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Purpose: Efficacy of MEK inhibitors in KRAS+ NSCLC may differ based on specific KRAS mutations and comutations. Our hypothesis was that docetaxel and trametinib would improve activity in KRAS+ NSCLC and specifically in KRAS G12C NSCLC., Patients and Methods: S1507 is a single-arm phase II study assessing the response rate (RR) with docetaxel plus trametinib in recurrent KRAS+ NSCLC and secondarily in the G12C subset. The accrual goal was 45 eligible patients, with at least 25 with G12C mutation. The design was two-stage design to rule out a 17% RR, within the overall population at the one-sided 3% level and within the G12C subset at the 5% level., Results: Between July 18, 2016, and March 15, 2018, 60 patients were enrolled with 53 eligible and 18 eligible in the G12C cohort. The RR was 34% [95% confidence interval (CI), 22-48] overall and 28% (95% CI, 10-53) in G12C. Median PFS and OS were 4.1 and 3.3 months and 10.9 and 8.8 months, overall and in the subset, respectively. Common toxicities were fatigue, diarrhea, nausea, rash, anemia, mucositis, and neutropenia. Among 26 patients with known status for TP53 (10+ve) and STK11 (5+ve), OS (HR, 2.85; 95% CI, 1.16-7.01), and RR (0% vs. 56%, P = 0.004) were worse in patients with TP53 mutated versus wild-type cancers., Conclusions: RRs were significantly improved in the overall population. Contrary to preclinical studies, the combination showed no improvement in efficacy in G12C patients. Comutations may influence therapeutic efficacy of KRAS directed therapies and are worthy of further evaluation. See related commentary by Cantor and Aggarwal, p. 3563., (©2023 American Association for Cancer Research.)

Importance: Erlotinib is a standard first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Median progression-free survival (PFS) with erlotinib is approximately 10 months., Objective: To determine whether adding bevacizumab to erlotinib treatment results in superior progression-free survival compared with erlotinib alone., Design, Setting, and Participants: This phase 2 randomized clinical trial compared erlotinib plus bevacizumab with erlotinib alone in EGFR-mutant NSCLC. The trial was conducted in 17 US academic and community medical centers among 88 patients with EGFR exon 19 deletion or exon 21 L858R mutation based on local testing and stage 4 NSCLC who were eligible for bevacizumab. Patients were enrolled between November 2, 2012, and August 22, 2016, and followed up for a median (range) of 33 (0.7-62.5) months. Data were analyzed on August 28, 2018, and included data from November 2, 2012, to August 20, 2018., Interventions: Patients were randomized with equal allocation to 150 mg of oral erlotinib daily alone or with 15 mg/kg of intravenous bevacizumab every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent., Main Outcomes and Measures: The primary outcome was PFS as assessed by the investigator; secondary outcomes were objective response rate (ORR), adverse events, and overall survival (OS). Analysis was designed to detect a hazard ratio (HR) of 0.667 for PFS (an improvement from a median PFS of 10 to 15 months)., Results: Among 88 patients enrolled, the median (range) age was 63 (31-84) years; 62 patients (70%) were female; 75 (85%) were white, 8 (9%) were African American, 3 (3%) were Asian, and for 2 (2%), data on race were not available. Forty-eight patients (55%) were never smokers, 45 patients (51%) were of Eastern Cooperative Oncology Group performance status 1, and 59 patients (67%) had EGFR exon 19 deletion. Compared with erlotinib, the combination did not result in a significant difference in PFS (HR, 0.81; 95% CI, 0.50-1.31; P = .39; median PFS 17.9 [combination] and 13.5 months [erlotinib]), ORR (81% vs 83%; P = .81), and OS (HR, 1.41; 95% CI, 0.71-2.81; P = .33; median OS, 32.4 months [combination] and 50.6 months [erlotinib]). Adverse events of grade 3 or higher observed in 5 or more patients in the combination and erlotinib arms were skin eruption in 11 (26%) vs 7 (16%) patients, diarrhea in 4 (9%) vs 6 (13%) patients, hypertension in 17 (40%) vs 9 (20%) patients, and proteinuria in 5 (12%) vs 0 (0%) patients., Conclusions and Relevance: Erlotinib plus bevacizumab compared with erlotinib did not result in a significant improvement in PFS in EGFR-mutant NSCLC., Trial Registration: ClinicalTrials.gov identifier: NCT01532089.

