Prothrombin fragment F 1 + 2 plasma concentrations in patients with gynecologic malignancies.

Malignant diseases have been shown to cause hypercoagulable states. Elevated prothrombin fragment F 1 + 2 plasma levels occur, when prothrombin is converted into thrombin by factor Xa. In order to evaluate the role of prothrombin fragment F 1 + 2 as an indicator for hemostatic disorders in patients with gynecologic malignancies, plasma levels of 76 patients with various malignancies of the female genital tract and those of 25 healthy subjects were investigated. Fifty-two of 76 (68.4%) patients with malignant diseases showed elevated F 1 + 2 plasma concentrations, whereas no elevated plasma levels were observed in the control group. Mean values of F 1 + 2 in the study group and the controls were 1.94 +/- 1.63 and 0.89 +/- 0.07 nmol/liter, respectively (P < 0.01). These results provide further evidence that gynecologic malignancies can induce hypercoagulable states.

[Human papillomavirus infection of the uterine cervix in immune suppressed women after kidney transplantation]. / Humane Papillomavirus-Infektion der Cervix uteri bei immunsupprimierten Frauen nach Nierentransplantation.

In 23 women, who had immunosuppressive therapy following renal transplantation, routine cytology and colposcopy were performed. Colposcopically directed punch biopsies were taken from the most suspect area. If no pathologic finding was evident during colposcopy a random sample was taken from the transformation zone. Histology revealed condylomatous lesions in seven cases. In two of the lesions, a CIN II was detected. To each woman with a renal allograft and therefore immunosuppressive therapy, two cases were matched for age, parity, and histological finding as a control group. Human papillomavirus (HPV) detection was performed by in-situ hybridisation. HPV infection rate in women with renal allografts was higher in biopsy specimens with condylomatous lesion (86%), as well as in tissue without condylomatous lesions (25%), compared to controls (56% and 9%). The high prevalence of cervical dysplasia and high HPV infection rate in women with immunosuppressive therapy, indicates the need for accurate and regular cytologic and colposcopic examinations in these patients.

[Malignant lymphomas of the vulva and vagina]. / Maligne Lymphome an Vulva und Vagina.

Primary appearance of a malignant lymphoma in the vulvovaginal region is extremely rare. In this paper, we report on three such cases we observed during the last few years. There was no difference in clinical manifestation compared to cancer of the vulva/vagina. The diagnosis was made using histological and immunohistochemical methods. Choice of the treatment depended upon the stage of malignancy and spreading of the tumourous changes (radiation, chemotherapy). On reviewing the literature of the last 15 years, we could not find any description of primary malignant lymphoma in the vulva and vaginal region.

Squamous cell carcinoma antigen, tumor associated trypsin inhibitor and tissue polypeptide specific antigen in follow up of stage III cervical cancer.

189 clinical and serological examinations were performed in 30 patients before treatment and during follow up of squamous cell cervical cancer stage FIGO III. The serum levels of the tumor markers squamous cell carcinoma antigen (SCC), tumor associated trypsin inhibitor (TATI) and tissue polypeptide specific antigen (TPS) were determined. Sensitivity/specificity for SCC was 63%/91%, TATI 54%/74%, TPS 59%/86% and for a combination of SCC and TPS 81%/77%. In 14 women with recurrence of disease SCC showed lead time effects in seven patients in a time range from three to nine months. SCC was pre-therapeutically elevated in nine cases and showed lead time in five of them. Pretherapeutic TPS serum levels were elevated in seven cases. In all of them lead time effects appeared ranging from three to nine months. TPS never showed lead time effects in patients without elevated pretherapeutic levels. A combination of SCC and TPS in our material provided lead time in 10 of 14 cases.

Oral contraceptives and human papillomavirus infection in cervical intraepithelial neoplasia.

