Biomedical subjects

P Kenemans

Publications and source records attributed to P Kenemans.

At least 163 records · Page 9Linked to original sources

PubMed1993

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.

Adult↗

PubMed1993

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).

Adult↗

PubMed1993

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions.

Cervical intraepithelial neoplasia (CIN) grades I to III lesions (n = 94) and squamous cell carcinomas of the uterine cervix (n = 27) were analysed for MHC class I and II expression and presence of HPV genotypes. MHC class I and II expression was studied by immunohistochemistry and HPV typing was performed by general primer- and type-specific primer mediated PCR (GP/TS PCR). Both techniques were performed on paraffin embedded tissue sections. Results show disturbed MHC class I heavy chain expression in CIN I to CIN III, as well as in cervical carcinomas. Upregulated MHC class II expression on dysplastic epithelial cells was also found in the different CIN groups and carcinomas. Prevalence of HPV genotypes increased with the severity of the lesion, mainly due to the contribution of the HPV types 16 and 18. No correlation could be established between the presence of specific HPV genotypes and any MHC expression pattern in the different CIN groups or cervical carcinomas. In some cases these data were confirmed by RNA in situ hybridisation showing HPV 16 E7 transcripts in the same dysplastic/neoplastic cells from which MHC status was determined. The results indicate that local differences may exist in the type of cellular immune response to HPV induced lesions.

Carcinoma, Squamous Cell↗

PubMed1993

Characterization of cytotoxic T lymphocyte epitopes of a self-protein, p53, and a non-self-protein, influenza matrix: relationship between major histocompatibility complex peptide binding affinity and immune responsiveness to peptides.

We previously described a motif prediction of major histocompatibility complex allele-specific peptides and an in vitro assay for actual measurement of peptide binding to human leukocyte antigen HLA-A2.1 molecules. Using this method we have identified candidate cytotoxic T lymphocyte (CTL) epitopes derived from a non-self-protein (influenza matrix) and self-protein (p53). We now show that results of binding assays performed over a range of peptide concentrations indicate that distinct differences in HLA-A2.1 peptide binding affinities exist between the influenza matrix and p53 protein. The results for the influenza matrix protein indicate that the peptide that shows the highest binding affinity to HLA-A2.1 is identical to the known immunodominant peptide recognized by influenza virus-specific CTLs. The results for p53 indicate that one of the peptides with a low binding affinity is capable of inducing specific CTL responses, but CTLs recognizing the highest affinity binding peptides were not obtained. These findings are discussed in terms of the distinct implications for induction of cellular immune responses directed against peptides with different binding affinities for HLA-A2.1 of proteins that constitute attractive targets for tumor immunotherapy.

Amino Acid Sequence↗

PubMed1993

Heterologous double-determinant immunoradiometric assay CA 125 II: reliable second-generation immunoassay for determining CA 125 in serum.

The new CA 125 II (Centocor) serum assay utilizing the M11 mouse monoclonal antibody as capture antibody and OC125 as tracer antibody, was investigated for its technical and clinical performance against the original CA 125 assay. The CA 125 II test revealed a quadruple increase in signal-to-noise ratio, good intra- and interassay precision (with CVs < 5% and 7%, respectively), improved dilution linearity, and a minimal detectable dose of 0.38 units/mL. Sera were obtained from healthy females (n = 192), women with benign conditions (n = 208), and patients with various cancers (n = 379). Both assays measured highly similar CA 125 distributions with equal reference ranges and nearly identical positivity (> 35 units/mL) rates, resulting in similar receiver-operating characteristic curves and monitoring graphs. Linear regression analysis of results by the two assays (CA 125 = x, CA 125 II = y) in ovarian cancer patients showed, for CA 125 assay values between 0 and 1000 units/mL, a slope of 1.00 and a y-intercept of 12.6 (n = 254, r = 0.8617, P < 0.0001). The heterologous CA 125 II assay appeared to be more accurate in patients who had human anti-mouse antibodies after immunoscintigraphy. The CA 125 II immunoradiometric assay is sensitive and reliable for measuring serum CA 125, and fully retains the cutoff values of 35 and 65 units/mL that were defined with the original CA 125 immunoradiometric assay.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1993

MHC class I expression in HPV 16 positive cervical carcinomas is post-transcriptionally controlled and independent from c-myc overexpression.