Background: Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC., Methods: This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954., Findings: Between Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the primary analysis (erlotinib [n=38], cabozantinib [n=38], erlotinib plus cabozantinib [n=35]). Compared with erlotinib alone (median 1·8 months [95% CI 1·7-2·2]), progression-free survival was significantly improved in the cabozantinib group (4·3 months [3·6-7·4]; hazard ratio [HR] 0·39, 80% CI 0·27-0·55; one-sided p=0·0003) and in the erlotinib plus cabozantinib group (4·7 months [2·4-7·4]; HR 0·37, 0·25-0·53; one-sided p=0·0003). Among participants included in the safety analysis of the erlotinib (n=40), cabozantinib (n=40), and erlotinib plus cabozantinib (n=39) groups, the most common grade 3 or 4 adverse events were diarrhoea (three [8%] cases in the erlotinib group vs three [8%] in the cabozantinib group vs 11 [28%] in the erlotinib plus cabozantinib group), hypertension (none vs ten [25%] vs one [3%]), fatigue (five [13%] vs six [15%] vs six [15%]), oral mucositis (none vs four [10%] vs one [3%]), and thromboembolic event (none vs three [8%] vs two [5%]). One death due to respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug, and one death due to pneumonitis occurred in the erlotinib plus cabozantinib group, deemed related to either drug or the combination., Interpretation: Despite its small sample size, this trial showed that, in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone, with additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population., Funding: ECOG-ACRIN Cancer Research Group, National Cancer Institute of the National Institutes of Health., Competing Interests: Declaration of Interests Dr. Neal reports personal fees from Clovis, personal fees from CARET/Physicians Resource, grants and personal fees from Nektar, grants and personal fees from Boehringer Ingelheim, personal fees from ARMO BioSciences, grants from Genentech/Roche, grants from Merck, grants from ArQule, grants from Novartis, outside the submitted work. Dr. Dahlberg reports a patent PCT/US2014/054821 pending to Dana-Farber Cancer Institute. Dr. Wakelee reports personal fees from Peregrine, grants and personal fees from Helsinn, personal fees from ACEA, grants and personal fees from Pfizer, grants from BMS, grants from XCovery, grants from Celgene, grants and personal fees from Roche/Genentech, grants from AstraZeneca/MedImmune, personal fees from Lilly, grants from Gilead, grants from Clovis, grants from Pharmacyclics, grants from Exelixis, grants from Novartis, outside the submitted work. Dr. Carbone reports personal fees from Ariad, personal fees from AstraZeneca, personal fees from Bayer HealthCare, personal fees from Biothera, personal fees from Boehringer Ingelheim, grants and personal fees from Bristol Myers-Squibb, personal fees from Clovis Oncology, personal fees from Genentech/Roche, personal fees from Guardant Health, personal fees from Inivata, personal fees from Janssen Diagnostics, personal fees from Merck, personal fees from Novartis, personal fees from Peregrine Pharmaceuticals, personal fees from Synta Pharmaceuticals, personal fees from Teva Pharmaceuticals, outside the submitted work. Dr. Lerner reports grant from Acerta Pharma, grant from Amgen, grant from Bayer HealthCare Pharmaceuticals Inc., grant from Celcuity, LLC, grant from Cephalon, Inc., grant from Teva Branded Pharmaceutical Products R&D, Inc., grant from Janssen Research and Development, LLC, grant from Pfizer, grant from Roche/Genentech, Inc., outside the submitted work. Dr. Ramalingam reports personal fees from Amgen, AstraZeneca, Abbvie, BMS, Lilly, Celgene, Genentech, and Novartis outside the submitted work. The other authors declared no conflicts of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cigarette smoking exerts a carcinogenous effect in various organs, either by direct contact or by distant nocivity. The authors present a survey of literature dealing with the effect of cigarette smoking on the female genital tract. The respective data show clearly that cigarette smoking may induce carcinoma of the cervix, whereas no significant correlation between cigarette smoking and carcinoma of the uterus can be established. Epidemiologic, etiologic and pathogenetic aspects of cigarette smoking and its influence on the genital tract are presented and discussed.

