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Biomedical subjects

U Hørding

Publications and source records attributed to U Hørding.

At least 19 recordsLinked to original sources
PubMed1997

Prognosis of vulvar dysplasia and carcinoma in situ with special reference to histology and types of human papillomavirus (HPV).

Sixty-one women with vulvar dysplasia or carcinoma in situ were treated with local laser excision of the initial lesion and of the recurrences, and followed at intervals of from 3 increasing to 12 months. Recurrences were observed in 16 (26%) patients. No case of invasive carcinoma was seen. Patients with recurrences were significantly younger than those without (P < 0.02, median age 42.5 and 54 years, respectively). The resection borders were significantly more often involved in the initial lesions in the group with recurrences (36%) than in the group without (9%) (P < 0.014). All lesions were classified according to the WHO (mild, moderate, severe dysplasia or carcinoma in situ) and Toki et al. (1991) (warty, basaloid, combined warty/basaloid or mixed (warty, basaloid and simple). No pure types of Toki (1991) could be demonstrated. There were no differences regarding recurrences in any of these groups. HPV DNA was detected in the initial lesions by PCR in 50/56 (89%) (44 with HPV type 16 and 6 with HPV type 33) and by ISH in 23/61 (38%). The same type of HPV could be demonstrated in all first recurrences except in two, where HPV types 33 was shown in specimens harboring HPV type 16 in the initial lesions. In one of these cases, HPV type 16 could again be demonstrated in the second and final recurrence. In no specimen was more than one type of HPV detected. The results indicate that the most important parameter in predicting the recurrence of vulvar dysplasia or carcinoma in situ is the involvement of the resection borders. The location of the lesion, the degree and type of dysplasia, and the type of HPV seem to play a minor role. Local excision and subsequent intensive control with removal of any visible new lesion probably prevents development of vulvar invasive carcinoma.

Adult↗
PubMed1996

Use of tetranectin, CA-125 and CASA to predict residual tumor and survival at second- and third-look operations for ovarian cancer.

Tetranectin (TN), CA-125 and CASA were measured in serum prior to 63 second-look and 5 third-look operations for ovarian cancer. Patients with residual tumor had significantly lower levels of TN and higher levels of CASA and CA-125 compared with tumor-free patients. The predictive values PVPos = 100% and PVNeg = 50.9% were found for TN at 9.3 mg/l. For CASA, a predictive value PVPos = 100% was found at 10 U/ml with a corresponding PVNeg = 52.7%. At the cut-off 35 U/ml for CA-125, the PVPos was 100% and the PVNeg = 53.6%. By combining the markers, PVNeg increased to 61.7% with a PVPos on 100%. Significantly differences in survival were found by lifetable analysis between patients tested as positive and negative respectively for any of the markers. Using multivariate Cox analyses, it was found that every marker had an independent prognostic function for survival.

Adult↗
PubMed1995

Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential.

Seventy-three patients with vulvar intraepithelial neoplasia (VIN) grade III were followed for a median of 5 years after primary treatment. Thirty women also had a diagnosis of cervical neoplasia. During the follow-up 26 patients (36%) had one or more vulvar recurrences. Recurrences were seen significantly more often in the patients who also had cervical neoplasia, indicating a common etiology. Microinvasive carcinoma developed in 12 patients, 3 of whom later developed frankly invasive vulvar cancer. The original, paraffin-embedded vulvar specimens were examined by the polymerase chain reaction for human papillomavirus DNA of the types HPV 6, 11, 16, 18, and 33. HPV types 16 and 33 were found in 90% of the VIN lesions. It is concluded that VIN III is an HPV-related disease in all or almost all cases, and that a generalized genital HPV infection may be a factor in the development of multicentric genital neoplasia. No association was observed between the specific HPV type and the risk of recurrent vulvar disease, cervical neoplasia, or malignant progression.

Adult↗
PubMed1995

Ovarian carcinoma serum markers and ovarian steroid activity--is there a link in ovarian cancer? A correlation of inhibin, tetranectin and CA-125 to ovarian activity and the gonadotropin levels.

In a previous study, we have demonstrated that inhibin-production may be associated with improved survival and, also, that tetranectin (TN) is a valuable prognostic marker in ovarian epithelial cancer. We investigated the possible correlation between inhibin, tetranectin, CA-125, ovarian steroid activity and the gonadotropin levels. Preoperative serum levels of the tumor markers inhibin, tetranectin (TN) and CA-125 were measured and related to ovarian steroid function and the pituitary-gonadal axis (gonadotropin levels) in 28 postmenopausal ovarian cancer patients. The following median levels and 95% confidence limits were demonstrated for the tumor markers: Inhibin 0.4 U/l (0.2-0.9), TN 8.9 mg/l (6.8-9.2), CA-125 160 kU/l (75-687). A significant inverse correlation was demonstrated between inhibin and the gonadotropins. The Spearman correlation coefficients showed a highly significant correlation of inhibin with the examined ovarian steroid hormones except DHEAS which also has a suprarenal component. This indicates a synthesis of inhibin and the steroid hormones from the same cell compartment as known from the normal ovary and an apparently intact negative feed back mechanism. Inhibin may be produced in the normal ovary as a defense mechanism against an elevated gonadotropin level and inhibin acts by lowering the gonadotropins or by altering their biological activity. Elevated values of the tumor markers TN and CA-125 due to gonadotropin stimulation could not be demonstrated but a significant inverse correlation between TN and CA-125 was confirmed.

Adenocarcinoma↗
PubMed1994

Vulvar squamous cell carcinoma and papillomaviruses: indications for two different etiologies.

