Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency - a worldwide patient survey.

BACKGROUND: The aim was to survey current practice in glucocorticoid replacement therapy and self-perceived health outcomes in patients with adrenal insufficiency. METHODS: Participants were recruited via patient organizations to respond anonymously to a web-based survey developed by clinical experts. Unique entries were set up for each patient organization enabling geographical localization of the entries. RESULTS: 1245 participants responded (primary adrenal insufficiency: 84%; secondary adrenal insufficiency: 11%; unsure: 5%). Therapies included hydrocortisone (75%), prednisone/prednisolone (11%), cortisone acetate (6%) and dexamethasone (4%). Dosing regimens were once daily (10%), twice daily (42%), thrice daily (32%) or other (17%). Compromised subjective health necessitating changes to physical activity or social-, work- or family life was reported by 64% of the participants. 40% of the participants reported absence from work/school in the last 3 months. Irrespective of diagnosis, 76% were concerned about long-term side-effects of therapy, mainly osteoporosis (78%), obesity (64%) and cardiovascular morbidity (46%). 38% of the participants had been hospitalized in the last year. CONCLUSIONS: Glucocorticoid replacement therapy among the respondents consisted primarily of hydrocortisone administered twice or thrice daily. A majority reported impact of their disease or treatment on subjective health requiring alterations in e.g. physical activity or family life. Three quarters reported concerns about long-term side-effects of the treatment. These data demonstrate - from the patients' perspective - a need for improvement in the management of adrenal insufficiency.

Wound complications in patients with carcinoma of the vulva. Comparison between radical and modified vulvectomies.

OBJECTIVE: To evaluate complications after different vulvectomies performed because of vulvar cancer. STUDY DESIGN: Retrospective analysis of 149 patients who underwent vulvectomy. RESULTS: Wound infections was found in 58%. Overweight, central or bilateral location of the tumor, and non-radical surgery were significant predictors of wound infections. Patients with a wound infection had more often wound breakdown (P<0.001), prolonged healing time (P<0.000), and lymphedema (P<0.001) than patients without infection. Antimicrobial prophylaxis did not prevent wound infection. Wound infections were found in 75% after radical en bloc vulvectomy (RV) and in 47% after modified vulvectomies (MV) (P<0.001). Also wound breakdown (47 versus 20%) (P<0.001) and lymphedema (48 versus 12%) (P<0.0001) were more common in RV group than in MV group. Lymphocysts were found in 7%, and showed no association with wound infection or type of operation. The mean hospital stay was 26 days in patients with wound infection and 12 days in patients without infection, 31 days in RV group and 12 days in MV group, respectively. CONCLUSIONS: Wound infections are major determinants for both acute and late complications. Postoperative complications reduce with increasing use of modified vulvectomies.

Pre-operative serum level of tumour-associated trypsin inhibitor and residual tumour size as prognostic indicators in Stage III epithelial ovarian cancer.

OBJECTIVE: To evaluate the use of the pre-operative tumour-associated trypsin inhibitor (TATI) level and residual tumour size at primary surgery as a prognostic indicators for patients with Stage III epithelial ovarian cancer. DESIGN: Retrospective cohort study. SETTING: Department of Obstetrics and Gynaecology, University Hospital, Helsinki, Finland. PARTICIPANTS: Ninety-eight women with Stage III ovarian cancer. METHODS: TATI was measured by radioimmunoassay from serum samples obtained within one week before surgery. A cutoff value of 22 microg/L was used. Multivariate analysis included pre-operative TATI level, age, histologic grade and histologic type. Mantel-Cox test was used for calculating statistical significance of differences in survival between groups. MAIN OUTCOME MEASURES: Cumulative five-year survival, pre-operative serum TATI level and residual tumour size. RESULTS: Surgery was optimal (residual tumour size < or = 2 cm) in 55 patients and suboptimal (residual tumour size > 2 cm) in 43. Pre-operative TATI level < or = 22 microg/L predicted better prognosis both in patients with optimal and suboptimal surgery compared with patients with pre-operative TATI level > 22 microg/L. Patients with optimal surgery and a pre-operative TATI > 22 microg/L had a twofold relative risk of death compared with those with a pre-operative TATI < or = 22 microg/L. The cumulative survival was less than three years for patients with suboptimal surgery and pre-operative TATI > 22 microg/L. CONCLUSIONS: Pre-operative serum TATI in combination with residual tumour size may be useful in stratifying patients with Stage III ovarian cancer into different categories in randomised treatment trials.

Therapeutic and prognostic considerations in primary carcinoma of the vagina.

