[Diagnostic image (98). A woman with a vanished intra-uterine device]. / Diagnose in beeld (98). Een vrouw met een verdwenen spiraaltje. IUD in de vrije buikholte door uterusperforatie.

A 36-year-old woman suffered from abdominal pain immediately after placement of an intra-uterine device (IUD). Abdominal X-ray revealed that the IUD had perforated the uterus and lay in the peritoneal cavity.

[Ovarian vein thrombosis]. / Vena-ovaricatrombose.

A 44 year-old woman was admitted with fever and lower abdominal pain at the right side suggestive of appendicitis. Ovarian vein thrombosis was diagnosed by sonography and confirmed by contrast-enhanced CT scan. After heparinisation the complaints disappeared and fever resolved in less than 72 hours. Repeated radiological investigation showed regression of the thrombus. Ovarian vein thrombosis is an uncommon, potentially fatal disorder that can be adequately treated with medication. The cornerstone of the diagnosis consists in non-invasive radiological investigation.

CA 125 half-life in ovarian cancer: a multivariate survival analysis.

Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemotherapy was studied in 60 ovarian cancer patients and compared to known prognostic factors. Various methods reported in the literature to calculate a CA 125 half-live value were compared. Using two exponential regression models (Van der Burg et al., 1988; Buller et al., 1991), mean half-lives in stage I-II patients after complete cytoreductive surgery were respectively 10.7 days (range: 5-23) and 9.8 days (range: 7-15). Within stage III-IV patients, a significant positive correlation was seen between survival and (a) stage III (P = 0.002), (b) residual tumour < or = 1 cm (P = 0.02), (c) CA 125 normalisation after three courses (P = 0.003) and (d) CA 125 half-life < or = 20 days (P = 0.02-0.004, depending on the method used for half-life calculation). The median survival times of patients with and without a CA 125 normalisation after three courses were 27 and 14 months respectively (P = 0.003). When using the model of Buller et al. patients with a CA 125 half-life < or = 20 days had a median survival of 28 months compared to a median survival of 19 months for patients with CA 125 half-lives > 20 days (P = 0.004). Half-life calculations only showed a significant correlation with survival, if pre-surgery CA 125 levels were used as a baseline. In a survival analysis using the Cox proportional hazards model, stage of disease was the most predictive variable for survival (P = 0.006). The only additional independent prognostic factor for survival was the CA 125 half-life calculated according to Buller [derived from the formula: CA 125 = exp. [i-s x (days after surgery)], in which i is the y-axis intercept and s is the slope of the CA 125 regression curve]. A CA 125 half-life < or = 20 days vs > 20 days calculated using this formula, provides an independent prognostic factor for survival in stage III-IV patients early in the course of therapy (P = 0.04).

Evaluation of colorectal cancer-associated mucin CA M43 assay in serum.

The technical performance of a newly developed assay for CA M43, a serum marker for colorectal cancer, was evaluated and its preliminary clinical potential assessed. The heterologous double-determinant enzyme immunoassay for the detection of the tumor-associated mucin CA M43 utilizes two monoclonal antibodies (CT 43 and CT 66) selected for their binding capacity to two distinct epitopes present on mucins in the sera of patients with colorectal cancer. CT 66 recognizes both Lewis(a) and sialylated Lewis(a) antigen; CT 43 is directed toward a mucin epitope of an as-yet uncharacterized structure. Precision experiments revealed interassay CVs of 11.8%, 5.9%, and 4.9% at 9.3, 11.9, and 78.9 units/mL, respectively; intraassay precision was 2.0% at 95.1 units/mL. The upper normal value was set at 7.5 units/mL, which included 99% of the values found in healthy controls. In colorectal cancer patients, CA M43 showed a positivity rate equivalent to that of carcinoembryonic antigen (CEA) and superior to that of CA 19.9, with only one CA 19.9-positive serum being negative for CA M43. Interestingly, CA M43 appeared to be complementary to CEA, with CA M43 and CEA together reaching 87% positivity in metastatic disease.

CA 125 in gynecological pathology--a review.

