A double-blind placebo-controlled study with granulocyte-macrophage colony-stimulating factor during chemotherapy for ovarian carcinoma.

In a placebo-controlled double-blind dose-finding trial, 15 patients with ovarian cancer stage III or IV received daily s.c. 1.5, 3, or 6 micrograms/kg recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). At each dose step three patients received recombinant human GM-CSF, and two received placebo. Chemotherapy comprised 6 cycles of carboplatin, 300 mg/m2, and cyclophosphamide, 750 mg/m2, by i.v. bolus on day 1 every 4 weeks. GM-CSF, given on days 6-12 on an outpatient basis, raised the mean leukocyte count on days 7, 10, and 15 and the mean neutrophil count on days 7 and 10 at all dose levels as compared with the control group. Neutrophil counts of less than 0.5 x 10(9)/liter occurred in 20 of 22 cycles in the control group and in 5 of 17 cycles at the 6-micrograms/kg/day GM-CSF dose level (P less than 0.0005). In comparison with the control group, the mean eosinophil count was higher on days 10 and 15 at all GM-CSF doses, as was the mean monocyte count on day 15. The mean platelet count was raised at the 3- and 6-micrograms GM-CSF doses on days 15 and 22. Chemotherapy dose reduction or postponement due to myelotoxicity occurred in 9 of 28 cycles in the placebo groups versus 5 of 44 cycles in the GM-CSF group (not significant). Local skin infiltrates at the GM-CSF injection sites occurred in 8/9 patients, leading to premature removal of two patients from the study. Capillary leakage of 131I-albumin was increased in all patients 5 days after the first chemotherapy course but was not significantly affected by 4 days of GM-CSF treatment. Tumor necrosis factor alpha and C-reactive protein serum levels increased during GM-CSF administration at the 6-micrograms dose level, but interleukin 6 serum levels were not affected. We conclude that a dose of 3 and 6 micrograms/kg/day GM-CSF reduces the severity of neutropenia and thrombocytopenia after carboplatin-cyclophosphamide. This GM-CSF dose does not induce additional capillary leakage.

Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas.

PURPOSE: To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS: Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS: P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION: Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.

Recombinant human interleukin-3 to dose-intensify carboplatin and cyclophosphamide chemotherapy in epithelial ovarian cancer: a phase I trial.

PURPOSE: To define the optimal dose of recombinant human interleukin-3 (rhIL-3) required to intensify the dose of carboplatin and cyclophosphamide for advanced epithelial ovarian cancer. PATIENTS AND METHODS: Seventeen patients were treated on day 1 with carboplatin (dose adjusted for creatinine clearance: range, 257 to 385 mg/m2; median, 300 mg/m2) and cyclophosphamide (750 mg/m2). rhIL-3 5 micrograms/kg/d (n = 10) or 10 micrograms/kg/d (n = 7) was administered subcutaneously (SC) on days 2 through 11. Carboplatin dose was escalated if no postponement of cycles 1 to 3 had occurred. RESULTS: A 3-week interval was achieved in 62% of cycles and a 4-week interval in 81%, with no difference between the rhIL-3 doses. A neutrophil nadir less than 0.5 x 10(9)/L occurred in 35% of the cycles at 5 micrograms/kg/d and in 52% at 10 micrograms/kg/d of rhIL-3 (nonsignificant difference). The mean platelet nadir in cycle 1 was 173 +/- 78 x 10(9)/L at 5 micrograms/kg/d and 340 +/- 152 x 10(9)/L at 10 micrograms/kg/d of rhIL-3 (P < .05), with a faster recovery of platelets at 10 micrograms/kg/d (P < .05). Progressive myelotoxicity occurred for leukocytes and platelets at both rhIL-3 doses and required chemotherapy postponement in later cycles. The planned six cycles were completed by 41% of patients. Fever (> or = 38.5 degrees C) occurred in 38% of cycles at 5 micrograms/kg/d and in 97% at 10 micrograms/kg/d (P < .0005); headache and myalgias occurred in 30% and 44%, respectively. After two cycles, diffuse erythema, facial edema, and urticaria were observed in two patients at 5 micrograms/kg/d and in five patients at 10 micrograms/kg/d of rhIL-3. This resolved after discontinuation of rhIL-3 and administration of corticosteroids and antihistamines. CONCLUSION: A dose of 5 micrograms/kg/d of rhIL-3 proved to be optimal to intensify the carboplatin and cyclophosphamide regimen. It permitted the administration of carboplatin and cyclophosphamide combination therapy every 3 weeks in 62% of cycles.

Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma.