We analyzed 46 patients with primary carcinoma of the vagina treated between 1969 and 1990. Median age of the patients was 67 years (range 33-89 years). Most (52%) of them were obese and 35% were nulliparous. Four (9%) had suffered from other gynecologic carcinoma and had been operated six to 23 years before the current carcinoma. Forty (87%) patients had squamous cell carcinoma. Stage 0 (carcinoma in situ) was found in three (7%) cases and stage I-IV in 21 (54%), 10 (22%), four (9%) and eight (17%) cases, respectively. Most (81%) of the patients were treated with radiotherapy (alone or in combination with other treatments): combination of brachytherapy and external radiotherapy were used in 45% of the cases. Surgery was used in all stage 0 cases and in 52% of stage I cases. Recurrence of the disease was found in 20 (43%) cases during the follow-up of 10 years. Most often (40%) site of the recurrence was the vagina. Both 5- and 10-year survival were 38%. Stage and extent of the tumor were independent prognostic factors in stepwise multivariate analysis.

Endometrial adenocarcinoma with clinical evidence of cervical involvement: accuracy of diagnostic procedures, clinical course, and prognostic factors.

BACKGROUND: The accuracy of clinical staging is known to be insufficient in stage II endometrial carcinoma. Also the optimal management of this disease is controversial. In this study we evaluate diagnostic accuracy and prognostic factors with special reference to treatment modalities of stage II endometrial carcinoma. METHODS: Of 1297 patients with endometrial adenocarcinoma (EAC) treated between 1970 and 1980 at Departments of Obstetrics and Gynecology, Helsinki University Central Hospital, 140 (11%) cases represented clinical stage II and were retrospectively analyzed. RESULTS: Median age of the patients was 63.5 years (range 40-85 years). Accuracy of Papanicolaou smear was 50%, and that of endocervical curettage 51%. Most of the tumors were histopathologically pure adenocarcinomas (88%), well differentiated (43%), and superficially invaded to myometrium (44%). Thirty-four (24%) of the patients developed a recurrent disease during the first five years afterwards. Median time of recurrency was 17 months (range 4-35 months). The disease free 5- or 10-year survival were 72% and 67%. Survival was significantly correlated with menopausal state (p < 0.01), tumor grade (p < 0.05), myometrial invasion (p < 0.001), surgical stage (p < 0.0001), and mode of treatment, i.e. operation done or not (p < 0.05). Survival was not affected by the radical nature of the operation (radical vs. simple hysterectomy). When all prognostic variables were analyzed by Cox's regression model (multivariate analysis) in 10-years follow-up, only menopausal state, myometrial invasion, and mode of treatment, i.e. operation done or not (p < 0.01), were independent prognostic factors. CONCLUSIONS: The only relevant staging procedure is the histological examination of cervix without the preoperative irradiation. According to our results it seems that simple hysterectomy instead of radical (Wertheim operation) hysterectomy may be a sufficient operative treatment of stage II endometrial carcinoma.

Tumour-associated trypsin inhibitor (TATI): comparison with CA125 as a preoperative prognostic indicator in advanced ovarian cancer.

We have evaluated the prognostic value of tumour-associated trypsin inhibitor (TATI) in stage III or IV ovarian cancer. Tumour-associated trypsin inhibitor (TATI) and CA 125 were determined in serum samples from 66 patients taken before primary surgery. TATI was elevated (> 22 micrograms l-1) in 27 patients (41%). These had a 5 year cumulative survival of 8%, whereas survival was 45% in 39 patients with normal preoperative TATI values. By contrast, the preoperative CA 125 level did not predict survival. In multivariate analysis which included age, stage, histological grade and preoperative TATI and CA 125 levels, patients with elevated preoperative TATI levels had a 2.3-fold relative risk of death (95% confidence interval 1.23-4.20; P = 0.002) compared with patients with normal preoperative levels. This result was comparable with the predictive value of primary residual tumour size, since patients with residual tumour larger than 2 cm in diameter had a 5.2-fold relative risk of death (95% confidence interval 2.55-10.68) compared with patients with a smaller or no residual tumour. Thus, preoperative determination of serum TATI may have a place in the pretreatment evaluation of patients with advanced ovarian cancer.

Radiotherapy of malignant melanoma of the uvea with I-125 seeds.

Nineteen patients with malignant uveal melanomas were treated with I-125 applicators. There were 10 males and 9 females with a median age of 61 years (range 42-76). The tumour was located in the choroid in 12 eyes and in the choroid and ciliary body in 7 eyes. The size of the tumours was 7-18 mm in maximal basal diameter (median 12), 5-16 mm in minimal basal diameter (median 10), and 5.5-15 mm in thickness (median 8.5). The volume of the tumours was 123-1890 mm3 (median 540). All tumours were classified as large (T3). For the irradiation, a computer program, which calculates three-dimensional dose distribution of I-125 seeds in gold plaques, was developed. By modifying the seed positions, activity and the orientation, patients can be treated individually. Iodine-125 emits low energy photons, ideal for intraocular tumour therapy and tissue. Extra-ocular tissue located behind the applicator can be completely shielded by a 0.5 mm gold layer. The dose at the apex of the tumour ranged from 30 to 120 Gy (median 93). The treatment time ranged from 44 to 600 h (median 235). Preliminary results are good. After a median follow-up of 6 months, the tumour growth has been arrested in all eyes and in 10 eyes the tumour has decreased in size.

