Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma.

PURPOSE: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. PATIENTS AND METHODS: In a randomized multicenter study, 185 patients received carboplatin (dose based on projected area under the concentration-time curve [AUC]=4) and cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously on days 3 to 12. RESULTS: Adherence to chemotherapeutic regimen, mean chemotherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-primarily allergic reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which resulted in 21 discontinuations compared with one in the placebo group. Compared with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6. The number of patients with World Health Organization (WHO) grade IV thrombocytopenia or number of platelet transfusions did not differ. Leukocyte counts differed only in cycles 1 and 2 between groups. The leukocyte nadir occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15, P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001). CONCLUSION: rhIL-3 had stimulatory hematopoietic effects. This did not result either in reduction of platelet transfusions or in improvement of chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen.

A 15-year overview of management and prognosis in primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.

The relevance of adjuvant therapy in primary carcinoma of the fallopian tube, stages I and II: irradiation vs. chemotherapy.

INTRODUCTION: Primary carcinoma of the Fallopian tube (FTC) is a rare but extremely aggressive neoplasm. It must be expected to cause up to 40% of tumor-related deaths even in Stage I, and up to 57% in Stage II. Due to its rarity, there exist only a few and divergent reports on the value of adjuvant therapy. Therefore the present study aims at evaluating the influence of postoperative adjuvant therapy on FTC by studying the effects of irradiation and chemotherapy on the overall survival of patients in Stages I and II. PATIENTS AND METHODS: We investigated 95 cases of FTC in Stages I (n = 66) and II (n = 29) in a retrospective multicenter study. Group I (n = 32) are patients who underwent a complete irradiation with cobalt or photon energies of 23 MV (administering a daily dose of 2 Gy resulted in a total of 45-52 Gy in the pelvic areas). Group II (n = 31) consists of those cases who received postoperative chemotherapy with platinum. Thirty-two women were excluded from this study because they had other chemotherapies, incomplete irradiation, or no adjuvant therapy at all. RESULTS: Median survival time was 57 months in Group I patients (95% confidence interval 33-81 months), compared to 73 months (95% confidence interval, 68-78 months) in the chemotherapeutically treated Group II. This difference did not prove to be statistically significant (p = 0.476).If primary surgical therapy is included in the evaluation, and patients with total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) are compared to those with additional radical lymphadenectomy (TAH+BSO+lymph nodes), the latter group's overall survival essentially improves but fails to reach statistical significance. Their 5-year survival rate is 83% against 58% in the TAH+BSO group (p = 0.12). CONCLUSION: Chemotherapy and irradiation are two adjuvant therapies that are similarly effective in FTC of Stages I and II, with chemotherapy being preferred at the present time. Primary surgical treatment, however, is of crucial impact on the prognosis of FTC.

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.

PURPOSE: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. METHODS AND MATERIALS: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). RESULTS: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011). CONCLUSION: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

Lymphadenectomy in primary carcinoma of the Fallopian tube.

OBJECTIVE: The bad prognosis of primary carcinoma of the Fallopian tube is ascribed to early lymphogenous metastasis. Due to the rarity of cases, there exist only few and divergent results on the importance of lymph node metastasis in the relevant literature. Thus, our study aimed at detecting the incidence of lymph node metastases and their influence on overall survival, as well as at evaluating the therapeutic effect of radical lymphadenectomy. METHODS: We studied 158 cases of primary carcinoma of the Fallopian tube in a retrospective multicenter analysis. Group I (n = 38) consisted of patients who were subjected to radical pelvic and para-aortic lymphadenectomy in addition to total abdominal hysterectomy, bilateral adenectomy and omentectomy. The control group II (n = 71) underwent the same surgical procedures but without radical lymphadenectomy. Patients who received post-operative irradiation (n = 49) were excluded from the study. RESULTS: On average, 38 lymph nodes (range 12-68) were extirpated. In group I 42.1% of the cases showed lymph node metastases. Lymphatic dissemination was observed only after the carcinoma had spread beyond the organ (intraabdominal stage II); the incidence of lymph node metastases rose significantly (P = 0.02) with growing intraperitoneal tumour masses. Pelvic and para-aortic metastases occur simultaneously. Overall survival with tumour of equal size is markedly, but not significantly reduced (P = 0.18) if the lymph nodes are involved. If, however, radical lymphadenectomy is performed (group I) the median survival time increases to 43 months (95% confidence-interval 20-66), compared with 21 months (95% confidence-interval 10-32) in group II (P = 0.095). CONCLUSION: Correct staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy. Radical lymphadenectomy in tumours of equal size may markedly prolong survival.

