clearly associated with poor differentiation state of tumours and absence of steroid, especially progesterone receptors. Aneuploidy and high SPF tended to become more common with increasing primary tumour size, with more extensive nodal involvement and with more advanced stage of the cancer. Patients with diploid tumours had a slightly longer disease-free interval and survival than those with aneuploid tumours, whereas below median SPF as compared to above median SPF was associated with significantly longer (P less than 0.01) relapse-free interval and survival in patients with stage II-III cancer. We conclude that the DNA analysis of tumour cells is a promising method for the estimation of prognosis in breast cancer patients.

Light- and electron-microscopic findings in lichen sclerosus of the vulva during etretinate treatment.

Fifteen women with lichen sclerosus (LS) of the vulva were treated for 3 months with 0.6 mg/kg of etretinate. The clinical response was good in 11/15 of the patients and, in agreement with this, light microscopy showed decreasing atrophy and hyperkeratosis together with subsiding inflammatory changes. However, orcein staining demonstrated that even after etretinate treatment, elastic fibers were still absent in the upper dermis with only few fibers being detectable in some specimens. Conventional electron microscopy and immunoelectron microscopy were used to examine these changes more in detail. Antiserum to the microfibrillar part of the elastic fibers confirmed that only remnants of microfibrillar coat persisted in the upper dermis and that deeper in the dermis, elastic fibers were porous and fragmented. These findings demonstrate that despite the normalization of clinical and certain histological parameters during etretinate treatment, the initial elastic fiber damage persists both at the light- and electronmicroscopic levels.

[Oral treatment of vulvar dystrophy with an aromatic retinoid, etretinate]. / Orale Behandlung der Dystrophie der Vulva mit einem aromatischen Retinoid, Etretinat.

Twenty patients with vulvar dystrophy (19 Lichen sclerosus, 1 Lichen ruber planus) were treated for 3 months with etretinate (Tigason) with an initial dose 0.54 mg/kg/day, maintenance dosage 0.26 mg/kg/day. All the patients had been unsuccessfully treated previously with topical oestrogen and corticosteroids. The therapeutic effect of etretinate on the subjective and objective symptoms of the disease was excellent. In most of the patients the pruritus and burning symptoms diminished within 2 weeks of treatment, and after 3 months the grade of symptoms was lower in 95% of cases. Clinically, a decrease in severity was achieved in 93% of cases among the group with severe vulvar dystrophy. The therapeutic effect of etretinate is strongly anti-inflammatory and it has a powerful effect on the epidermal tissues. According to the latest studies, etretinate also has a strong immuno-modifying effect on the epidermal cells. The secondary inflammatory changes, such as excoriatia, fissures and superinfections disappeared. In the histopathological follow-up hyperkeratosis in the stroma diminished and the inflamed cells and connective tissue normalised after 3 months of treatment. Side effects included cheilitis, dryness of mucous membranes and slight loss of hair. It must be taken into account that etretinate may cause liquid metabolism disturbances, particularly among risk factor patients (diabetes, obesity etc.). In our experience the best results to date in the treatment of vulvar dystrophy can be achieved with etretinate. Due to the teratogenic effect of etretinate, a reliable method of contraception must be used by fertile women of childbearing age.

Clinical pathology of acute necrotising pancreatitis.

Seventy nine pancreatic specimens were obtained from patients treated with pancreatic resection for acute necrotising pancreatitis. The necrotising process had started in the periphery of the gland, so that eight of seventy nine cases contained peripancreatic (mainly fat) necrosis only without any parenchymal necrosis. Peripheral parenchymal necrosis was characterised by a severe inflammatory reaction, with multinucleated leucocytes and microabscess. In the deep parts of the pancreas coagulation necrosis was found. Vascular changes (thrombosis, vessel necrosis) correlated with postoperative haemorrhagic complications, but they did not seem to have any important role in the necrotising process. The vascular changes seemed to be a secondary phenomenon. In clinical practice the most important aspects in reporting the histology of acute necrotising pancreatitis are the extent of parenchymal necrosis, because the surgeon may overestimate its extent, and the existence of vascular changes, because of the correlation with postoperative recovery.

Bone growth into glassy carbon implants. A rabbit experiment.

This study was designed to evaluate the growth of bone into porous glassy carbon cylinders. Porous carbon cylinders were implanted in 30 rabbits intra-articularly in the metaphysis of the femur opposite from the patella. The rabbits were sacrificed up to 24 weeks after the operation. The bone samples were examined by histologic, fluorochrome and microradiographic methods. The amount of bone ingrowth was measured histomorphometrically. Fluorochrome uptake was seen in the implant pores, which indicated new bone growth originating from surrounding bone. After 3 weeks, microradiographs revealed new bone formation in the pores and with time the bone spicules became more dense. The amount of bone tissue in the pores grew and reached a maximum at 12 weeks, when 45 per cent of the total pore volume was incorporated with bone tissue. No adverse tissue responses were observed.