Endometrial carcinoma in the cancer family syndrome.

The study group consisted of 26 women with endometrial adenocarcinoma belonging to 19 cancer families. Age at the onset of cancer, the stage and histologic differentiation of the tumor, initial symptoms, other malignancies, 5-year survival, and transmission of cancer to descendants were studied. The focus was on the importance of endometrial carcinoma in the tumor spectrum. The diagnosis of cancer family was delayed in 14 of the 19 families because endometrial carcinoma was not included in the primary diagnostic carcinoma. This delay may have been harmful to 16 family members who had carcinomas later in life. In ten of the 14 women with multiple malignancies, endometrial adenocarcinoma was the primary malignancy diagnosed, thus enabling the suspicion of a gene carrier and screening for subsequent malignancies. The authors concluded that endometrial carcinoma is a significant component of cancer family syndrome and should be included in the main criteria of Lynch syndrome II.

Deoxyribonucleic acid flow cytometric analysis of cervical adenocarcinoma: prognostic significance of deoxyribonucleic acid ploidy and S-phase fraction.

Paraffin-embedded tumor samples from 125 patients with cervical adenocarcinoma were analyzed by deoxyribonucleic acid flow cytometry. Thirty-one percent of the tumors were aneuploid. Triploid deoxyribonucleic acid content predominated (51.3%) and one third of the deoxyribonucleic acid aneuploid tumors were tetraploid, whereas near-diploid deoxyribonucleic acid aneuploidy was seen infrequently. Deoxyribonucleic acid aneuploidy was associated with tumor size, histologic grade, clinical stage, and high S-phase fraction. Deoxyribonucleic acid ploidy and S-phase fraction value were independent prognostic parameters, together with the presence of lymph node metastases and tumor size. In conclusion, our results indicate that flow cytometric deoxyribonucleic acid analysis helps to predict the prognosis and may thus influence the choice of treatment.

Adenocarcinoma of the uterine cervix.

In Finland, the incidence of cervical cancer has shown a decreasing tendency since the 1960s. The same trend, however, has not been noticed in the incidence of cervical adenocarcinoma. The reason for this is not known, although many studies have shown differences in the cause, epidemiology, and biology of the epidermoid and adenocarcinoma of the uterine cervix. A total of 106 new patients with cervical adenocarcinoma were treated at our institution from 1976 to 1980, which represents 20.4% of all cervical carcinomas treated. The mean age of the patients was 58.1 years (range, 29 to 82 years) and the peak incidence was in the group 60 to 69 years of age. Most of the patients were postmenopausal (71.7%) and the main symptom was abnormal vaginal bleeding (78.3%). The proportion of Stage I was 61.3%. Combined operative and radiation therapy was used in 74.5% of the patients. The overall 5-year survival rate was 65.1% (corrected 74.5%), which did not differ from that of patients with squamous cell carcinoma. The most significant prognostic factors were the size of the tumor, presence of pelvic lymph node metastases, and the stage of the disease.

Increase of cervical adenocarcinoma: a report of 520 cases of cervical carcinoma including 112 tumors with glandular elements.

A total of 520 new cases of cervical carcinoma were treated at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, in 1976 through 1980. Of these carcinomas, 95 (18.3%) were pure adenocarcinomas and 17 (3.3%) represented adenosquamous tumors. The mean age was 58.9 years (range 23-88 years). The age distribution was similar in patients with and without malignant glandular elements and the peak incidence was in the age group 60-69 years. In patients with adenocarcinoma, stage I was overrepresented (62.1%) whereas epidermoid carcinomas were more evenly distributed among various stages. The overall 5-year survival rate was 63.1%, with the corresponding corrected rate being 69.1%. The survival rate for patients with adenocarcinoma did not differ significantly from that for patients with squamous cell tumor. It is concluded that in our population the increasing frequency of cervical adenocarcinoma has not influenced the favorable results of the 5-year study. This disease, however, deserves more attention since its etiology, pathogenesis, and biology are still largely unresolved.

Effect of exercise on placental blood flow in pregnancies complicated by hypertension, diabetes or intrahepatic cholestasis.

