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Sixty-five patients with Stage I and II endometrial carcinoma were investigated. After a short-time follow-up (17-24 months) significant differences in frequency of relapses were observed between patients with tumors containing low amounts of estrogen receptor (ER less than 60 fmol/mg DNA) in the nuclear pellet, and those with tumors containing greater than 60 fmol ER/mg DNA (p = 0.01). Other prognostic factors showed no differences in frequency of relapses. In this small patient material with a short-time follow-up we therefore suggest that ER in the nuclear pellet may be an important prognostic factor.

Eighty-six patients with invasive squamous cell carcinoma of the vulva stage I were followed for 2 to 20 years after surgical treatment varying from local excision to radical vulvectomy with inguinal lymph node dissection. The results are presented and the prognosis discussed in relation to the radicality of the surgical intervention, the degree of tumour differentiation, the morphologic properties of tumour cell population, and the tumour host relationship. The most important prognostic factor seemed to be the radicality of the surgical intervention. To reduce patient morbidity in radical surgery while still achieving a comparable survival rate an operative approach with less than radical vulvectomy, inguinal dissections or pelvic lymphadenectomy, or both, is proposed for selected patients.

Two materials consisting of patients with early invasive squamous cell carcinoma of the uterine cervix have been studied in regard to the influence of age and treatment technique on prognosis. In the first material, consisting of 254 Stage Ib patients treated only with radiation therapy, a poorer prognosis was found in the women under 35 years of age. The second material consisted of 274 Stage Ib patients who had been preoperatively irradiated and had undergone radical hysterectomy. The prognosis was (not significantly) better for those patients under 35 years of age in this group. The rate of central recurrence was higher among the younger patients who received only radiation therapy. Analysis of histologic grading and cell type according to J. W. Reagan and S. F. Yao (Int. J. Radiat. Oncol. Biol. Phys. 5, 1015-1020 (1979) ) revealed no explanation for the poorer prognosis among younger women treated solely with radiation therapy.

Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes.

A prospective randomized trial was carried out in 153 patients with stage III malignant epithelial tumours for comparing the effects of irradiation or combination of chemotherapy and irradiation on prognosis and operability. No significant differences between these two treatment modalities were found. Of the patients primarily considered inoperable were 41 per cent operated upon after preoperative treatment. Minimum residual disease (0 to less than or equal to 2 cm) occurred in 38 per cent of the primarily operated and in 31 per cent of those operated upon after preoperative treatment. Preoperative irradiation in primarily inoperable patients enabled more effective surgical measures at relaparotomy. The size of the residual tumour after surgery and the tumor grade influenced the survival.

Dose distribution around intracavitary applicators (Stockholm technique) has been investigated. The gradient of dose around the combination of intrauterine and vaginal applicators used is steep. The position of the uterus with and without the radium applicators inserted varies. Together with the steep dose gradient this implies that external irradiation following intracavitary treatment involves a risk for overdosage to tissues in the vicinity of the uterus and underdosage to the parametrium.

A total of 555 cases of malignant epithelial ovarian tumour diagnosed in vivo was reported to the Regional Tumour Registry for Southern Sweden, Lund during 1974-1978. Of these 428 (77%) were referred to the Department of Oncology, Lund, which serves the Southern Swedish Health Care Region. Patients not being referred were mostly elderly with advanced tumours. The selection of patients will thus affect the evaluation of the treatment results. The standard surgical procedure was bilateral salpingo-oophorectomy with or without hysterectomy, and infracolic omentectomy. 95% of the patients were treated according to a randomized trial including postoperative chemotherapy, radiotherapy or a combination of both. Preoperative radiotherapy in primarily inoperable patients increased the operability. 34% of all stage IIb, IIc, III, and IV-patients were thus operated or reoperated with only small residual tumour or none at all following surgery. Stage, grade and size of postoperative residual tumour were the most important prognostic factors. The five-year cumulative survival rate for all patients referred to the Department of Oncology was 32%.