Tumor progression, histologic grading and DNA-ploidy as predictive factors of lymphogenous metastasis in primary carcinoma of the Fallopian tube.

UNLABELLED: The bad prognosis of primary carcinoma of the Fallopian tube (FTC), with 5-year overall survival rates of only 35%, is particularly ascribed to lymphogenous metastasis. Yet, we know very little on the pathophysiologic factors on which this lymphogenous metastasis is based. The present study, therefore, aims at evaluating the influence of intra-abdominal tumor progression and tumor-cell anaplasia on lymphogenous metastasis in FTC. We studied 41 cases of FTC, who had been subjected to radical lymphadenectomy during primary operation in a retrospective analysis. Staging was done by International Federation of Gynecology and Obstetrics-classification. Histologic grading and nuclear DNA-content (DNA-index) were used for evaluating tumor-cell anaplasia. Histologic grading discriminated between highly differentiated (G1), moderately dedifferentiated (G2), and dedifferentiated (G3) tumors. According to their DNA-indices, tumors were separated into three groups: DNA-index < or =1.1 (euploid cases), DNA-indices between 1.1 and 2.0 (cases of intermediate ploidy), and DNA-index >2.0 (aneuploid cases). The overall incidence of lymph node metastases was 43.9%. There was no correlation between histologic grading and DNA-index (P=0.98). Lymphogenous metastasis set in after the tumor had transgressed the tube (intra-abdominal stage II). Further intra-abdominal tumor progression (including omentum, liver, or peritoneum) significantly increases the incidence of lymph node metastases (P=0.02). There was only a single G1-tumor that had already disseminated into the lymph, all other cases of lymph node metastases were found in G2- or G3-tumors. DNA-index and the extent of lymphogenous metastases were not found to be correlated (P=0.74). CONCLUSIONS: The extent of lymphogenous metastases in FTC depends above all on intra-abdominal tumor progression. This fact has clinical consequences as the indication for lymphadenectomy can be obtained directly during operation. The results of histologic grading are of no impact on the surgical proceedings; the determination of DNA-ploidy is negligible.

Prognostic impact of DNA content and AUER classification in primary fallopian tube carcinoma.

DNA ploidy has been studied in 61 primary fallopian tube carcinomas using image-cytometry. The investigation also included survival analysis, and ploidy classification according to AUER was performed in order to evaluate its prognostic impact for fallopian tube carcinoma. A high number of aneuploid cases were observed (79% aneuploid vs. 21% euploid tumors). The high incidence of aneuploid tumors was consistently observed among all FIGO-stages as well as all groups of histologic grading. There was no correlation between ploidy and FIGO-stage or histologic grading. Patients with euploid DNA content showed a median survival of 34 months compared to 24 months for aneuploid cases (log-rank, P = 0.83). No correlation between the AUER classification and FIGO-stage or histologic grading could be observed. Tumors with an AUER type I and II (75th quantile 41 months) showed a better outcome than tumors with AUER III and IV (75th quantile 19 months). Although these results did not reach statistical significance (P = 0.07), a trend could be observed. Therefore AUER classification may be useful as an objective prognostic parameter. The high incidence of aneuploid tumors could be an expression of the high biologic aggressiveness of primary fallopian tube cancer which has been repeatedly mentioned in the past.

Cervical intraepithelial neoplasia III: long-term outcome after cold-knife conization with clear margins.