PURPOSE: To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. PATIENTS AND METHODS: Sera from 653 women treated for squamous cervical cancer between 1978 and 1994 were analyzed for the presence of SCC-ag and related to clinicopathologic characteristics and patient outcome using univariate and multivariate analyses. RESULTS: Increased pretreatment SCC-ag levels correlated strongly with unfavorable clinicopathologic characteristics (International Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P < or = .00005]; stages IB and IIA: tumor size [P = .0236], deep stromal infiltration [P = .00009], and lymph node metastasis [P = .0001]). After multivariate analysis, elevated pretreatment serum SCC-ag levels (P = .001), lesion size (P = .043), and vascular invasion by tumor cells (P = .001) were independent predictors for the presence of lymph node metastases. In Cox regression analysis, controlling for SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and lymph node status only the initial SCC-ag level had a significant independent effect on survival (P = .0152). Even in node-negative patients, the risk of recurrence was three times higher if the SCC-ag level was elevated before therapy. CONCLUSION: The determination of pretreatment serum SCC-ag level provides a new prognostic factor in early-stage disease, particularly in patients with small tumor size. In future trials to assess the value of new treatment strategies, pretreatment serum SCC-ag levels can be used to help identify patients with a poor prognosis.

Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva.

PURPOSE: To determine the diagnostic accuracy of the sentinel lymph node procedure in patients with squamous cell carcinoma of the vulva and to investigate whether step sectioning and immunohistochemistry of sentinel lymph nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS: Between July 1996 and July 1999, 59 patients with primary vulvar cancer were entered onto a two-center prospective study. All patients underwent sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with technetium-99m-labeled nanocolloid and intraoperative blue dye). Radical excision of the primary tumor with uni- or bilateral inguinofemoral lymphadenectomy was performed subsequently. Sentinel lymph nodes and lymphadenectomy specimens were sent for histopathologic examination separately. Sentinel lymph nodes, negative at the time of routine pathologic examination, were re-examined with step sectioning and immunohistochemistry. RESULTS: In 59 patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and 48 bilateral). All sentinel lymph nodes, as observed on preoperative lymphoscintigram, were identified successfully intraoperatively. Routine histopathologic examination showed lymph node metastases in 27 groins, all of which were detected by the sentinel lymph node procedure. The negative predictive value for a negative sentinel lymph node was 100% (97.5% confidence interval [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that were negative at the time of routine histopathologic examination. CONCLUSION: Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.

Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer.

PURPOSE: To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. PATIENTS AND METHODS: Follow-up data were evaluated in patients with early-stage squamous cell cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy. Routine serum SCC-ag determination was performed at each follow-up visit. RESULTS: Recurrent disease occurred in 35 (16%) of 225 patients and was preceded or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical indicator. Desite salvage therapy, all five patients died of disease. In the other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or positive signs led to recurrence detection. Median survival time after recurrence was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag value at recurrence in comparison with patients with normal serum SCC-ag values (20 months; range, 4 to 96; P <.01). In 23 of the 190 patients without recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23 patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven patients benign (especially skin) disorders were found. CONCLUSION: Serum SCC-ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival. As long as treatment possibilities for recurrent cervical cancer patients are not improved, serum SCC-ag analysis should not be carried out in routine follow-up.

Aspects of surgery in ovarian and endometrial carcinoma.

In ovarian cancer and endometrial cancer the surgeon plays an important role in both the staging procedure and in the removal of as much of the tumour as possible. Although uniform treatment policies have not been developed, a better understanding of the pattern of spread in both tumours allows for accurate staging and can be of help in selecting patients for more extended treatment and saving others from unnecessary overtreatment.

CA-125 in ovarian cancer: relation between half-life, doubling time and survival.

In a retrospective study of 35 patients with stage III-IV ovarian cancer, the probability to reach a complete (CR) or partial remission (PR) was studied by comparing the initial level, half-life and normalisation time of CA-125 during chemotherapy. In 15 CR patients, pretreatment CA-125 level was lower (70 U/l, range 16-1500 U/l) than in 20 PR patients (800 U/l, range 60-9000 U/l). The median normalisation time (NT) was 6 weeks in CR (range 0.7-5.5 months) and 4 months in PR patients (range 1.2-9 months). Marker half-life was 12 days for the CR group (range 4.5-30 days) and 21 days for the PR group (range 5.5-39 days). Remission duration (r = 0.56) and log cell kill (r = 0.72) were correlated with survival. Combining initial tumour diameter, marker level and NT predicted CR in 87.5% and PR in 86%. Estimating log cell kill by combining marker half-life and doubling time gives more insight into tumour cell kinetics and individual survival.