Twenty patients with advanced and/or recurrent vulvar carcinoma were treated with bleomycin alone or combined with mitomycin C. Five of 11 patients in the bleomycin-treated group showed objective response (two complete and three partial) and five of nine patients in the bleomycin-mitomycin C-treated group showed objective response (one complete and four partial). No severe side effects were seen. Now that activity against this disease has been demonstrated for bleomycin, alone or combined with mitomycin C, attention should be directed to treating those patients not cured by surgery and radiation therapy alone.

Hysterography was used for judging the size and location of the primary tumor in 475 patients with stage I carcinoma of the uterine body. No increased frequency of recurrence and metastases was noted in patients where the tumor involved the uterine cervix. Large tumors, however, were accompanied by an increased frequency of recurrences, metastases in the pelvic nodes and remote metastases.

In a material of 21 patients including 7 primary and 6 recurrent vulvar carcinomas, 5 vaginal carcinomas, 1 urethral carcinoma and 2 preinvasive vulvar carcinomas operation was performed with a CO2-laser scalpel. In 9 radical and 3 partial vulvectomies no primary closing of the wounds was performed. In the remaining primary closing was performed. The operative bleeding and healing process with laser scalpel and electrosurgical scalpel using open wound technique were about the same. The surgical time was longer with the laser technique but the operative specimens were better preserved. Healing of the primary closed wounds were uncomplicated.

In 23 (about 43%) patients cytologically screended within 4 years before the diagnosis invasive cervical cancer 11 had a benign smear; when reviewed, two were borderline cases and three were misinterpreted. Twelve patients had different degrees of squamous cell dysplasia. In three of these the cancer was detected during the follow up procedures. Four did not respond to calls for follow up. Five were checked without any active measure but sampling new smears. Atypical smears must be clinically evaluated and treated in order to detect invasive carcinomas. The therapeutic results, however, may be controlled by repeat smears.

Central recurrence was recorded during 1963-1972 in 136 patients (14%) out of a group of 977 cases given radiation therapy for carcinoma of the uterine cervix (Stages I and II). Fifty of these patients (i.e. 37%) showed indications for surgery. In 12 of them only explorative laparotomy was performed. Radical hysterectomy was carried out in 14 cases, combined vaginal and abdominal wide extrafascial hysterectomy in 13 cases and ordinary extrafascial hysterectomy was chosen in 11 cases. The cellmorphology in the squamous-cell cancers, classified according to Reagan et al., was proportionally the same in these patients as in the series as a whole. The patients operated on by combined vaginal and abdominal hysterectomy had the same rate of survival, but fewer complications, than those given radical hysterectomy.

Six hundred and forty-four patients with primary malignant tumours of the female genital tract were subject to a two-stage screening program on admission, with clinical examination in all and mammography in 380. Clinical examination alone revealed 4 cancers, while supplementary mammography screening of 369 patients with normal clinical examination revealed an additional 6 tumours, of which 5 were invasive. The prevalence rate was about three times that found in two mass-screening programs in different parts of Sweden. Thus, it could be concluded that there is an increased risk for mammary carcinoma in patients with gynaecologic malignancies. It seems reasonable therefore, to recommend mammography routinely in this group of patients.

Twenty-five patients with malignant vulvar melanoma have been treated with radical vulvectomy using the warm knife-open wound technique. Following preoperative radiation therapy, dissection of the groin and, in some cases, pelvic lymphadenectomy, were performed as a second procedure. Crude five-year survival was 9/21 (approximately 43%). Patients with tumours of Clark level II--IV have been found to have a good prognosis (7/9), while those with Clark V-tumours have had an extremely poor prognosis (2/10). Prophylactic dissection of the inguinal nodes has not been found to improve the prognosis, and pelvic lymphadenectomy is considered to be inadvisable.