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia or squamous cell carcinoma in situ (CIN III) after cold-knife conization with clear margins. METHODS: A total of 4417 women (mean age 36, range 18-72 years) with histologically confirmed CIN III had cold-knife conization with clear margins at our institution between 1970 and 1994. All patients were followed up with colposcopy, cytology, and pelvic examination for a mean of 18 years (range 5-30years). RESULTS: New high-grade squamous intraepithelial lesions (SILs) (CIN II and III) developed in 15 (0.35%) patients (mean age 35, range 25-65 years) after a median of 107 (range 40-201) months. A total of 4402 (99.65%) patients (mean age 36, range 18-72 years) were free of high-grade SILs after a mean follow-up of 18 (range 5-30) years. High-grade glandular intraepithelial lesions developed in two (0.05%) patients 14 and 17 years after conization. Twelve (0.3%) patients had metachronous vulvar intraepithelial neoplasia (VIN) grade III or vaginal intraepithelial neoplasia (VAIN) grade III, and one (0.02%) patient had invasive vaginal carcinoma 10 years after conization. CONCLUSION: Cold-knife conization with clear margins was an adequate method to definitively treat CIN III.

Influence of inflammatory reaction in primary fallopian-tube carcinoma (stage-I and stage-ii).

A retrospective evaluation of 68 Fallopian tube carcinomas (FTC) of a period of ten years (1980-1990) in stage I and II was performed. The aim of this study was to evaluate the prognostic impact of various factors. 68 cases were investigated for the prognostic influence of mitotic activity, degree of nuclear anaplasia and inflammatory reaction. Histological grading (p=0.08), and inflammatory reaction (p=0.003) showed to have a prognostic impact for survival in univariate analysis. Whereas, mitotic activity did not show any statistically significant influence. 47 (69%) tissue samples showed a positive inflammatory reaction which correlated with a significantly better outcome compared with tumors without this feature. However, this influence was proved in multivariate analysis for inflammatory reaction only (p=0.01). Although no data on the influence of the inflammatory reaction on prognosis in FTC has been published up to now, we can state that the determination of this factor can be useful for prognosis in this rare but highly aggressive tumor.

Adaptative intima fibrosis in blood vessels in cervical carcinomas after preoperative cytotoxic chemotherapy.

Angiogenesis is an important component of tumor growth. After preoperative cytotoxic chemotherapy, tumor blood vessels of a large caliber become increasingly tortuous and their lumens narrow. The narrowing of the vessel lumens results from fibrosis of the intimal layer, which is called adaptative intimal fibrosis (AIF). We describe AIF in three patients with cervical cancer after a complete or partial response to preoperative cytotoxic chemotherapy. Two patients with no residual disease in the surgical specimen had severe AIF and are free of disease at 12 and 124 months. The patient with residual disease had only moderate AIF and developed a recurrence. AIF has not been described in cervical cancer. Our findings suggest that AIF may be a morphologic correlate of tumor regression following preoperative cytotoxic chemotherapy.

Abdominopelvic computed tomography in the preoperative evaluation of suspected ovarian masses.

To evaluate the efficacy of computed tomography (CT) in 175 patients scheduled to undergo surgery for a suspected ovarian mass, we compared preoperative CT findings with the findings at surgery and histology. At surgery, 115 patients were found to have epithelial ovarian malignancies (20 stage 1, 7 stage II, 50 stage III and 38 stage IV) while 60 had benign pelvic tumors. CT findings were suggestive of malignancy in 4 (7%) of 60 patients with benign tumors and suggestive of benign disease in 3 (3%) of 115 patients with malignant ovarian tumors; 30% of all scans were inconclusive. The sensitivity of CT for predicting pelvic or para-aortic lymph node involvement in 42 patients who underwent lymphadenectomy was 62 and 70%, respectively; the specificity was 100%. The results of this series suggest that the routine use of CT in the preoperative evaluation of patients does not seem justified.

Consolidation radiotherapy following carboplatin-based chemotherapy in radically operated advanced ovarian cancer. A pilot study.

Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. Five (23%) of the patients were discontinued on this protocol because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of 10 Stage III ovarian cancer patients who received chemoradiotherapy and were evaluable for assessment of treatment efficacy was retrospectively compared with the survival of 11 Stage III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no clinical evidence of disease.