Squamous cell carcinomas of the uterine cervix (n = 23) were selected for the presence of human papillomavirus type 16 (HPV 16) using the polymerase chain reaction (PCR). Localization of transcripts coding for the E7 protein was demonstrated in neoplastic cells with RNA in situ hybridization. Consecutive tissue sections were investigated for expression of the major histocompatibility complex class I (MHC-I) and c-myc using immunohistochemical double staining procedures, since a role has been suggested for the c-myc protein in MHC-I down-regulation and c-myc overexpression has been described in cervical carcinomas. Reduced expression of class I heavy chains was observed in neoplastic cells from 18 out of 23 carcinomas (78%). Varying levels of c-myc overexpression were observed in 12 carcinomas (52%), from which four showed positive MHC-I expression in c-myc overexpressing cells. In the remaining eight c-myc overexpressing carcinomas MHC-I down-regulation was observed. Additional RNA in situ hybridization with class I heavy chain locus-specific RNA-probes revealed presence of class I mRNAs in those neoplastic cells that show negative staining for MHC-I protein. These data strongly indicate that MHC-I down-regulation in cervical carcinomas involves post-transcriptional mechanisms, not directly related to E7 transcription and overexpression of c-myc.

Carcinoma, Squamous Cell↗

PubMed1993

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.

Adult↗

PubMed1992

Comparison of five immunoassay procedures for the ovarian carcinoma-associated antigenic determinant CA 125 in serum.

Interassay variability in CA 125 values was studied in 77 serum samples (covering a range of CA 125 values between 8.9 and 310 arb. U/ml as measured by the original Centocor RIA) using three 125I-labeled RIA kits (Centocor, Byk and Cis) and two enzyme-labeled immunoassays (Abbott and Roche). Taking the Centocor RIA as a reference, orthogonal regression equations resulted in slopes varying between 0.74 and 1.35, with y-axis intercepts varying between -6.5 and +6.2, and correlation coefficients ranging from 0.88 to 0.94. Compared with the results of the Centocor RIA, the EIAs of Abbott and Roche gave overall lower CA 125 values, whereas the Cis and the Byk RIAs gave higher assay results. At the 35 arb. U/ml Centocor cut-off, serum levels with the other assays varied between 23 and 53 arb. U/ml. The 65 arb. U/ml cut-off level corresponded with CA 125 serum levels between 45 and 94 arb. U/ml. When classifying CA 125 values in three clinically relevant categories based on Centocor RIA results, ('normal' < or = 35 arb. U/ml, 'slightly elevated' > 35- < or = 65 arb. U/ml and 'elevated' > 65 arb. U/ml), discordances ranged from 26% with the Cis RIA to 40% utilizing the Byk RIA. The five CA 125 assays tested do not give equal assay results. As a consequence, the interpretation of CA 125 serum concentrations should be done with caution in disease monitoring and in the assessment of ovarian masses, especially when using different serum assays.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1992

Multiple HPV 16-related squamous cell carcinomas of the vulva, vagina, anus, skin and cervix in a 31-year-old woman.

A 31-year-old woman is reported with in the genital region multiple squamous carcinomas of the skin (buttock), vulva, vagina, anus and cervix uteri. All these carcinomas were HPV 16 positive as tested by DNA in situ hybridization. The existence of areas with normal epithelium between all tumor localisations and the absence of distant metastases indicate multicentric development of these multiple carcinomas. The presence of HPV 16 DNA in all carcinoma cells, as detected by DNA in situ hybridisation, argues for an etiological role of HPV 16 in the development of these multiple tumors.