The incidence and mortality rate from breast cancer in Austria from 1983 to 1987 were obtained from data of the Austrian Cancer Register. There were on average 3012 new cases per year (75.8 per 100,000 women). Age-standardized incidence (European standard population) as calculated by the WHO was 64.1 per 100,000. Distribution by stages ("US end-result group") showed stage I (localized) in 44.7%, stage II (spread to immediate neighbouring structures and regional lymph nodes) in 41.3% and stage III (generalized) in 14%. There was no significant difference between the various age groups regarding stage distribution. The number of deaths increased from 1,462 in 1983 to 1,675 in 1987, a raw mortality rate of 36.8 and 42.2, respectively. Age-standardized mortality increased from 29.0 to 31.2, respectively. These data point to a further increase in incidence and mortality rate from breast cancer in Austria.

Case report on a severe cardial malformation associated with trisomia 21, diagnosed by ultrasound-screening in the 34th week of gestation. Further diagnostic evaluation of the case and therapeutic management are described. The problems of modern malformation diagnostics by routine ultrasound scanning in pregnancy are discussed.

The ability of an antibiotic to penetrate into the extravascular site of infection is particularly important for a successful perioperative antibiotic prophylaxis and postoperative therapy of bacterial infection. We, therefore, measured interstitial fluid concentrations of ceftriaxone in the subperitoneal space following hysterectomy using Rubinstein's disc method after intravenous administration of 1 g of ceftriaxone preoperatively. After removal of the uterus, two disc units were implanted intraoperatively in the right and left subperitoneal space of 16 patients and were drawn out through the open vaginal cuff after given periods of time. Five disc and blood specimens were obtained after 90 min and 2, 6, 12, 24, and 48 h, respectively. Ceftriaxone concentrations were determined by bioassay. After administration of 1 g of ceftriaxone, interstitial fluid concentrations following hysterectomy were above the MIC90 of most pathogens encountered in gynecologic infections over a period of 24 h.

A prospective, randomized clinical trial was conducted to compare the efficacy and tolerance of a single dose of 1 g ceftriaxone i.v. daily with 3 doses of 1 g cefotaxime i.v. daily for obstetric and gynecologic infections. Both agents are characterized by a wide spectrum and potent activity. Furthermore, ceftriaxone has an outstanding serum half-life of 8 h. 41 patients with pelvic inflammatory disease, pelvic or wound infections after vaginal or abdominal hysterectomy, endomyometritis and urinary-tract infection were included. Patients were monitored clinically by routine laboratory methods (erythrocyte sedimentation rate, white blood cell count and cross-reacting protein) and bacteriologically. Clinical parameters of infection were fever, local pain and/or tenderness, a sactosalpinx or pyosalpinx at palpation and cervical secretion. Clinical cure was achieved in 77.3% in the ceftriaxone and in 78.9% in the cefotaxime group, improvement in 3 (13.6%) and 4 patients (21.0%), respectively. 2 clinical failures were seen in the ceftriaxone group. One was a severe pelvic infection following vaginal hysterectomy, which responded to the addition of metronidazole, the other was due to a chlamydial salpingitis, which was cured with a 10-day course of doxycycline. Both antibiotics were well tolerated. Our results suggest that for obstetric and gynecologic infections a single 1-gram dose of ceftriaxone is equally effective as three 1-gram doses of cefotaxime.