Prognostic factors in cervical cancer.

The inadequacy of clinical methods has spurred efforts to develop objective, measurable and reproducible parameters for the spread and growth behaviour of cervical cancer. Morphological methods were applied first. They can be used only on the surgical specimen, but are accessible to biometry. The presented results are based on 479 surgical specimens obtained at radical abdominal hysterectomy for cervical cancers of different sizes. The specimens were processed as frontal giant sections with the cervix, the vaginal cuff and the parametria on both sides. The median follow-up time was 7-8 years. Statistical correlations were found between follow-up data, biometric morphologic criteria and survival. The statistical ranking of the significant prognostic factors produced the following order: lymph node metastases, size of lymph node metastases, tumour volume, parametrial involvement and vascular invasion.

Remission induction with carboplatin-epirubicin-prednimustine followed by consolidation radiotherapy in advanced ovarian cancer.

Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no clinical evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. This protocol was discontinued for five (23%) patients because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of ten stage-III ovarian cancer patients, who received chemoradiotherapy and were evaluable for assessment of treatment efficacy, was retrospectively compared with the survival of 11 stage-III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no evidence of disease.

Primary serous papillary carcinoma of the peritoneum: a report of 18 patients.

Eighteen patients with primary papillary serous carcinoma of the peritoneum (PPSCP) were treated at the Department of Obstetrics and Gynecology of the University of Graz between 1980 and 1996. Primary tumours from other sites, particularly the pancreas and ovary, had been excluded. Because of extensive spread of the disease particularly in the upper abdomen, seven of the 18 patients (38%) underwent exploratory laparotomy only. Median overall survival time was 10 months (range 1-28+). This figure reflects the extent of spread of the disease at diagnosis on one hand, and that optimal cytoreductive surgery (residual disease < or = 2 cm) was possible only in six of the 18 patients (33%) on the other. The six patients with optimal cytoreduction had a better survival (range 4+ to 28+ months) than those who underwent less radical surgery. These data indicate, that, similar to primary ovarian cancer, the amount of residual disease may be an important prognostic factor in patients with PPSCP.

Prognostic significance of preoperative DNA flow cytometry in surgically-treated cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of preoperative DNA flow cytometry compared with other clinical and histologic variables in cervical carcinoma. STUDY DESIGN: Sixty-four patients with FIGO Stage Ib-II cervical cancer treated with radical abdominal hysterectomy and systematic pelvic lymphadenectomy were analyzed. The mean follow-up was 3.4 (range 0.3-9.8) years. DNA flow cytometry was performed with fresh tumor tissue. Four biopsies were recut from the surgical specimen within 30 minutes of the operation. The ectocervix was divided into four quadrants and a specimen obtained from each. DNA-low-grade tumors (diploid, near-diploid, tetraploid and near-tetraploid) were distinguished from DNA-high-grade tumors (aneuploid and hypoploid). Carcinomas with more than one non-diploid stem line were considered heterogeneous. An S phase fraction >7% was classified as low, 7% - < 14% as moderate, and > or = 14 as high. DNA ploidy, DNA heterogeneity, S phase fraction and various clinical and histological variables were related to disease-free survival. RESULTS: In the univariate analysis patients with DNA-low-grade carcinomas had significantly better disease-free survival than patients with DNA-high-grade tumors (82% vs 45%, p = 0.021). Carcinomas with an S-phase fraction < 7% were associated with better disease-free survival (0.8) than those with an S-phase fraction 7% - > 14% (0.62) and those with > or = 14% (0.64), but this was not statistically significant. Cox stepwise regression analysis showed DNA-heterogeneity, age, grade, parametrial involvement and extrapelvic metastasis to be independent prognostic factors. CONCLUSION: DNA ploidy and DNA heterogeneity are of prognostic importance in cervical cancer. DNA flow cytometry may be used preoperatively to identify low-risk and high-risk patients within a given stage.

Solitary metastasis in the tarsus preceding the diagnosis of primary endometrial cancer. A case report.