We report about 142 patients from whom colposcopically directed cervical punch biopsies were taken which showed condylomatous lesions with or without cervical intraepithelial neoplasia (CIN). Fifty-six (39.4%) of these women used oral contraceptives (OC) for at least two years before examination. We used DNA in situ hybridization on all biopsies for detection of human papillomavirus (HPV)-DNA. Among OC users a significant trend towards higher HPV infection rates in high grade CIN (odds ratio 2.9, P less than 0.05) was found, whereas non-users of oral contraceptives had the highest HPV infection rate in condylomatous lesions without CIN (odds ratio 0.5, P less than 0.05). Thus in OC users HPV infection was about 24 times more likely in CIN III as in condyloma, while among non-users the trend was the other way round (7-fold likelihood of HPV positivity in condyloma compared to CIN III). Other known risk factors for cervical carcinoma did not influence HPV infection rates in either group.

Cervical neoplasia and human papilloma virus infection in prostitutes.

OBJECTIVES: To evaluate the prevalence and incidence of PAP smears indicating cervical dysplasia as well as human papillomavirus (HPV) infection in prostitutes. DESIGN: Prevalence and incidence study of cervical dysplasia and HPV infection in prostitutes. For detection and typing of HPV-DNA In Situ Hybridisation (ISH) was performed in tissue samples with CIN gained by colposcopically directed punch biopsies. SETTING: Second Department of Obstetrics and Gynecology, University of Vienna Medical School and STD Clinic of the Public Health Office, Vienna. SUBJECTS: Registered prostitutes attending the STD Clinic of the Public Health Office and a control group. RESULTS: 978 prostitutes and 5493 women with unknown cytological anamnesis were compared. Frequency of positive PAP smears was significantly higher in prostitutes (6.13% versus 1.43%). To determine the pick-up rate of cervical dysplasia during one year after negative cytology we compared 722 prostitutes and 3162 controls. Prostitutes showed a significant higher dysplasia pick-up rate (3.05% to 1.07%) compared with controls. HPV detection rate in prostitutes was similar to that in the control group. The distribution of HPV types revealed a higher frequency of "high risk" HPV 16/18 and 31/33 in prostitutes. CONCLUSION: The results demonstrate a higher incidence and prevalence of cervical dysplasia in prostitutes and therefore suggest regular cervical PAP smear screening in registered prostitutes twice a year.

[Prognostic factors in stage Ia-IIb invasive cervix cancer after radical hysterectomy with special reference to stroma reaction]. / Prognosefaktoren beim invasiven Zervixkarzinom der Stadien Ia-IIb nach radikaler Hysterektomie unter besonderer Berücksichtigung der Stromareaktion.

158 cases of invasive carcinoma of the uterine cervix stages Ia to IIb were analysed with respect to the following prognostic criteria: histological stage, presence of nodal metastases, vascular space invasion and inflammatory stromal reaction at the periphery of the tumor. The assessment of these criteria was correlated to the prevalence of tumor recurrence. In cases with absent nodal metastases, a significant increase of tumor recurrence in stage IIb compared to other stages was noted. A constant increase of the recurrence rate was found, when nodal metastases were present, although the incidence of positive lymph nodes was approximately equal in stages Ic, IIa and IIb. The involvement of the parametrium therefore appears to be a significant parameter for the poor prognosis in stage IIb. Vascular space invasion proved to be a significant parameter with regard to lymph node involvement. When no vascular space invasion was obvious, 94% of the cases showed tumor-free lymph nodes. Overall, heavy inflammatory infiltration at the tumor periphery correlated with a good prognosis. In cases of heavy inflammatory stromal reaction, the risk of nodal metastases and tumor recurrence was significantly lower, independent of the histological stage. The incidence of heavy inflammatory infiltration was significantly higher in microinvasive carcinomas than in clinically invasive tumors. Therefore, the extent of inflammation appears to be an additional useful prognostic index to identify a group of patients at high risk for recurrence and reduced chance of survival.

