[The value of etoposide (VP-16) in the therapy of refractory ovarian cancer]. / Die Wertigkeit von Etoposid (VP-16) in der Therapie des refraktären Ovarialkarzinoms.

In analogy to Kühnle et al. (1984) the role of etoposide in patients with cisplatin-refractory ovarian cancer was evaluated. 45 patients were treated with 150-200 mg of etoposide per sa. m. on days 1-3. Acute toxicity was tolerable except alopecia grade III. Remarkable, however, was the induction of two fatal cases of leukaemia following etoposide treatment. The first patient, who was 27 years old, with FIGO stage IIb serous cystadenocarcinoma, which was treated with cisplatin/epirubicin and after a latent period of 45 months, a local recurrence was treated with 8 cycles of etoposide. Twenty-three months after discontinuation of etoposide therapy, the patient showed acute myelogenous leukaemia (AML) of M5b-subtype according to the FAB classification. Two days after diagnosis, the patient died of the disease. The second patient, a 55-year old woman with FIGO stage IIa serous cystadenocarcinoma, was treated with cisplatin/cytoxan; 8 cycles of etoposide were given as a second line therapy. This patient, 21 months after discontinuation of etoposide therapy showed a pre-pre-B-acute lymphocytic leukaemia with coexpression of the myeloid antigens. Two months after diagnosis, the patient died of the disease. In 4 out of 38 patients, a complete and in 7 patients a partial remission was induced by etoposide treatment and survival of these responding patients was prolonged in comparison with the nonresponder. The survival was also dependent on CA-125 serum level and the cumulative dose of etoposide administered. Etoposide treatment is an acceptable option as salvage therapy in refractory ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

[Photodynamic therapy in patients with recurrent gynecologic cancers]. / Photodynamische Therapie bei Patientinnen mit Rezidiven gynäkologischer Karzinome.

Patients with recurrent gynaecological carcinomas have a poor prognosis, with a survival of a few months. Three patients with a recurrent vulva carcinoma, one patient with a recurrent cervical carcinoma, one patient with a recurrent endometrial carcinoma, and one patient with a recurrent breast carcinoma underwent PDT after parenteral or topical sensitisation with Photosan 3. From these patients, two of them showed a complete response with no evidence of disease for 32 and 29 months. One patient responded partially with two recurrences, which were treated twice after tropical sensitisation, living now 21 months. The remaining three patients showed partial response and died 3 to 8 months after PDT. The energy applied was derived from an argon-dye-laser ranging between 225 and 750 joule/cm2. Photosan 3 was given intravenously at a dose of 2.5 mg/kg body weight and was tolerated without any allergic reaction. The response rate in three of six patients in recurrent gynaecological malignancies encourages us to pursue PDT in gynaecological disease.

[Magnetic resonance tomography in follow-up of hydatidiform mole]. / Kernspintomographie zur Verlaufskontrolle der Blasenmole.

The value of magnetic resonance imaging (MRI) was studied in a case of a gestational trophoblastic tumour. In addition to the tumour size, MRI made it possible to measure necrotic areas, which are assumed to be a sign of response to chemotherapy. Moreover, uterine zonal anatomy and subserosal uterine veins yielded important information on tumour biology. Complete remission was induced in high-risk patients by etoposide, methotrexate, and actinomycin D treatment.

Neopterin, a marker of cell-mediated immune activation in human pregnancy.

High neopterin excretion is closely associated with activation of cell-mediated immunity. We studied urine and serum neopterin concentrations and serum interferon-gamma concentrations in normal pregnant women. In our study population, neopterin concentrations exceeded the normal range in 663 of 840 samples (79%). Neopterin levels increased with the time of pregnancy. Serum samples drawn from women in the third trimester of pregnancy also showed high neopterin concentrations in almost all cases; however, no circulating interferon-gamma was detected. Whereas neopterin is able to penetrate into the blood stream because of its small size (M = 253 D), diffusion of interferon-gamma is limited. Raised neopterin levels provide evidence for activated cell-mediated immunity during pregnancy.

[Comparison of conventional radium and high dose rate afterloading brachytherapy in cervix cancer]. / Vergleich der konventionellen Radium-mit einer High-dose-rate-Afterloading- Brachytherapie beim Zervixkarzinom.

The combination of intracavitary and external-beam radiation is the treatment of choice in advanced cervical cancer. Low-dose regimens using radium were widely abandoned in favour of high-dose-rate afterloading systems. We compared in this retrospective analysis of 550 patients the 2 different treatment modalities. We could observe neither in overall survival, nor in the incidence of side effects, any significant difference. Although the change from low- to high-dose-rate radiation therapy was not accompanied by a benefit in survival, the latter modality displayed several advantages e.g. a reduced exposure of personnel to radiation and shorter duration of confinement to bed. Patient survival rate was dependent mainly on parameters of tumour burden (FIGO stage), i.v. pyelogram or CT scan of paraaortic lymph nodes. On the other hand, neither the histological classification as epidermoid or adenocarcinoma nor the WHO grading, were useful predictors of patient outcome.