In a prospective clinical and bacteriological study the endocervical and endometrial flora of 38 patients with biopsy proven cancer of the endometrium was studied before and after intrauterine irradiation with 10 Gy (Ir-192, afterloading device, Buchler, Braunschweig). Bacteriological swabs were taken transcervically. Anaerobic transport media were used and cultures were done aerobically and anaerobically. The mean number of aerobic organisms per patient increased from 2.13 to 2.49 (not significant (n.s.)), and of anerobic organisms from 1.42 to 2.00 (n.s). Neither the recovery rate of aerobic and anaerobic bacteria nor the composition of endometrial flora was altered significantly by intracavitary irradiation. Only aerobic sporeformers increased from 5.3% to 21% (2 p less than 0.05). The most prevalent aerobic species were S. epidermidis, streptococci and E. coli, the predominant anaerobic species Pepto- and Peptostreptococcus and Bacteroides. Our results clearly show that the intrauterine administration of 10 Gy by a Ir-192-afterloading device does not sterilize the endocervix or endometrium and infections may occur after intracavitary radiotherapy.

Bilateral adnexal masses in an 18-year old turkish girl were diagnosed as Burkitt's lymphoma. Aetiology, diagnosis and therapy (surgery and chemotherapy) of this by gynecologists rarely seen disease are presented.

Sixty-two patients with primary carcinoma of the female urethra were treated with a combined radiation therapy (high-dose intracavitary vaginal radium and external beam). Treatment was strictly individualized, but an administered tumor dose of 5500-7000 rad (55-70 Gy) was always attempted. Forty-two patients (67.7%) had tumors of the anterior urethra, and in 20 women (32.3%) the posterior urethra was involved. In 19 patients (30.6%) the clinical diagnosis of lymph node involvement was made. The overall 5-year-survival rate was 64.5%. Patients with anterior urethral carcinoma had a higher 5-year-survival rate (71.4%) than patients with posterior carcinoma (50.0%). The favorable results underline the substantial role of radiation therapy for this malignancy.

An anonymous expert inquiry was carried out during the First Annual Meeting of the Austrian Society for Senology in Vienna in December 1984. To 230 participants - all of them experts in the fields of gynaecology, surgery, radiology and internal medicine - a semi-structurised inquiry form was handed out, questioning for actual problems of routine screening mammography and efficacy of breast self-examination. Only 27 persons (12%) returned the completely filled out inquiry form, 14 experts (52%) advocated a mass-screening with the legal health examinations, most of them from the 30th year of age on in intervals of two years, 17 doctors (63%) agreed with the screening of well defined risk groups with individually determined screening intervals, most of them also from the 30th year of age on. 17 colleagues (63%) rather preferred a screening consisting of basis-mammography with individualised, according to age and personal risk factors adjusted screening intervals, again mostly from the 30th year of age on. Thus our study suggests no particular expert preference of a certain screening modality. 22 experts (81%) believe that breast self-examination from the 20th year of age on is of value, half of them recommending monthly controls. These doctors also believe that one should inform women about this early detection method through directed campaigns in the mass media. A representative inquiry among 1,000 Austrian women, carried out from the fund "Kampf dem Krebs" during summer 1986, showed that, although 70% are informed about the possibility and importance of early detection of breast cancer as well as of the method of breast self-examination, only about 14% perform it indeed regularly.

In the past decade modern, perioperative short-term antibiotic-prophylaxis has been widely accepted in certain gynecological operations and in caesarean section. Many studies demonstrate the clinical effectiveness. Well established indications are vaginal hysterectomy and high risk caesarean section with a high rate of infections. The infectious morbidity should be carefully evaluated at every department. The older Cephalosporins (first and second generation) should be used for prophylaxis.