[Mild cervix dysplasia: does diagnostic biopsy have a "therapeutic" effect?]. / Milde Zervixdysplasien: Hat die diagnostische Biopsie einen "therapeutischen" Effekt?

The aim of the study was, to evaluate the possible curative effect of punch biopsy on low grade cervical intraepithelial dysplasia (CIN I) as indicated by the literature. After a three-month interval, 115 women with PAP-smears indicating CIN I were subsequently controlled by cytologic cervical smears. Additional colposcopically directed punch biopsies were taken in 26 patients at the first examination. The remission rate was similar in patients with or without punch biopsy (54% to 49%), as well as the progression rate (8% to 7%). In addition we performed in-situ hybridisation in all biopsy specimens for the detection of human papillomavirus (HPV)-DNA. On comparing the progression and remission rate of women with HPV-positive and HPV-negative dysplastic tissue, we found no difference between these two groups. Punch biopsy does not seem to have a therapeutic effect either in HPV positive or HPV negative CIN I.

Trends in thirty years of vaginal hysterectomy.

Vaginal hysterectomy, as currently performed at the University of Vienna, was first described by Halban in 1932. From 1955 to 1985, a total of 9,967 hysterectomies were performed. The vaginal route was used for 6,078 (60.9 per cent) of these procedures. Sixty-four per cent of the women operated upon were multiparous, 27 per cent were uniparous and 8 per cent were nulliparous. A comparison of the periods 1955 to 1975 and 1976 to 1985 revealed the following trends: the incidence of uterine myomas (30.6 to 27.1 per cent), in situ carcinoma of the cervix (6.5 to 7.9 per cent) and endometrial carcinoma (1.4 to 0.6 per cent) remained largely constant. In the past decade, indications for positional abnormalities (uterine descent and prolapse) were encountered more often (27.6 to 41.6 per cent) than in the first observation period, while the incidence of recurrent metrorrhagia was found to decline (33.9 to 22.8 per cent). The most common complications included hemorrhage during the operation, lesions of the bladder, hemorrhage until 48 hours after surgical treatment and hemorrhage from days 2 to 14 postoperatively (around 0.5 per cent, respectively). During the second observation period, no postoperative fistulas developed. Two instances of tubal prolapse were seen. Laparotomy was done in four of 6,078 instances. Two patients died of septic complications. Whenever possible, we prefer vaginal hysterectomy because of its low complication rate, low mortality rate and low postoperative morbidity.

Elevated thrombin-antithrombin III complex concentrations in patients with gynaecological malignancy.

In patients with malignant tumors a high incidence of haemostatic disorders occurs. The reaction of thrombin with its major inhibitor antithrombin III (AT III) leads to the formation of a stable complex, which represents a sensitive marker for the activation of intravascular coagulation. In 153 patients suffering from different kinds of gynaecological malignancy thrombin-antithrombin III-complex (TAT) levels were measured. In 21 cases the course of the disease was studied. Of 153 patients with gynaecological malignancy 102 (67%) showed TAT plasma concentrations above the normal range before therapy. Seven patients with elevated TAT levels before treatment showed a decrease of TAT concentrations to the normal range when no evidence of disease was obvious. In 5 cases TAT levels were in the normal range before and after successful therapy, 4 patients with tumor progression and 5 patients with tumor recurrence showed an increase of TAT levels. The TAT plasma concentrations correlated with the presence or absence of the tumor. Measurement of TAT plasma concentrations in gynaecologic malignancies can detect any thromboembolic risk for the patient and in addition can reveal information about the course of the disease.

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear.

In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.

Complications of vaginal hysterectomy under "difficult" circumstances.