Phase II study of high-dose megestrol acetate in patients with advanced ovarian carcinoma.

The EORTC Gynaecological Cancer Cooperative Group conducted a phase II study of high dose oral megestrol acetate: 800 mg/day for 1 month followed by 400 mg/day as maintenance treatment, in heavily pretreated patients with ovarian cancer. Of 72 patients included in this study, 54 were fully evaluable for response and toxicity. The response rate was low with only 1 patient having a partial response, 9 patients with stable disease and 44 patients with progressive disease. The toxicity profile was low. However, 1 patient died after 2 months of treatment, and in 3 patients thrombo-embolic events occurred. Weight gain varied in 20 of the 61 patients from 0.5 to 16 kg. This study does not suggest that the overall 10% benefit from hormonal therapy for chemotherapy refractory ovarian cancer will improve by increasing the dose.

Risks and benefits of cisplatin in ovarian cancer. A quality-adjusted survival analysis.

Both the efficacy and toxicity of short intensive cisplatin-based chemotherapy was established in an unselected group of patients with stage III-IV ovarian cancer. The impact of this treatment on quality of life (QOL) was assessed by the TWIST index, expressed as Time Without Symptoms of Treatment and Disease, in relation to the individual length of progression free survival (PFS). Sixty-eight patients were treated with six cycles of a combination of cyclophosphamide, Adriamycin and cisplatin (CAP-5), every 4 weeks. Patients with a clinical response to treatment were evaluated by second look laparotomy (SLL), which could be performed in 52 patients. There were 20 pathological CR, seven microscopic disease, 17 PR and eight SD in these 52 patients. Median follow up at evaluation was 22 months. The median progression free survival (PFS) was 18 months and the median overall survival 22 months. The median duration of TWIST was 10 months, indicating that about 8 months were lost to symptoms due to treatment or hospital admissions for chemotherapy or laparotomy. Of 45 patients receiving six cycles, only eight patients had no symptoms of peripheral neuropathy, and four patients were free of nephropathy at the end of treatment. The overall survival for this limited duration of treatment is similar to that after more protracted treatment. Despite its limited duration, however, about 28% of the cumulative period of progression free survival is consumed by the treatment and its side-effects. Correction of PFS by TWIST may be a suitable instrument to compare the impact of different cytotoxic schedules on quality of life.

Intraperitoneal human recombinant interferon alpha-2b in minimal residual ovarian cancer.

Twenty evaluable patients with minimal residual ovarian cancer at second look laparotomy were treated with human recombinant interferon alpha-2b (IFN) intraperitoneally. The dose administered was 50 x 10(6) units once weekly for 8 weeks. Seventeen patients were evaluated by a relaparotomy: five had a pathological complete remission, four a partial response, six patients disease stabilization and two patients had progression. Three patients, two stable and one with clinical progression, had no laparotomy. Nine of the 11 patients with residual tumor smaller than 5 mm had a response, while no response was found in six patients with residuals over 5 mm. The median duration of CR is 11+ months (6-13+ months) after evaluation. For toxicity, 156 treatment cycles could be studied. Fever was seen in 80% of all cycles within 24 h following administration of IFN, in 58 cycles (37%) over 38 degrees C and in 65 cycles (43%) over 39 degrees C. Abdominal pain was slight in 32% and moderate in 3% of all cycles. The peripheral blood leukocyte counts dropped after 52% of all cycles, in 27% below 4.0, in 22% below 3.0, and in one patient below 2.0 x 10(9)/l. IFN dosage was not reduced for leukopenia, but in one patient reduction was necessary for thrombopenia, resulting from insufficient marrow reserve after a previous autologous bone marrow transfusion. Pharmacokinetic studies showed i.p. IFN levels 50-100 times the blood levels. Blood levels were still elevated 2 days after i.p. infusion, but normalized within 1 week on repeated administration. At the second instillation, lower peak serum levels were reached. In conclusion, high doses of i.p. IFN appear to be active in patients with minimal residual disease, with ongoing response in CR patients. Apart from general malaise on the day of treatment, toxicity was acceptable. IFN may be active in patients with minimal residual ovarian cancer through local as well as systemic effects.

Prognostic factors and changing trends in the treatment of Stage I endometrial cancer: a clinical and histopathological study of 182 patients.