A representative inquiry was carried out among 100 Austrian gynecologists and obstetricians. Aim of the study was to determine the percentage of gynecologists, who carry out routinely the palpation of the breast in their office: 73% of all gynecologists are performing breast-palpation routinely in every patient, 27% only in case of complaints. The highest percentage of routine-breast-palpation performing gynecologists was found among doctors, who are in private-practice only (97%). Particularly low percentages, however, were found e. g. among doctors, who have contracts with all social insurances (58%), who have a high frequency of social-insured patients (55%) or have many patients per day (61%). Since the routine-breast-palpation is of particular importance for the reduction of breast cancer mortality, this examination should be also performed routinely by all general practitioners, internists and surgeons. Therefore, from the point of view of preventive medicine and public health the routine examination of the female breast should be refunded by social insurance in Austria.

In a prospective pharmacokinetic study the serum and tissue concentrations of ciprofloxacin (Bay O9867), a new carboxyquinolone antimicrobial agent were studied. 22 patients were given 300 mg ciprofloxacin i. v. before the operation (group A), and 19 patients were premedicated with 500 mg ciprofloxacin orally twice daily for three days followed by 300 mg i. v. preoperatively. Tissue samples weighing approximately 2 g were taken from the fallopian tubes, the ovaries, the fundus myometrium and the cervix. Ciprofloxacin concentrations were measured biologically by the cup plate agar diffusion method. Ciprofloxacin concentrations in serum and gynecological tissues were within the same range in both groups. Maximal serum concentrations of 6 and 4 mg/l, respectively, were recorded immediately after infusion. After 2 h serum concentrations ranged from 0.6 to 1.3 mg/l in both groups. At the same time, the tissue concentrations ranged from 0.62 to 3.3 mg/kg, indicating that tissue levels exceed corresponding serum concentrations. On average ciprofloxacin is concentrated in the extravascular space two-fold, as compared to the corresponding serum concentrations. There is no drug accumulation. The tissue concentrations obtained provide a full antibacterial coverage for gynecological infections, since the MIC for the most pathogenic bacteria is less than 1 mg/l.

In a prospective clinical and microbiological study covering 67 prepubertal children the vaginal flora of 31 asymptomatic children was compared to 36 children suffering from abnormal vaginal discharge and/or vulvovaginitis. Vaginoscopy was employed to obtain bacteriological specimens without contamination. Swabs were inoculated into prereduced transportmedia (PORT A CUL, BBL) and cultured aerobically and anaerobically. The most prevalent aerobic organisms were Staphylococcus epidermidis. Enterococci and Escherichia coli; the predominant anaerobic bacteria were Peptococcus and Peptostreptococcus, Veillonella parvula, Eubacteria, Propionibacterium and Bacteroides species. A similar microbiological pattern was found in both groups, although anaerobes, like Peptococci and Peptostreptococci and Bacteroides species, as well as yeasts, like Candida albicans were significantly more frequent in the group with signs and symptoms. Lactobacilli were less common in this group.

A prospective, randomized, controlled comparative clinical trial was conducted to assess the efficacy and tolerability of 2 regimens of amoxicillin. In group A a single dose of 3 g amoxicillin and in group B a 4-day course of 3 doses of 750 mg amoxicillin tablets were administered 8-hourly. Significant bacteriuria (greater than or equal to 10(5) cfu/ml midstream urine) and of urine samples obtained by bladder catheterization (greater than or equal to 10(4) cfu/ml) was diagnosed with the dip-slide method (Uricult). 91 pregnant women with a mean gestational age of 25 weeks (14-38) were randomly allocated to both treatment groups. Group A consisted of 53 patients, group B of 38. The treatment groups were comparable in terms of age, duration of pregnancy and additional therapy. Control examinations of urine cultures were taken after 1 and 4 weeks following therapy. The predominant bacterial species was E. coli isolated in 60 to 65 percent. Bacteriological cure rates at 1 and 4 weeks were in group A 77% and 74% and in group B 62% each respectively. The differences in cure rates were not significant. Side effects occurred in group A in 4% and in group B in 13%. Our results suggest that for the treatment of asymptomatic bacteriuria in pregnancy a single dose of 3 g of amoxicillin is equally effective and acceptable as a 4-day course with the advantage of a lower total-dose, lower costs and a better compliance.