Uterine sarcomas.

During 1962-1980, 44 uterine sarcomas were treated at the Department of Obstetrics and Gynaecology of Tampere University Central Hospital. Of the sarcomas, 35 (79%) were leiomyosarcomas, six (14%) endometrial stromal sarcomas and three (7%) endometrial carcinosarcomas. The 5-year survival for patients with leiomyosarcoma was 51 per cent. The 5-year survival rate for the premenopausal patients was 73% and that for postmenopausal patients 20%. The most important prognostic indicator was the gross presentation of the tumor at the time of surgery. Of the 5-year survival patients 94% were of clinical Stage I and of the failed patients 55%, respectively. Rather poor correlation was noted between the mitotic activity and survival rate. Metastases to the lungs were the most common failure pathway. All six patients with endometrial stromal sarcomas died within 25 months after the diagnosis. High oestrogen and progestin receptor concentrations were demonstrated in the endometrial stromal sarcoma.

Primary malignancies of the fallopian tube.

Ten cases of primary adenocarcinoma of the fallopian tube occurring over 23 year period are presented. The mean age of the patients was 61.2 +/- 9.2 years (range 48-77). Eight of the patients were postmenopausal. Abnormal vaginal bleeding was the most common symptom and was present in six patients. A pelvic mass was detected in seven cases. In one of the patients abnormal vaginal cytology was leading to correct diagnosis. The problem of the disease is a late diagnosis. Eight of the ten patients with tubal adenocarcinoma represented clinical Stage III or IV. Four of the patients are alive more than ten years after the diagnosis. A rare case of carcinosarcoma of the fallopian tube is presented. Only 26 such cases have been described in the literature to date. In addition a case of tubal choriocarcinoma is reported.

Interaction of microporous glassy carbon and living tissue.

Preliminary animal implantation tests with rats showed that microporous glassy carbon has good biocompatibility. Microporous glassy carbon is also stable and suitable for a hard biocompatible implant.

Independent risk factors of benign and malignant breast lesions.

The purpose of this study is to evaluate the risk factors of benign breast disease and to compare them with the known risk factors of breast cancer in order to make inferences on the relationship between benign breast disease and breast cancer. All benign breast lesions diagnosed from the population of the city of Tampere, Finland in 1974-1977 were reclassified by two pathologists into two groups of dysplasias and two groups of tumors. In the risk analysis of 422 age-matched pairs no group of benign lesions had risk factors consistently similar to those of breast cancer. It is therefore likely that either benign breast disease is not associate with breast cancer or it is an independent risk factor, not associated with the other high risk indicators of breast cancer.

Clinicopathologic and histochemical study of ovarian clear cell carcinoma.

Thirteen case reports of mesonephroid clear cell carcinoma of the ovary were analyzed and nine of the tumors were studied histochemically. No disorders were found in the hormonal balance of patients. The tumors produced few symptoms, indicating late discovery and bad prognosis. Histopathologically, the tumors were subdivided into the following groups: glandular, papillary, mixed-type and anaplastic. All of them contained glycogen and neutral mucins; acid mucins were found mainly in glandular tumors, which contained more sulfomucins than carboxymucins. Generally, the most active glandular tumors did not produce sialomucins. No clear correlations between prognosis and clinical pictures, morphology or constitution of cell excretions were found.

Resection of the pancreas for acute hemorrhagic and necrotizing pancreatitis.

The role of surgery in the treatment of acute hemorrhagic or necrotizing pancreatitis is discussed on the basis of a series of 996 patients with all types of acute pancreatitis who were treated in the years 1967--1976. Pancreatic resection was performed in 29 patients with hemorrhagic or necrotizing pancreatitis during the past 3 years. The extent of resection ranged from 60 to 100% of the pancreas. Eight patients died, for a mortality rate of 28%. Eight of 21 surviving patients developed diabetes requiring substitution therapy. During a follow-up period of 6 to 36 months, 17 patients were able to resume work, 3 are still convalescing, and 1 has retired.

Placenta as an indicator of fetal postnatal prognosis.

468 placentas were studied microscopically and by gross examination. Velamentous insertion of the umbilical cord, placenta circumvallate, retroplacental hematoma in connection with ablation of the placenta, and cord prolapse were found to be causative factors in asphyxia of the newborn. The increased placental weight was characteristic in maternal diabetes, hepatosis and, sometimes, in cases of infant malformations and specific inflammations. So-called embryonal persistence was often found histologically in these changes. Small fibrous placentas and those with ramification defects were commonly encountered among cases of toxemia and prolonged gestation. Microscopical placental maturation defects were not indicative of the fetal condition. Thus, only the changes found at gross examination appeared to be a significant indicator of the fetal prognosis.