In the present phase II trial 18 heavily pretreated patients with advanced ovarian malignancy were treated with spirogermanium, 11 im and seven iv. Objective responses (partial remission) were obtained in two (11%) of the 18 patients, with a remission duration of 5 and 23 + months, respectively. An additional four (22%) patients had stable disease. Each of these six patients had a better quality of life. There were few side effects. Myelosuppression, nausea, or other gastrointestinal side effects did not occur. The present investigation shows that spirogermanium is useful as a palliative chemotherapeutic agent in patients with advanced ovarian malignancy.

A series of 244 patients with vulvar squamous cell carcinomas was analyzed with regard to treatment of the regional lymph nodes. In 144 patients, groin dissection was performed, supplemented in 24 cases by pelvic lymphadenectomy. Preoperative irradiation was given and in cases with positive nodes postoperative irradiation as well. Patients in whom lymph node dissection was not performed received irradiation. Treatment failures in the regional lymph node regions were analyzed and the policy concerning treatment of the regional lymph nodes is discussed.

The correlation between certain prognostic factors and the 10-year survival/lethality rate was analysed in 168 patients with invasive squamous cell carcinoma of the uterine cervix stage I A-II B treated by radiation therapy from 1969 through 1970. These factors included a malignancy grading system (MGS) consisting of 8 items: structure (P1), differentiation into cell type (P2), nuclear polymorphism (P3), mitosis (P4), mode of invasion (P5), stage of invasion (P6), vascular invasion (P7), and host-cellular response (P8). Histologic differentiation (1) and differentiation into cell type (11), the patient's age, the year of admission, the clinical stage (FIGO), and irradiation were also analysed. Many of these factors were correlated to the prognosis. However, the MGS system was superior as a predictive factor. Patients with a low MGS score had an extremely good survival rate at both the 5- and 10-year controls. The patients with a high MGS score had approximately 55 per cent lethality at 10 years. The MGS was significantly superior to each separate item as well as to each predictive factor (p less than 0.05). Further, no other important predictive factor could be identified after the MGS had been included in the multivariate analyses.

The frequency of serious complications in the bladder and intestines in 674 patients irradiated for carcinoma of the cervix using three different techniques is reported. The first technique was the Stockholm technique, which gave 5% severe complications. In the other two, the patients received primarily external irradiation without central shielding, complemented with intracavitary treatment. Difficulties in the Stockholm technique and in techniques combining external high-voltage and intracavitary treatment were taken into account, and the frequency of serious complications decreased to less than 1%.

Patients with Stage III ovarian carcinoma were treated either with extensive initial surgery and postoperative radiation therapy (17 patients) or with a less extensive initial laparotomy, postoperative radiation therapy and relaparotomy (19 patients). Better results were obtained among the patients in the latter group.

Thirty-three patients with advanced cervical cancer (31 squamous cancer, two adenosquamous cancer) previously untreated with cytotoxic drugs, were treated with bleomycin, 5 mg daily, for seven days and mitomycin C, 10 mg, on day 8. This regimen was repeated four times at two-week intervals. All but one patient had previously been treated with radiotherapy; 36% of the patients had an objective response (five complete remission (CR), median duration 12 months; seven partial remission (PR), median duration six months). Severe myelosuppression occurred in nine patients. One drug-related death due to thrombocytopenia occurred. Three patients developed pulmonary fibrosis and one of them died of respiratory failure. The bleomycin-mitomycin C regimen has a definite but clearly limited effect in advanced cancer of the uterine cervix.

A clinical and histopathologic study of material from a series of 21 patients with basal cell carcinoma treated from 1960 until 1979 are reviewed. In 3 patients 'mixed' tumor was recorded. The histopathologic diagnosis: basosquamous carcinoma and the behavior of this carcinoma are discussed. The mean age of the patients was 76 years. Presenting symptomatology consisted primarily of bleeding, burning or itching, and ulcerations. No case of pure basal cell carcinoma gave metastasis to the regional lymph nodes, in no case could the cause of death be attributed directly to this kind of lesion. A conservative approach consisting of wide local excision is suggested.