With regard to discussions in the public being held in this country throughout the past months, a representative inquiry was carried out among Austrian gynaecologists and obstetricians. Aim of the study was to determine the percentage of obstetricians performing the so-called "birth without violence" according to Leboyer as well as their opinion to this alternative obstetrical thinking: Approximately one half of Austrian gynaecologists is carrying out so-called "births without violence." However, the vast majority of them (78%) prefers for their own wives and their own children "electronic fetal monitoring" during labour and delivery. Analysis of our data according to the age of the doctor, the geographic region of his office, and the number of treated patients shows a considerable discrepancy between performance and personal preference of "alternative" obstetrical methods. These results should be taken into account for further discussions in the public about "births without violence", as obstetricians are among all professions those experts who can estimate the risks of pregnancy and delivery best.

A prospective, randomized, controlled comparative clinical trial was carried out with the aim of investigating the efficacy and tolerance of two different dosage regimens of amoxicillin in the treatment of asymptomatic bacteriuria during pregnancy. Patients in group A received a single dose of 3 g amoxicillin, which was compared to a 4-day course of 3 X 750 mg amoxicillin tablets taken every 8 h (group B). Significant bacteriuria (CFU greater than or equal to 10(5)/ml clean catch midstream urine and CFU greater than or equal to 10(4)/ml urine obtained by bladder catheterization) was diagnosed using the dip-slide method (Uricult). 91 pregnant women with a mean gestational age of 25 weeks (14-38) were randomly allocated to the two treatment groups. 53 patients were assigned to group A and 38 patients to group B. The treatment groups were comparable in terms of age and duration of pregnancy. Urine culture tests were performed 1 and 4 weeks after completion of therapy. The predominant species was Escherichia coli, which was isolated in 60-65% of the cases. Bacteriological cure rates at 1 and 4 weeks, respectively, were 77 and 74% in group A, and 62 and 62% in group B. These differences were statistically not significant. The incidence of side effects was 4% in group A and 13% in group B. The results obtained in the present study suggest that in the treatment of asymptomatic bacteriuria in pregnancy, a single dose of 3 g amoxicillin is as effective and acceptable as a 4-day course. In addition, the single-dose regimen offers the advantage of a reduction in total dose, lower costs and better patient compliance.

Infections in patients with gynecologic malignancies occur frequently and are the cause of death in 50 to 60% of the cases. The patient with cancer is a compromised host with an increased susceptibility to infection due to the malignancy itself on the one hand and due to therapeutic-modalities, like extensive surgical procedures, radiation- and cytotoxic chemotherapy on the other hand. Aetiologically these infections are mostly due to a disruption of anatomic structures which normally prevent the invasion of exogenous or endogenous microorganisms, or to obstructive processes or to tumour necrosis. Septicaemia can result from propagation of such a localized infection beyond the site of the tumour. The causative pathogens infecting the compromised host are mostly members of the indigenous microbial flora of the genital tract, which is influenced by surgery, irradiation and chemotherapy. Postoperatively in the vaginal vault the number of most potentially pathogenic aerobic and anaerobic bacterial species is higher, polymicrobial mixed infections are frequent. Neither the intracavitary radiation-therapy with Radium or Iridium-192 (afterloading) nor the external high-voltage therapy decrease the number of pathogenic bacterial species in the uterus and in the vagina of patients with cervical or endometrial cancer. The symptoms of infection in cancer patients can be "masked". Fever in patients with genital malignancies is mostly due to local infections and influences the prognosis negatively. The 5-year survival rate of irradiated patients with fever is significantly lower. Infections following radical hysterectomy, irradiation and/or cytotoxic chemotherapy like pelvic abscesses, peritonitis, pneumonia and septicaemia can be fatal. Urinary-tract-, wound- and vaginal vault-infections occur frequently, but are rarely severe. Therapeutically in severe infections a combination antibiotic therapy, which is effective against most pathogenic members of the genital flora, is required. Short courses of perioperative prophylactic antibiotics are useful both in radical hysterectomy and with intracavitary irradiation.