The original CA 125 serum tumor marker test is a homologous double-determinant (OC 125 monoclonal antibody based) assay for the quantification of tumor associated mucin-like CA 125 molecules present in the serum. Commercial kits, now supplied by various manufacturers (and in different versions, e.g. IRMA, EIA, etc.) are currently widely applied in the following clinical situations: (i) Monitoring of disease. Doubling or halving of CA 125 serum values correlated (in 87% of all cases) with tumor progression or regression, respectively. (ii) Early prediction of outcome. Deviation from the ideal CA 125 regression curve predicts poor outcome within 3 months of cytostatic treatment. (iii) Tumor status after completion of therapy. Patients with CA 125 > 35 U/ml have (in 95% of all cases) still tumor present (at second look surgery). However, patients with CA 125 < 35 U/ml have in 50% (mostly minimal) residual disease. (iv) Early detection of recurrence. After a complete remission, a rise in CA 125 precedes tumor recurrence in 75% of all patients, with lead times up to more then 1 year, surpassing the CT-scan in cheapness and accuracy. (v) Diagnosis and differential diagnosis. Only when used in combination with other markers, do CA 125 determinations have a value as a diagnostic adjunct in the discrimination of ovarian cancer patients from those with benign ovarian tumors and from those with advanced colon cancer. Today, optimal management of ovarian cancer patients can only be provided using the CA 125 serum test.

CA 125 serum levels in the early post-operative period do not reflect tumour reduction obtained by cytoreductive surgery.

In order to assess whether CA 125 serum levels reflect the outcome of cytoreductive surgery, CA 125 antigen levels were determined prior to and after debulking surgery in 50 ovarian cancer patients and compared to CA 125 serum levels before and after surgery in a control group of 140 patients undergoing laparotomy for various malignant or benign diseases. A significant CA 125 decrease in the first post-operative week was seen in 56% of ovarian cancer patients whereas 26% remained stable and 18% showed a significant increase after surgery. Although removal of tumour had been complete in all 14 stage I-II ovarian carcinomas, only 2 of these patients showed a subsequent significant CA 125 decrease after cytoreductive surgery, while 4 patients showed a significant increase. Such increases of CA 125 following surgery were also seen in uterine carcinomas (30%), in gastrointestinal carcinomas (75%) and in patients after laparotomy for benign gynaecological diseases (23%). CA 125 pre-treatment levels were significantly lower in patients with post-operative increases than in patients with stable or decreasing CA 125 patterns. Patients with stable CA 125 levels also had lower CA 125 pretreatment levels compared to patients with a post-operative CA 125 decrease. Post-operative increases were observed for at least 2 weeks after debulking in the case of ovarian cancer. Pre-operative levels of these patients were either within the normal range or moderately elevated. Serial measurements during surgery in partial debulking showed a rapid CA 125 decline within 24 h followed by increasing CA 125 values thereafter. Our data indicate that CA 125 serum levels in the direct post-operative period do not always reflect the outcome of cytoreductive surgery. There appears to be an effect on CA 125 levels caused by the abdominal surgical procedure itself. Consequently, CA 125 levels after abdominal surgery should be interpreted with caution.

Hydatidiform mole with coexisting twin pregnancy after gamete intra-fallopian transfer.

The pregnancy of a 31-year-old infertility patient is described. After gamete intra-Fallopian transfer, her pregnancy evolved uneventfully until the 18th week of gestation, when vaginal bleeding occurred. Ultrasonographic findings suggested a molar pregnancy with two live fetuses. At 24 weeks gestation, two male infants were spontaneously delivered. Fetal (46 XY) and molar (46 XX) karyotypes and post-mortem findings were consistent with a bizygotic twin pregnancy associated with a complete hydatidiform mole. The pathogenesis and obstetrical management are discussed.

Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas.

In the search for a method to facilitate the preoperative discrimination of ovarian carcinomas from colorectal carcinomas serum levels of 6 tumor markers were measured in 47 patients presenting with ovarian cancer and compared to levels found in 24 female patients with advanced, untreated colorectal cancer. The markers studied were CA 125, CA 15.3, CA 19.9, CEA and two recently developed mucin markers, CA M29 and CA M26. Levels of CA 125, CA 15.3, CEA and CA M29 showed significant differences between both groups. In predicting ovarian cancer, sensitivity was highest for CA 125 at 94% (35 U/ml cutoff level). However, the specificity of CA 125 was at 71% low. Specificity increased significantly by using a combination of a CA 125-positive score (greater than 35 U/ml) and a simultaneous negative CEA score (less than or equal to 5 ng/ml) (specificity 100%, sensitivity 81%). A CA 125/CEA serum ratio greater than 25 resulted in the highest discriminative power with a specificity of 100% and a sensitivity of 91% resulting in an overall test accuracy of 94%. It is concluded that the serum tumor markers used, especially a combination of CA 125 and CEA, are helpful in the preoperative differential diagnosis between adenocarcinomas of ovarian and colorectal origin.