[Prognostically relevant factors in malignant mixed Müllerian tumor]. / Prognostisch relevante Faktoren beim malignen Müllerschen Mischtumor.

In a retrospective analysis of 429 endometrial carcinoma and 29 malignant mixed Müllerian tumour (MMMT) patients, the prognostic factors were evaluated. More than 80% of endometrial carcinomata were staged as I or II, whereas about 30% of MMMT's already in stage III or IV (p less than 0.05). MMMT patients were 10 years older than the carcinoma group (73a vs 63a; p less than 0.001). The risk factors parity, adipositas, and diabetes were equally distributed in the two groups, the survival was worse in MMMT (p less than 0.0001). Applying univariate analysis stage, grading, myometrial invasion and type of therapy significantly affected the survival of endometrial carcinoma patients. After a Cox regression, only stage and grading remained significantly associated with the prognosis. For MMMT's, the survival was also influenced by stage, myometrial invasion, and kind of therapy. Moreover, the parity was found to affect markedly the course of disease. Cox regression of our data excluded all but stage and parity. The beneficial influence of parity on the prognosis of MMMTs, despite a latency of more than 20 years from the last birth to tumour appearance, is unique in oncology.

Urinary neopterin excretion in patients with uterine sarcomas.

Neopterin, a pyrazinopyrimidine compound, is a marker of activation of cell-mediated immunity. Urinary neopterin concentrations were measured in a total of 44 patients with uterine sarcomas. Pretherapeutic neopterin excretions were elevated in 78% (14/18). The mean neopterin concentration of patients with sarcomas was significantly higher (P less than 0.0001) than that obtained in women with benign myomas and healthy controls. Furthermore, a significant correlation of normal or raised neopterin concentrations with the clinical course of disease was found. These data suggest that urinary neopterin measurement might be a useful immunologic marker for women with uterine sarcomas.

[Modulation of hCG synthesis by alpha tumor necrosis factor in JAR choriocarcinoma cells]. / Die Modulation der hCG-Synthese durch Tumornekrosefaktor-Alpha bei JAR-Chorionkarzinomzellen.

The tumour necrosis factor (TNF) stimulates in cultured JAR choriocarcinoma cells the biosynthesis of hCG, including the free alpha and beta chain and the holo-hCG. Although elevated serum TNF levels have been shown by Balkwill et al. (1987) in about 50% of tumour patients, we were unable to confirm these data in the 10 examined patients, who had a choriocarcinoma. Despite its excellent in-vitro action, INF could not be confirmed to exercise an influence on the regulation of hCG in choriocarcinoma patients.

[The intraperitoneal installation of gamma interferon for the treatment of refractory ovarian carcinoma]. / Die intraperitoneale Instillation von Interferon-gamma zur Behandlung des refraktären Ovarialkarzinoms.

Patients with refractory ovarian cancer were treated intra-peritoneally with interferon-gamma. The maximum tolerated dose was achieved at 2 mg/m2. The substance was administered 3 times per week every second week. Interferon-gamma treatment activated locally the macrophages and induced a rise in neopterin urine, serum, and ascites levels. The tumor marker CA-125 showed marked fluctuations of more than 100% during interferon treatment and this was not correlated with neopterin. A flu-like syndrome and especially fatigue were the dose limiting side effects. Two of 3 evaluable patients died on tumor progression whereas one is now 18 months clinically free of disease.

Effects of interferon-alpha on macrophage activation in patients with ovarian carcinoma and cervical dysplasia.

Patients with progressive ovarian carcinoma and patients with dysplasia of the uterine cervix were studied in order to compare clinical efficacy, hematological toxicity and effects on macrophage activation of administered interferon-alpha for both patient groups. One of three patients with ovarian carcinoma showed a minor response. Four of six patients with cervical dysplasia had slight improvements of PAP-smears. Moderate hematological toxicity was observed in the former patient group while side effects were much more pronounced in the latter patients group. However, changes of hematological parameters were not statistically different. Interestingly, the administered interferon-alpha caused the same activation of macrophages in both patients groups as indicated by raised neopterin levels. This activation does not result in clinical improvement but appears to play a role for the hematological toxicity observed during therapy of patients with ovarian carcinoma. It has been suggested that suppression of hematopoiesis is mediated by interferon-gamma. The present neopterin data propose that this lymphokine is continuously produced through influence of the tumor and enhanced by interferon-alpha.

[Multiple cancers in gynecologic oncology]. / Mehrfachkarzinome in der gynäkologischen Onkologie.