Changing trends in treatment of Stage I endometrial carcinoma are reflected in the modalities used in the University Hospital in Groningen. From 1969 to 1979, three treatment regimes have been used in 182 patients with Stage I disease: Group A (50 patients): preoperative uterine radium packing followed by surgery six weeks later; Group B (94 patients): preoperative low dose external irradiation (14 Gray) immediately followed by surgery and an additional 40 Gray in patients who had invasion of the myometrium beyond the inner one-third; Group C (38 patients): primary surgery with post-operative radiation therapy. No significant differences were found in the 5-year actuarial survivals of 92, 90 and 88% in Groups A, B and C respectively. Most recurrences were seen in Group B (16%) as compared to 10% in Group A and 8% in Group C. Poor prognostic factors were found to be myometrial infiltration beyond the inner one-third, dedifferentiation of the tumor (Grade 2 and 3), vascular invasion, age over 60 years, and uterine length over 8 cm. The advantages of primary surgery, allowing for accurate surgical-pathological examination and individualization of postoperative irradiation, are stressed.

Sentinel lymph node identification with technetium-99m-labeled nanocolloid in squamous cell cancer of the vulva.

UNLABELLED: In patients with early-stage squamous cell cancer of the vulva, inguinofemoral lymphadenectomy is performed primarily as a diagnostic procedure. The morbidity of this procedure, however, is not negligible. The aim of this study was to evaluate the feasibility of minimally invasive detection of the sentinel inguinofemoral lymph node (SILN) and to investigate whether the histopathology of the SILNs is representative of that of the other non-SILNs. METHODS: Patients with early-stage squamous cell cancer of the vulva, planned for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, were eligible for the study. Technetium-99m-labeled nanocolloid was injected intradermally at four locations around the tumor the day before operation. Images were recorded immediately and after 2.5 hr using a gamma camera. SILN locations were marked on the overlying groin skin. The next day, during general anesthesia, blue patent dye was injected intradermally at the same locations around the tumor. During the operation SILNs were identified at the place indicated using a handheld gamma-detection probe. It was noted if SILNs were found by the probe, by blue dye or by both techniques. After resection of the SILNs, a standard inguinofemoral lymphadenectomy was performed. The results of histopathology of the SILNs were compared with those of the non-SILNs. RESULTS: The procedure was well tolerated by 10 of 11 patients. One patient, initially agreeing to participate, refused the injection of tracer because of fear of pain. In all 10 patients, identification of the SILNs was successful. The mean time for identification was 11 min. Identification of SILNs was primarily performed using the hand probe in all patients, whereas in 10 of 18 removed SILNs afferent lymph channels were also blue stained (56%). In 8 patients, pathologic examination showed no metastatic disease in both SILNs and non-SILNs, whereas in 2 patients metastases in the SILNs (one and two metastatic lymph nodes, respectively), as well as in other non-SILNs, were found. CONCLUSION: This study shows that identification of SILNs in squamous cell cancer of the vulva is feasible with preoperatively administered 99mTc-labeled nanocolloid. Intraoperatively administered blue dye was only useful for confirmation of identification with nanocolloid. To date, no false-negative SILNs have been found, but expansion of the study is necessary to determine the possible clinical application of this new diagnostic technique.

Hemolytic uremic syndrome in a patient on cis-platinum, vinblastine and bleomycin.

A 23-year-old woman with metastatic Sertoli-Leydig cell tumor was treated with cisplatin, vinblastine, and bleomycin. Hemolytic uremic syndrome appeared, while no evidence of residual tumor was found. Infusion of fresh frozen plasma together with aspirin and dipyridamole resulted in recovery of microangiopathic hemolytic anemia and thrombocytopenia. Renal insufficiency, however, persisted.

Chemotherapy-resistant gestational trophoblastic neoplasia treated successfully with cisplatin, etoposide, and bleomycin.

This report describes a 53-year-old white woman with metastatic gestational trophoblastic neoplasia that recurred after evacuation of an accidental pregnancy and did not respond sufficiently to treatment with a combination of methotrexate, actinomycin D, and chlorambucil. After second-line treatment with a combination of cisplatin, etoposide, and bleomycin, there was a complete remission. Afterward, the patient suffered from a moderate bleomycin pneumonitis, which resolved spontaneously. She is now free of disease and feeling well 60 months after her last treatment.

Analysis of cryolesions in the uterine cervix: application techniques, extension, and failures.