Adult↗

PubMed1992

Borderline malignancy of the ovary and controlled hyperstimulation, a report of 2 cases.

We report 2 patients who developed a borderline malignancy of the ovary after treatment with follicular stimulants in the context of an in vitro fertilisation (IVF) programme. In both cases, conservative surgery for the borderline malignancy was sufficient treatment. Ultimately, both patients became pregnant, 1 after IVF treatment and 1 without treatment, and both delivered healthy babies. In addition to the presentation of both cases, the literature concerning the possible risks of treating patients with high dosage, exogenously administered hormones is reviewed and the possible association between exogenous hormones and the risk of developing ovarian cancer is discussed.

Adult↗

PubMed1992

Diathermy loop excision in the management of cervical intraepithelial neoplasia: diagnosis and treatment in one procedure.

OBJECTIVE: Diathermy loop excision was performed as a new diagnostic-treatment in patients with cervical cytologic diagnoses consistent with an epithelial abnormality. STUDY DESIGN: A total of 424 patients with cervical cytologic diagnoses consistent with an epithelial abnormality, but macroscopically or colposcopically not consistent with invasive carcinoma, were subjected to diathermy loop excision to diagnose and treat cervical lesions in one procedure. RESULTS: The diagnostic accuracy rate was 99%. In patients with histologically confirmed grade 3 cervical intraepithelial neoplasia, pretreatment cytologic diagnosis and subsequent histopathologic diagnosis corresponded in 73% of cases. In 91% of all patients the diathermy loop excision was sufficient for complete treatment. Cervical morphologic findings after treatment allowed adequate cytologic follow-up. There was no evidence that diathermy loop excision influenced fertility or pregnancy outcome. CONCLUSION: Diathermy loop excision is a reliable, well-tolerated, inexpensive, and efficient technique for the management of cervical intraepithelial neoplasia. This outpatient procedure is especially recommended in younger patients, because diathermy loop excision preserves the function of the cervix.

Electrocoagulation↗

PubMed1992

Urinary and faecal incontinence in community-residing elderly women.

The prevalence of urinary and faecal incontinence was investigated in a sample of 1049 women aged 60 years and over in the municipality of Amstelveen, the Netherlands; 719 postal histories were completed. The overall prevalence of urinary incontinence was 23.5%. Daily urine loss was reported by 14.0% of all women. In women aged 60 to 84 years and 85 years and over 4.2% and 16.9% were faecally incontinent, respectively. In all age groups poor mobility and frequency were associated with urinary incontinence. Urgency was independently associated in women aged 60-85 years as was nocturia in women aged 85 years and over.

Age Factors↗

PubMed1992

Successful treatment with methotrexate of five vital interstitial pregnancies.

Five patients with vital, unruptured interstitial pregnancies of less than 3 cm maximum diameter were treated successfully with methotrexate and leucovorin rescue. Four pregnancies showed cardiac activity. Diagnosis was established with transvaginal ultrasonography in all patients. The human chorionic gonadotrophin serum levels were measured to monitor the effectiveness of therapy. This is the first publication on methotrexate treatment for interstitial twin pregnancy and the first on instillation of methotrexate after puncture and aspiration of interstitial pregnancy. In all cases, total and uneventful regression of trophoblast tissue was achieved. No adverse reactions were observed. The advantages and drawbacks of these therapeutic approaches are discussed. Methotrexate appears to be an effective medical non-surgical treatment for unruptured interstitial pregnancy with or without cardiac activity, and preserves reproductive potential.

Adult↗

PubMed1992

Tumour detection and localization using 99Tcm-labelled OV-TL 3 Fab' in patients suspected of ovarian cancer.