An analysis of 97 patients with multiple primary gynaecological neoplasms (90 double-, 6 triple- and 1 quadruple carcinomas) was done at the Gynaecological Department of the University of Innsbruck. Two thirds of the tumour combinations were located in the female genital tract including the breast. Concerning the early detection of simultaneous or subsequent malignancies of the cervix or corpus uteri, one should pay attention to the mamma being involved in the treatment or aftercare of such cancers. In the same way the inner female genital tract has to be observed in breast cancer patients. Regular colposcopic and cytological examinations of the cervical portio as well as a systematic prevention of endometrial cancer (pistolet in local anaesthesia) is highly recommended. The prognosis of the "highly malignant" tumour does not worsen as a result of a second malignant cancer.

Preactivated T cells in cancer patients with poor prognosis.

We investigated the outcome of disease in correlation with pretherapeutic urinary neopterin levels in 161 patients suffering from cervical carcinoma and 51 patients suffering from ovarian cancer. Neopterin is produced by human macrophages upon stimulation with interferon gamma and is therefore a measure for activated T cells. In both types of cancer, neopterin levels before therapy were of predictive significance. Patients with pretherapeutically high neopterin levels were more likely to die earlier. Even 12-18 months after the start of therapy this effect was significant. The data indicate that primary events in the immune surveillance are intact in those patients but effector mechanisms might be diminished. Persistent activation of cell-mediated immunity appears to be unfavorable in cancer patients.

Urinary diversion in gynecologic malignancies.

A variety of methods for urinary diversion are employed in patients with gynecologic malignancies depending on whether there is an obstruction or fistula formation due to either tumor growth or radiotherapeutic injury. Percutaneous nephrostomy (PCN) has a low complication rate and is a good method for palliative urinary diversion or may precede some form of permanent diversion to restore the kidney function first. Indication for palliative diversion in tumor obstruction depends on many individual factors. A relative contraindication is tumor progression during therapy. 6-month survival was about 70% in patients with previously untreated tumors or recurrences. This rate is far better than reported in earlier studies, so that a palliative diversion has to be considered for these patients. Also a high rate of recanalization after therapy could be observed in the untreated group, allowing the PCN to be removed. However, this has not been shown to be a prognostic factor. In the individual patient some other aspects, such as quality of life and social status, have to be taken into account before a final decision can be made. Ureteral obstruction after radiotherapy is a rare finding and often mistaken for a more likely recurrence. Different methods to restore the urinary tract, such as reimplantation of the ureter, should be used as a first choice. When the stenosis is due to radiocystitis, enterocytoplasty will often be indicated. Diversion has then to be omitted. The poor quality of life because of permanent incontinence due to fistula formation makes diversion mandatory even if life expectancy is very short. Surgical closure of a large radiogenic fistula is rarely successful. In this situation, ileal conduit has proven its efficacy for long-term urinary diversion.

Combination chemotherapy with epirubicin and cisplatin in ovarian carcinoma.

Combination chemotherapy with epirubicin-cisplatin was employed after surgical treatment in 67 women with ovarian carcinoma. 50 mg/m2 of epirubicin and cisplatin each were administered at monthly intervals. The response rate was correlated with the clinical stage and the residual disease. Tumor regression (CR + PR) was observed in 63.6% of patients with stage III disease, and in 50% of those with stage IV disease. Furthermore, complete or partial responses were obtained in 86.4% of patients with a residual deposit of 2-5 cm, and in 33.3% of women with a residual deposit exceeding 5 cm in diameter. Anemia occurred in 47.8%, leukopenia in 43.3%, and thrombocytopenia in 4.5% of the patients. No cardiotoxicity was recorded.

Safe use of propofol in a patient with acute intermittent porphyria.

On two occasions a patient suffering from acute intermittent porphyria (AIP) was anaesthetized with propofol as the sole agent. The concentrations of urinary porphobilinogen, porphyrins and porphyrin precursors did not exceed preoperative values, and no exacerbation of the disease was noted.

[Rectal shielding for a Selectron-ring applicator system (HDR- and LDR-afterloading)]. / Rektumabschirmung für ein Selectron-Ringapplikator-System (HDR- und LDR-Afterloading).

In order to decrease the morbidity rate after combined radiotherapy of the cervix carcinoma, a tungsten shield 3 and 5 mm thick for the rectum has been developed by the authors which is applied with the ring and pin applicator of the Selectron unit (LDR- and HDR-afterloading). The isodose curves were measured in a plexiglas phantom, and the radiation dose at the reference points was determined by means of a ionization dosimeter. The phantom measurements were performed with the same arrangement of sources as applied in radiotherapy. The measurements showed a dose reduction at point Rmax of 33% (HDR) and 44% (LDR) with the tungsten shield 5 mm thick.