Several new aspects of lactation are summarized and concerning the current pattern of breast-feeding in the region of Vienna, including the results of recent studies, carried out at the Ith Department of Obstetrics and Gynecology of the University of Vienna are discussed. Newer theoretical data of the physiology of lactation, in particular the action of prolactin and its inhibition are reviewed. A detailed survey of the advantage of the natural nutrition of the infant with the mother's milk, and the problem "breast-feeding and drugs", is given. The author also presents a new approach in the treatment of postpartal breast-engorgement, purpureal mastitis and primary and secondary inhibition of lactation with bromocriptine.

The influence of radiation therapy on cell-mediated immune reactions in cancer patients seems to depend on source, dose, and area of irradiation, as well as on the variables reflected by the patient population investigated. In the present study we demonstrated that brachytherapy (192Ir afterloading), applied to patients with inoperable stage I endometrial cancer, has no immediate or sustained effect on lymphocyte function. Both lymphocyte mitogen response and natural killer cell (NK) activity are not significantly changed in terms of baseline values compared with test results during and after therapy. Brachytherapy, as used in this study, has no influence on cell-mediated immunity in patients with endometrial cancer stage I.

Forty cases of antepartum fetal death occurring among 6668 deliveries at the Ist Department of Obstetrics and Gynecology of the University of Vienna between 1976 and 1979 were evaluated. The fetal death rate was 6 per 1000 births. In 32 cases (80%) a diagnosis identifying the disorder, that initiated the cause of fetal death, could be established. The remaining 20% did not have a demonstrable diagnosis. The most frequent cause of death in this series was in 40% severe toxemia of pregnancy causing a chronic nutritive placental insufficiency. Histologically in such cases regressive changes of the placenta, such as microinfarcts, necrosis and deposition of intervillous fibrin were found. Rarer causes, also associated with intrauterine asphyxia were 2 cases each of placenta praevia (5%), and abruption placentae (5%), one cord accident (2.5%) and one case of postmaturity (2.5%). The second most important etiological factor was in 12.5% the ascending intrauterine infection prior or after the premature rupture of the fetal membranes. Bacteriologically the most common organisms isolated were E. coli, enterococci and anaerobic bacteria. One fetal death was due to rhesus incompatibility, and in one case both twins died in utero (2.5%). Our results suggest, than an early diagnosis and a successful treatment of placental insufficiency would permit a further reduction of the perinatal mortality rate. In conclusion the absolute necessity of the performance of all available diagnostic means in order to prevent recurrence of a stillbirth is emphasized.

Ultrasonically guided, percutaneous fine-needle aspiration biopsy allows final histological and/or cytological diagnosis in patients with benign or malignant space-occupying growths even of small size. Therapeutic puncture and drainage of postoperative abdominal or retroperitoneal growths (haematoma, seroma, lymph cyst, abscess) however, requires 1.) dilatation of the percutaneously established puncture channel and 2.) continuous vacuum aspiration over a period of several days or weeks. We report on three therapeutic punctures in two patients with retroperitoneal lymph cysts following abdominal radical hysterectomy with lymphonodectomy and one patient with abscess formation following nephrectomy. The technique employed was as used in percutaneous nephrostomy. Under local anaesthesia and permanent ultrasound guidance the lesion is punctured with a 1.3 mm hollow puncture needle of three parts (Angiomed) and after aspiration of fluid a 0.9 mm wire guide with a curved, soft tap was inserted through the puncture needle in the lesion. The puncture channel is then dilated under x-ray visualisation with a Teflon-coated fasciadilatator (Cook) to Charr. 16 (20). Finally either a polyvinyl catheter with two lateral apertures (Cook) or a double-barrelled Shirley Drain is inserted and fixed to the skin with a stitch. For diversion a closed system is used. Over a period of one to two weeks 50 to 200 millilitres of secretion are drained off per day in decreasing quantity. The patients returned to normal temperature and recovered entirely. The advantage of our method is the avoidance of dangerous and difficult secondary surgery.