The effects of a standardized exercise test on intervillous placental blood flow were studied in 13 hypertensive, 10 diabetic and 8 cholestatic pregnant women in late pregnancy, and the results were compared with those of a normal control group. Analysis of variance for repeated measures revealed that in all the pathologic groups, placental blood flow was lower than in the controls. In all groups placental blood flow rose slightly 1 min after the cessation of exercise. The diabetics showed a decreased placental blood flow 30 min after the cessation of the exercise test (p less than 0.02). In diabetics, a fall was found in stroke volume, from 63 +/- 12 ml (mean +/- SD) before the exercise to 53 +/- 11 ml 30 min after the cessation of exercise (p less than 0.05), and a rise in peripheral vascular resistance, from 1540 +/- 200 (mean +/- SD) dynes/cm5 before exercise to 1750 +/- 390 dynes/cm5 30 min after the cessation of exercise (p less than 0.05). Pre-eclamptic patients had a higher peripheral vascular resistance than had normal controls. Pre-eclamptic, diabetic and cholestatic patients had lower cardiac index values than the normal subjects. The difference was significant in the pre-eclamptic and diabetic patients at 30 min after the cessation of exercise. Maternal heart rate, and systolic, diastolic and mean arterial blood pressures rose significantly from values at rest to values at the end of exercise in all groups. One of the pre-eclamptic patients showed a 74% decline in placental blood flow 1 min after the cessation of exercise coincident with fetal bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of exercise on maternal hemodynamics and placental blood flow in healthy women.

Intervillous placental blood flow responses to standardized exercise during late pregnancy were studied using a Xenon technique in 25 healthy women. Thirteen of them were studied twice between the 32nd and 38th weeks of pregnancy, with mean 32 (range 22 to 40) days between the studies. At the end of a 6-min exercise, mean maternal heart rate had risen from 77 +/- 10 (SD) to 154 +/- 11 beats/min, amounting to 63% of maximal oxygen uptake. Stroke volume rose by 9%, cardiac output by 65% and cardiac index by 71% as a consequence of exercise, but peripheral vascular resistance declined by 41%. The placental blood flow was at a similar level after the exercise as before the exercise, being 95 +/- 19 (mean +/- SD) ml/min/100 ml of intervillous space before, 98 +/- 24 one min after, and 93 +/- 16 30 min after the cessation of exercise. No change was found in the level of placental blood flow between the 32-34th and 37-38th weeks of pregnancy. The placental blood flow had a positive correlation with maternal weight, mean arterial blood pressure and with diastolic blood pressure. Maternal heart rate, cardiac output, cardiac index, placental weight and the birth weight of the infant was not correlated with placental blood flow. It is concluded that in normal pregnancy a short submaximal exercise has little effect on placental blood flow measured after exercise.

A computer program for I-125 seed implant.

A computer program, written in FORTRAN, for I-125 permanent interstitial implants has been developed. After implantation, isocentric radiographs are taken using radiotherapy simulator (Siemens) in order to obtain two X-ray images of seeds on the same film. Honeywell DPS8 computer and Hewlett-Packard 7221A plotter are used for the dose calculation. The program calculates the dose distribution at the plane desired using 100 X 100 matrix.

Endometrial adenocarcinoma: clinical outcome in 881 patients and analysis of 146 patients whose deaths were due to endometrial cancer.

Throughout 1970-1975, 881 patients were treated at Departments I and II of Obstetrics and Gynecology, Helsinki University Central Hospital. They were treated mainly by using surgery and/or radiotherapy combined with adjuvant progestin therapy. The over-all uncorrected 5-year survival rate was 72.2% and corrected rate was 82.1%. In 146 out of 245 cases death was due to endometrial cancer, and this group was analyzed separately.

Changing pattern of cervical carcinoma: a report of 709 cases of invasive carcinoma treated in 1970-1974.

Seven hundred and nine new cases of carcinoma of the uterine cervix were treated by surgery, radiotherapy, or both at Helsinki University Central Hospital between 1970 and 1974. Of these, 241 (34.0%) died of the disease during the 5-year follow-up period. Three hundred and eighty-three (53.9%) of the patients were operated on and in 112 (29.3%) of them the stage of the disease had been underestimated preoperatively. This was mainly due to the undetected lymph node involvement observed first at operation in 72 cases (18.8%). In 237 of the patients carcinoma was confined to the cervix according to findings at operation but in 24 (10.1%) of them a relapse or metastasis was observed within 5 years. Comparison of the results for 1970-1974 with those from the same hospital for 1926-1969 revealed a reversal in the steady improvement in the total 5-year survival rates. It is concluded that, even if the incidence of cervical carcinoma in Finland is to decrease, the prognosis for the disease may become poorer. This is mainly due to a shift in the peak incidence of cervical carcinoma to older age groups. Also a mass screening program is likely to decrease the relative number of slowly growing, less aggressive type of the disease.