A solitary metastasis in the left tarsus led to the diagnosis of primary endometrial cancer in a 61 year-old patient with no history of postmenopausal bleeding. Lower leg amputation, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy were performed. Histopathology showed a well-differentiated endometrioid adenocarcinoma of the uterus with a low mitotic rate, but infiltration of the outer third of the myometrium and lymph vessel invasion (FIGO Stage IVb). Immunostaining was positive for progesterone receptors, but negative for estrogen receptors and p53. The lymph nodes were free of metastases. Ascites was positive for malignant cells. Postoperatively the patient received carboplatin, cyclophosphamide and medroxyprogesterone acetate and is alive with no evidence of disease 10 months after diagnosis.

[Predictive value of a tumor marker combination for the monitoring of ovarian cancer]. / Der prädiktive Wert einer Tumormarkerkombination für das Monitoring beim Ovarialkarzinom.

The tumour markers carcinoembryonic antigen (CEA), ferritin, cancer antigen 125 (CA 125) and tissue polypeptide antigen (TPA) were measured by radioimmunoassay in sera from 80 patients with ovarian cancer pre-operatively, postoperatively, during cytostatic chemotherapy and on follow up. Discriminant analysis was applied to obtain retrospective classification of 60 patients into a group showing a favourable course of the disease (no recurrence, tumour regression) and into a group with an unfavourable course (recurrence, progression of the tumour). The classification was based on the introduction of the Cutting Score. By means of this bio-mathematical model it was possible to make at least a short-term prognostic statement in a further 20 patients. It is suggested that invasive diagnostic procedures may not be required in patients who are found to have normal tumour marker levels.

[Labile disulfide bonds and free thiol groups in human IgG. III. The "sigma S value" in gynecologic neoplasms]. / Labile Disulfidbindungen und freie Thiolgruppen im Human-IgG. III. Der "Sigma S-Wert" bei gynäkologischen Malignomen.

The immunoglobulins G contain labile disulfide bonds which can easily be opened by dithionitrobenzoic acid in the subclass G1, and free SH groups in the subclass G2. The "sigma S value" is a photometrically determined quantitative measure of both groups added together. 57 cases of different gynaecological malignant tumours gave a mean sigma S value of 1.02 +/- 0.24 and 7 cases of stage 0 a sigma S of 1.05 +/- 0.25, whereas in 45 cases of benign diseases the sigma S was found to be 1.45 +/- 0,21. The difference between the values in the malignant and benign cases was highly significant (p less than 0.001). The sigma S in the benign cases lies within the normal range ascertained with healthy serum donors. These results are in accordance with results formerly obtained with malignant tumours in other locations. This leads us to the assumption that the shift in sigma S may be functionally and/or symptomatically associated with malignancy. The decrease in sigma S is interpreted in terms of a decrease in the percentage of subclass G1 in the total IgG.

Labile disulfide bonds and free thiol groups in human IgG. IV. Use of the "sigma S" value for postoperative monitoring of gynaecological malignant tumors.

"sigma S" comprises both disulfide bonds reactive to dithionitrobenzoate, as well as free SH groups of serum immunoglobulin G. In 38 cases of invasive gynaecological tumors, the value of sigma S was ascertained to be 1.04 +/- 0.25 (mean +/- SD), which, in accordance with former results, differs significantly from the reference value of 1.51 +/- 0.36 (2 p less than 0.001). 14 days after surgery, at the latest, sigma S significantly increased to an average value of 1.33 +/- 0.26 (2p less than 0.001). This increase was apparently influenced by both the localisation, as well as by the completeness of removal of the tumors. Of 15 squamous cell carcinomas of the cervix uteri, 14 were radically removed and showed a highly significant postoperative increase in the sigma S value (2p less than 0.001). All of the 12 adenocarcinomas of the corpus uteri were totally removed and the sigma S increased significantly (2p = 0.05). Of 11 cystocarcinomas of the ovary, only 3 cases were completely operable. The remaining 8 cases had residual tumors with diameters greater than 5 cm. The postoperative increase in sigma S in these cases was not of statistical significance.