Fab' fragments of the monoclonal antibody OV-TL 3, that recognizes an ovarian carcinoma-associated antigen (OA3), were labelled with 99Tcm using D-glucarate as a ligand. Twenty patients suspected of having primary or recurrent ovarian cancer received intravenously 1 mg of the Fab' labelled with 740 MBq 99Tcm. Both planar and single photon emission computed tomographic (SPECT) scintigraphy were performed up to 30 h after intravenous infusion. In 19 out of 20 patients surgical and histopathological evaluation was performed between 2 and 6 days postinfusion. Imaging results were compared with X-ray computed tomography (CT), ultrasonography (US) and CA 125 serum level. Blood clearance was fast with median t1/2 beta of 9.5 h. Thirty-seven per cent of the injected dose (% ID) was excreted in the urine within the first 24 h, whereas 7% ID was excreted in the 24 h faeces. In one patient with an OA3 negative ovarian carcinoma, radioimmunoscintigraphy (RIS) did not visualize the tumour. In two other patients a benign ovarian cyst was found, also showing no elevated uptake. In 13 out of 17 patients ovarian cancer lesions were detected with RIS, whereas CT and US detected lesions in, respectively, 15 and 12 patients. Of 36 surgically defined tumour deposits larger than 1 cm in diameter, 53% were detected and localized with RIS, whereas CT and US detected 61 and 40%, respectively. Radioimmunoscintigraphy with 99Tcm-OV-TL 3 Fab' is less distressing for the patients but the overall imaging performance is not improved when compared with 111In-OV-TL 3 F(ab')2.

Adult↗

PubMed1992

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.

Adenocarcinoma↗

PubMed1992

The utility of lipid-associated sialic acid (LASA or LSA) as a serum marker for malignancy. A review of the literature.

The utility of the lipid-associated sialic acid (LASA or LSA) test as a serum marker for malignancy is reviewed. The name LASA or LSA test is confusing because it suggests that only or mainly lipid-bound sialic acid is measured. In reality, glycoprotein-bound sialic acid is determined predominantly. The assay appears to have a particularly high positivity rate in leukemia, Hodgkin's disease, melanoma, sarcoma, advanced ovarian carcinoma and oropharyngeal tumors, suggesting that LASA may serve as a valuable marker in these malignancies. As a consequence of the rise of sialic acid-rich acute-phase proteins, such as alpha 1-acid glycoprotein, in inflammatory diseases the specificity of LASA and therefore its diagnostic accuracy is low. LASA can be useful for monitoring cancer patients during treatment, especially in combination with other tumor markers.

Antigens, Neoplasm↗

PubMed1992

Detection of human papillomavirus in cervical scrapes by the polymerase chain reaction in relation to cytology: possible implications for cervical cancer screening.

An HPV screening strategy based on general primer-mediated and type-specific PCR is described. A relationship was found between an increasing HPV prevalence rate and a higher degree of cervical dysplasia (up to 100% in cervical carcinoma). Based on these prevalence studies in the Netherlands and preliminary data showing that progression of cervical lesions is always associated with persistent infection of oncogenic/high-risk HPV types, a cervical cancer screening scheme incorporating PCR-based HPV detection is proposed for use in industrialized countries.

Cervix Uteri↗

PubMed1992

Specific and nonspecific immunoassays to detect HAMA after administration of indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody to patients with ovarian cancer.

The development of human anti-mouse antibodies (HAMA) may cause problems in radioimmunotargeting studies, but may also improve survival of patients. To identify the presence of HAMA in blood samples from patients intravenously injected with 1 mg of 111In-labeled OV-TL3-F(ab')2, we developed three specific OV-TL 3-based HAMA assays and tested these along with two commercially available nonspecific HAMA assays (Sorin and Immunomedics). The specific assays were positive for HAMA with 10 postinjection serum samples from 7 patients. Eight of the 10 samples were also HAMA positive with one or both nonspecific HAMA assays. Conflicting results were observed with half the number of samples. The two nonspecific assays also reacted positively with another 11 serum samples from 5 patients including their preinjection samples. Despite some contradictory results, the nonspecific HAMA assays identify both pre-existent and Mab-induced HAMA, whereas the specific OV-TL3-based HAMA assays identify specific immune-responses occurring after the OV-TL 3 injection.

Animals↗