In a material of 777 patients with carcinoma of the uterine body, Stages I and II, 115 (15%) had poorly differentiated tumours, and 662 (85%) moderately-to-well differentiated tumours. The five-year tumour death rate was 34% and 12%, respectively. No differences in local recurrences and metastases in the pelvis were recorded in the two tumour groups. On the other hand, distant metastases occurred in 23% of patients with poorly differentiated tumours, and only in 5% among patients with moderately-to-well differentiated tumours. Whether chemotherapy integrated in the treatment-scheme would reduce the frequency of distant metastases and improve the survival rate remains an open question.

The early diagnosis of ovarian carcinoma is as difficult and rare as ever before. Despite the appearance of sophisticated drugs and combinations of these with surgery and radiotherapy the prognosis still remains the same as during the last 30 years, i.e. overall survival between 20 to 30%. This study concerns the impact of prophylactic oophorectomy in Sweden. 4.6% of ovarian carcinoma patients had received pelvic surgery at some time prior to the diagnosis of ovarian cancer and after the age of 40. With the help of statistical data it is estimated that about one hundred out of the approximately thousand women per year who now develop ovarian cancer in Sweden could be saved if prophylactic oophorectomy were practised in our country. Various aspects of prophylactic oophorectomy and its effects are discussed. It is our opinion that every gynaecologist/surgeon should seriously take into consideration and discuss the possibility of prophylactic oophorectomy in the perimenopausal patient before operation. Not to perform prophylactic oophorectomy during pelvic surgery after the menopause seems to us to be an unreasonable practice.

In the present phase II trial, 26 heavily pretreated patients with advanced recurrent ovarian carcinoma were treated with tranexamic acid, 4-6 g per os daily for at least 3 months. Of these 26 patients, 3 had stage IIb, 21 stage III and 2 stage IV. Histologic examination revealed serous adenocarcinoma in 13, mucinous in 3, endometroid in 4, 1 anaplastic and 5 unspecified adenocancer. Twenty of the tumors were poorly differentiated and 5 highly-moderately differentiated. No objective response was noted but all the highly-moderately differentiated tumors showed a stable disease state with a median duration of 6 months (range 4-36 months). The patients with poorly differentiated tumors had a median survival of 4 months. Most of the patients had some form of gastro-intestinal side effect. This investigation has shown that treatment with tranexamic acid was not particularly helpful in poorly differentiated cases in which modern combined chemotherapy already had failed. The effect in highly-moderately differentiated cases needs further evaluation.

Twenty-four consecutive women with recurrence and/or metastasizing carcinoma of the cervix were treated with adriamycin and methotrexate. All patients had previously been treated with external irradiation and 2 intracavitary radium applications. The median recurrence-free interval was 22 months. All patients were evaluable. Five patients (21%) had partial remission for a median duration of 5 months (2 to 9 months), and 7 patients had static disease. When used in dosages that do not precipitate dangerous toxicity this therapy is not effective and in the authors' opinion should be abandoned.

Radical vulvectomy using warm-knife and open-wound techniques was performed as the first step in a two-phase surgical approach in 274 patients with malignant vulvar tumors. Crude 5-year survival was registered in 133/223 (60%) patients. The complication rate was low and the hospitalization period was short (mean 16 days).