Although cryosurgery is regularly used for treatment of cervical intraepithelial neoplasia (CIN), there are few data concerning freeze technique and attendant extension of the cryolesion. This study evaluated how to create cryolesions extensive enough to eradicate the CIN lesion completely. The way the extension of the cryolesion was influenced by type of probe, anatomical position in the cervix, shape of the external os, and freeze time was analyzed. Furthermore, we examined whether localization of the cryolesions corresponded with the CIN III location. Cryosurgery was applied to the cervix of 64 women the day before hysterectomy was performed for benign disease. Four types of probes were tested and freezing was done with a double freeze cycle. After extirpation of the uterus, slides were cut at the 3-, 6-, 9-, and 12-o'clock positions. With a computerized graphic tablet, the depth and linear extension of the cryolesion were measured morphometrically. After short freeze times, it appeared that an adequate lesion was present in only 67.4% of the slides. The large cone probe gave the best results; the small flat cervix probe the worst. At the 3- and 9-o'clock positions, a significantly higher percentage of inadequate lesions was found (60.8 and 65.3%, respectively). This proved to be due primarily to the extensive vascular supply at those positions. Longer freeze times gave an excellent result within all slides, even at the 3- and 9-o'clock positions. The topographic position of the cryolesion corresponded completely in all cases with that of the CIN III lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Minimum extension and appropriate topographic position of tissue destruction for treatment of cervical intraepithelial neoplasia.

Minimum extension and topographic position of tissue destruction for treatment of cervical intraepithelial neoplasia (CIN) is determined by the extension and the localization of the pathologic epithelium. In 65 cone specimens, we studied the depth of CIN II crypt involvement and the linear extent and topographic position of the CIN III lesions. The topographic position of the CIN III lesion was related to a reference point R, the most caudal point of the ectocervix. The mean maximum depth of CIN III crypt involvement appeared to be 1.6 +/- 1.0 mm, and the mean linear extent of the CIN III lesion was 7.4 +/- 3.7 mm. The distal border of the CIN III lesion was located at a mean distance of 8.2 +/- 4.4 mm from the reference point R, and the proximal border at a mean distance of 13.3 +/- 3.7 mm. Taking the mean + 2 SD values as directives (97.7% of the population) suggests that in almost all patients, the depth of crypt involvement did not exceed 3.6 mm; the linear extent of the CIN III did not exceed 14.8 mm. Furthermore, this implies that in almost all patients, the CIN III lesion was located between 0.6 mm distally (mean - 2 SD) and 20.7 mm proximally (mean + 2 SD) from the reference point R. Based on these results, we conclude that minimum local tissue destruction for treatment of CIN should have a depth of 4 mm over a distance of 15 mm, and should be localized at least between 1 mm distally and 21 mm proximally from the most caudal point of the ectocervix.

Tumor markers CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix.

Between 1978-1987, 439 patients with primary cervical carcinoma were admitted to our department. Seventy-seven patients (17.5%) had cervical adenocarcinoma and are reviewed in this retrospective study. Serial serum samples of these 77 patients were analyzed for cancer antigen 125 (CA 125), squamous cell carcinoma antigen, and carcinoembryonic antigen. Before treatment, only elevated serum CA 125 levels varied directly with the clinical stage of disease. In stages IB and II disease (International Federation of Gynecology and Obstetrics [FIGO]), the incidence of elevated serum CA 125 levels was highest in patients with adenosquamous tumor. Serum marker levels, measured 3 months after therapy, concurred with the treatment results. At that time, 17 of the 23 cases (74%) with at least one elevated serum marker level either had residual disease (N = 9) or developed recurrent disease during follow-up (N = 8), compared with six of the 40 cases (15%) with normal serum marker levels (P less than .001). Increasing serum marker levels during follow-up coincided with or preceded the clinical detection of recurrent disease. Tumor relapse, clinically located in the vaginal vault, occurred concomitant with a rise of at least one serum marker level in six of the seven cases (86%). All 15 patients with abdominal recurrence showed elevation of CA 125. In progressive disease, very high serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels were determined in patients with adenosquamous tumor, whereas patients with adenocarcinoma demonstrated only high CA 125 levels. We conclude that all three markers are important for monitoring patients with cervical adenocarcinoma.

Detection, prevalence, and prognosis of asymptomatic carcinoma of the cervix.

Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis. Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease. Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA. In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years. To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department. Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening. In the age category 35-55 years, 54 of 160 (34%) were asymptomatic. Patients aged 35-55 years had undergone population screening or incidental screening. In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients. Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence. Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence. Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status.

Karyotyping and DNA flow cytometry of metastatic ovarian yolk sac tumor.

We karyotyped a metastasis composed of pure yolk sac tumor derived from a primary ovarian germ cell tumor with two components: a dermoid cyst [DNA index (DI) 1.0] and a pure yolk sac tumor (DI 1.88). The metastatic yolk sac tumor had a hypertriploid karyotype and a DI of 1.78 and lacked the germ cell tumor marker i(12p). The absence of this marker in a metastasis from a tumor with a dermoid cyst component might be indicative for a pathogenesis of the yolk sac tumor similar to that of a dermoid cyst and different from that of dysgerminoma.