Vaginal hysterectomy is less invasive than hysterectomy performed via the abdominal approach. The vaginal approach may be made difficult by prior conisation, a need to remove the adnexae or marked uterine enlargement requiring morcellement. In this retrospective study we have investigated the impact of these factors on the incidence of complications in 1912 patients subject to vaginal hysterectomy. We have studied the incidence of intraoperative hemorrhage, bladder damage, hemorrhage up to 48 h after surgery, hemorrhage up to 14 days after surgery, vault abscesses or collections and pelvic peritonitis. In patients with prior morcellement, intraoperative hemorrhage was significantly more frequent. All other complications were not significantly increased by the intraoperative difficulties specified above. Thus even "difficult" vaginal hysterectomy would seem to carry low morbidity.

Thrombin-antithrombin III complex levels in normal pregnancy with hypertensive disorders and after delivery.

The plasma concentration of the thrombin-antithrombin III-complex (TAT) was investigated during uncomplicated pregnancy in 15 women in the first, 22 in the second and 46 in the third trimester, and in 19 women with hypertensive disorders between 25 and 40 weeks gestation. Eight women at term after a normal pregnancy were studied before the onset of labour and within 60 min and 24 h after delivery. A comparison group of 16 healthy, non-pregnant women was investigated. The mean TAT concentration in normal pregnancies increased significantly in the second and third trimester compared with values in the first trimester and in non-pregnant women. In the group with hypertensive disorders during pregnancy TAT levels were significantly higher than in uncomplicated pregnancies. Within 60 min after delivery a distinct increase of TAT concentrations occurred compared to levels before the onset of labour but the levels had returned to normal by 24 h after delivery. Our findings suggest that an activation of the coagulation system occurs in normal pregnancy. A further activation takes place immediately after delivery. The significantly increased TAT levels in pregnancies with hypertensive disorders suggest a state of chronic disseminated intravascular coagulation leading to an enhanced consumption of and a decreased plasma concentration of antithrombin III.

Relationship between plasma levels of components of the fibrinolytic system and acute-phase reactants in patients with uterine malignancies.

Plasma samples from 17 patients with endometrial cancer and from 52 patients with cervical carcinoma were determined with respect to their levels of components of the fibrinolytic system (tissue-type plasminogen activator antigen, urokinase-type plasminogen activator antigen, plasminogen activator inhibitor activity) and related to the observed alterations of three acute-phase reactants (C-reactive protein, coeruloplasmin, alpha-1-antitrypsin). As shown previously, uterine malignancies, especially at later stages, exhibited significant increases in plasma levels of urokinase-type plasminogen activator antigen as compared to an age-matched control group. In contrast, tissue-type plasminogen activator antigen and plasminogen activator inhibitor activity remained unchanged. Determination of the acute-phase reactants revealed significant changes in the case of C-reactive protein and coeruloplasmin in later tumour stages. However, the increase in urokinase-type plasminogen activator antigen did not correlate with the increase of either C-reactive protein or coeruloplasmin plasma level. These data indicate that the increase in plasma urokinase-type plasminogen activator antigen in patients with uterine malignancies does not follow the pattern of common acute-phase reactants, like C-reactive protein or coeruloplasmin.

Squamous cell carcinoma (SCC) antigen in patients with invasive cervical carcinoma during primary irradiation.

In a prospective study, serum concentrations of squamous cell carcinoma (SCC) antigen were determined by radioimmunoassay from 74 healthy volunteers and 54 patients with cervical carcinoma who underwent irradiation therapy. 5.4% of the controls had SCC levels greater than 3.0 ng/ml, which was considered as upper limit of the normal range. 31/54 (57.4%) patients and 60% of the patients with SCC had elevated pretreatment levels. In all patients with pretreatment serum levels above 3.0 ng/ml, SCC serum levels decreased during irradiation therapy. 4/5 patients with posttreatment levels greater than 0.5 ng/ml developed recurrence or persistence of tumor, 1 patient could not be followed up. Good conformity was found between SCC antigen serum levels and therapy response. SCC antigen determinations during and after therapy provide a useful tool in detecting progression and persistence of tumor.