A prospective randomized trial for comparing the effects of chemotherapy and radiotherapy on survival in malignant epithelial ovarian tumours was carried out during the years 1975-1978 in 142 (90%) of a total material of 157 patients in Stage I and Stage II of this disease. Stratification was done according to the state of the tumour capsule and the type of histology found in Stages Ia and Ib. Two types of randomized treatment were given: A. Patients with no extracystic excrescences and intact tumour capsule with mucinous tumours in Stages Ia and Ib were given Melphalan or were not treated, while those with non mucinous tumours were given Melphalan or radiotherapy; B. All of the other patients with tumours in Stage I and Stage II were treated with radiotherapy alone, or were irradiated in combination with Melphalan treatment. Both of these treatment groups had about the same rates of 2- and 5-year survival. It was seen that the histological grade and the amount of residual tumour left at surgery are important prognostic factors. Postoperative treatment does not seem to improve cases of well differentiated, early mucinous tumours in Stage Ia. Acceptable results were obtained, however, irrespective of histological type, in early Stage I, moderately differentiated tumours treated with Melphalan or radiation therapy, and in well- or moderately differentiated tumours in Stage I or Stage IIa using irradiation alone or in combination with chemotherapy. Stages IIb and IIc, and all poorly differentiated tumours in Stages I and II, require more aggressive treatment.

An analysis of 230 patients treated with radiotherapy for cervical cancer stages I and II is presented. No positive correlation to cell type was found as regards the number of failures, recurrence rate or the frequency of regional or distant metastases. Although different biological behavior might be shown by cancers of varying cell types, adequate planning and staging before treatment seems to be of better prognostic value.

Nineteen patients with recurrent endometrial carcinoma and one patient with Stage IV endometrial carcinoma not previously treated with chemotherapy were treated with a combination of doxorubicin and cisplatin. The dose schedule was doxorubicin, 50 mg/m2 on day 1, and cisplatin, 50 mg/m2 with hyperhydration on day 1, with a new course every 4 weeks. Objective response 60% was obtained in 12 out of 20 patients (two with complete remission and 10 with partial remission). Furthermore, four patients had stationary disease. The two patients with complete remission both had distal vaginal metastases, and they are still alive after greater than 21 and greater than 40 months. The median survival period for those with partial remission was greater than 11 months (range of 4 to 26); for those with stationary disease, 7 months (range of 4 to 10), and for those with progressive disease, 4 months (range of 3 to 7). The response rate was higher for well-differentiated tumors. No serious side effects were noticed. To our knowledge no other reports have been published so far with the use of the same regimen in patients with recurrent endometrial adenocarcinoma with no prior chemotherapy. We find the objective response rate, the survival time, and the quality of life for the responding patients in our study so encouraging that we shall continue with a larger trial.

Women treated with estrogen exhibit a higher risk of developing endometrial cancer. steroid hormones exert their effects on target tissue through specific cytosol receptor protein. Knowledge of this steroid receptor concentration in endometrial carcinoma might facilitate the treatment of recurrences. We have compared the concentrations of endometrial estrogen and progesterone cytosol receptors with the histologic grade of endometrial carcinoma as well as the rate of 3H-thymidine incorporation. We found a significant difference in receptor concentration between well-moderately differentiated tumours and poorly differentiated ones. No correlation was found between 3H-thymidine incorporation rate and differentiation. A positive correlation between thymidine incorporation rate and progesterone receptor concentration was noticed. The concentration of receptors varies within a wide range of each group of differentiation; thus 23% and 4% of the poorly differentiated tumours had higher concentration of estradiol and progesterone receptors respectively than the median values for well differentiated tumours.

Thirty-six patients with advanced ovarian carcinoma, 21 who had not responded to conventional surgery and irradiation therapy and 15 who had not responded to conventional surgery, irradiation therapy, and chemotherapy, were treated in a phase II study with Leo 1031. Objective responses were obtained in ten (28%) of the 36 patients (two complete and eight partial responses). An additional 11 (32%) patients had stable disease. The two complete responders were in remission for 4 months. During remission, all of the patients had an improved quality of life. Myelosuppression of varying severity occurred in 11 patients; three of these patients died from their complications. Two patients developed reversible confusion and one patient became psychotic. Eight patients became euphoric during treatment. Leo 1031 might be worthwhile as a palliative chemotherapy for patients with advanced ovarian carcinoma, but the risk of euphoria must always be considered since it can lead to voluntary overdosage.