Monoclonal antibodies that discriminate between human ovarian carcinomas and benign ovarian tumours.

Three hybridoma cell lines producing monoclonal antibodies (MAbs) against ovarian carcinomas were obtained after immunizing mice with an undifferentiated human ovarian cystadenocarcinoma extract. The hybridoma cell supernatants were initially screened for a positive immunohistochemical reaction with ovarian carcinomas concomitant with a negative reactivity with a benign ovarian cystadenoma. The antibodies OV-TL 15 (IgM), OV-TL 30 (IgG1) and OV-TL 31 (IgM) reacted positively with 84, 84 and 74% of the ovarian carcinoma samples (n = 76) respectively. Reactivity with ovarian cysts and cystadenomas (n = 21), with non-ovarian carcinomas (n = 77) and with normal human tissue samples (n = 63) was absent or limited to weak reactivity on incidental samples. All three antibodies were shown by immunoelectron microscopy to react with surface antigens (OA 15, OA 30 and OA 31) of ovarian carcinoma cells. Cross reactivity between OV-TL 15, OV-TL 30, OV-TL 31 and OC 125 monoclonal antibodies was excluded by competitive binding assays on NIH:OVCAR-3 cells. Antigen levels (OA 15 and OA 31) in tumour extracts and cyst fluids were quantified by immunoradiometric assays and compared to the CA 125 antigen levels. High levels of CA 125, OA 15 and OA 31 were found in cyst fluids from ovarian cancers. In benign ovarian cyst fluids, however, the CA 125 content was also high while OA 15 antigen was hardly detectable. The OA 31 antigen was present at relatively low levels. The IRMA data confirmed the immunohistochemical data showing that, in contrast to OC 125, the newly developed MAbs OV-TL 15, OV-TL 30 and OV-TL 31 discriminate between benign ovarian cystadenomas and malignant ovarian cancers.

Clinical applications of monoclonal antibodies against ovarian cancer-associated antigens.

Monoclonal antibodies (McAbs), reactive with tumour-associated antigens (TAAs) present on tumour cells, appear to offer new possibilities in the diagnosis and treatment of cancer (Table I). In addition to these prospects for clinical application, monoclonal antibodies also serve as useful instruments in basic cancer research. The hybridoma technology initiated by Köhler and Milstein in 1975, underwent a very rapid development and has now shown its potential in the field of oncology. This technique made it possible to produce very large quantities of homogeneous antibodies of a stable quality. These McAbs often recognize only one antigenic determinant, or epitope, of cell surface and other molecules. This high specificity is essential for in vivo applications, especially in therapeutic immunotargeting. A central question is whether the antibodies can reach and identify those antigens on ovarian tumour cells that are not shared with normal tissues. Various antibodies have been described in the field of gynaecological oncology, which are assumed to be capable of recognizing such ovarian tumour-related antigens. These McAbs, single or in combination, are capable of showing, unambiguously, the presence of various tumour-associated antigens on ovarian carcinoma cells either in tissue or, when antigen shedding occurs, in blood. However, these McAbs may also react with tumour-associated antigens present on endometrial, cervical, colorectal, breast or other carcinoma cells. The original immunogens used to generate these McAbs differ as to their origin: ovarian cancer cells, breast cancer cells, human milk-fat preparations, trophoblastic cells, endometrial cancer cells have been used as well as osteogenic sarcoma cells, epidermoid carcinoma cells and small-cell lung cancer, colorectal, pancreatic and laryngeal carcinoma cells. The histological distribution patterns of the antigens recognized by these McAbs vary widely: cross-reactions with normal tissue and with carcinomas different from those used as immunogen are frequently seen.