The vulvectomy specimens of 78 patients with vulvar squamous cell carcinoma were reviewed and examined for human papillomavirus (HPV) types 6, 11, 16, 18, and 33 by the polymerase chain reaction technique. The tumors were classified as keratinizing squamous cell carcinoma (KSC), as warty carcinoma (WC), and as basaloid carcinoma (BC). DNA of HPV types 16 and 33 was found in 2/51 KSC, in 12/17 WC, and in 10/10 BC. HPV types 6, 11, and 18 were not detected. Patients with WC and BC were younger, and 78% had VIN III lesions adjacent to the carcinoma. Patients with KSC were older and had a high incidence of dystrophic lesions, including lichen sclerosus, adjacent to the tumor. None of the KSC showed adjacent VIN III. In conclusion, vulvar carcinoma segregates into two categories, of which KSC seems to be the classic type, only rarely associated with HPV infection, and mostly affecting older women; WC and BC constitute an HPV-related subgroup of tumors occurring in younger patients and are associated with VIN III lesions from which they may emerge.

Adult↗
PubMed1994

Serum tetranectin and CA-125 used to monitor the course of treatment in ovarian cancer patients.

Serum tetranectin (Se-TN) and CA-125 were measured in serum samples obtained before primary surgery, before start of chemotherapy and monthly during chemotherapy in 8 patients with ovarian cancer. The median Se-TN level before chemotherapy (7.3 mg/l) increased significantly after the start of chemotherapy (13.7 mg/l), with the highest increase for one survivor (145%). Five patients who died of cancer in the study period, had pronounced decreases (30-50%) in Se-TN with a maximal concentration during chemotherapy to the lowest concentration in the last sample. One patient who died 10 months after closure of the study had continuously normal Se-TN values, but the last CA-125 value elevated. The lead time could be calculated in four patients for Se-TN and six patients for CA-125. Median lead times of 3.6 months and 3.8 months were found for Se-TN and CA-125 respectively. In conclusion, chemotherapy induces significant increases in Se-TN levels. A decrease in Se-TN during chemotherapy is highly suspect for recurrence and a poor outcome. Measurements of TN should therefore be included in other comparative studies.

Aged↗
PubMed1994

Detection of human papillomavirus (HPV) DNA in cervical swabs by the polymerase chain reaction: an evaluation of the sensitivity of the method in patients with HPV 16-harboring cervical lesions.

The polymerase chain reaction (PCR) was used to detect human papillomavirus (HPV) type 16 DNA in cervical swabs from 37 patients with HPV 16-harboring cervical lesions (15 carcinomas and 22 cervical intraepithelial neoplasias). Primers amplifying a sequence of the human beta-globin genome were used for internal control together with the HPV 16-specific primers. The cell samples were prepared for PCR analysis by two different methods: either by phenol/chloroform extraction or by boiling in the presence of a chelating agent. HPV 16 DNA was found in 27 swabs. The detection rates were identical with both methods of preparation. Four of the 10 false-negative swabs contained too little DNA to permit amplification with the genomic primers. Excluding these insufficient samples, the detection rate was 82%. Reasons for false-negative results may include low cell numbers or failure to obtain cells representative of the underlying lesion. In conclusion, the PCR offers a satisfactory method of HPV detection in cervical swabs. Cell preparation can be restricted to simple boiling with a chelating agent. For optimal results, samples containing less than 2 x 10(4) cells should be discarded, and genomic primers should be used for internal control.

Carcinoma↗
PubMed1994

Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours.

Epidemiological features suggest that the risk of testicular cancer may be related to exposure to unknown infectious agents, including viruses. Therefore a series of twenty specimens of testicular germ cell tumours, including preinvasive carcinoma in-situ, were tested for the presence of DNA sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace of EBV DNA was revealed in one of two experiments. These samples were examined by immunohistochemical staining with specific antibodies raised against the EBV protein products and in-situ hybridization with specific molecular probes, and were confirmed to be negative. The study indicates that a significant direct involvement of HPV and EBV in human testicular germ cell carcinogenesis is unlikely. However, a putative growth-stimulating role of EBV-transformed lymphocytes, which are frequently present in the stromal tissues of testicular tumours, cannot be excluded.

Cell Transformation, Viral↗
PubMed1994

Epstein-Barr virus and Hodgkin's disease: a comparative immunological, in situ hybridization, and polymerase chain reaction study.

During recent years numerous studies have demonstrated the presence of Epstein-Barr virus (EBV) in tissues affected by Hodgkin's disease (HD). The percentage of cases with evidence of EBV infection has varied among the different studies, a positive result being highly dependent on the sensitivity of the method employed. In this study three different methods of detecting EBV in 48 cases of 'classical' HD (33 cases of nodular sclerosis and 15 cases of mixed cellularity) were compared: Immunohistochemistry (IH) for detection of latent membrane protein-1 (LMP-1), in situ hybridization (ISH) for detection of Epstein-Barr virus early RNAs (EBER 1 and 2), and polymerase chain reaction (PCR) for detection of a reiterated 110 base-pair EBV genomic sequence of the BamHI region. In 14 cases (29%) Hodgkin's (H) and Reed-Sternberg (RS) cells were positive for LMP-1 using IH, and in 21 cases (44%) positive signals were seen in H-RS cells with EBER 1 and 2 probes using ISH. A few EBER-positive non-malignant lymphocytes were seen in 17 cases. Thirty-two cases (71%) were EBV-positive by PCR. It is concluded that the PCR technique is the most sensitive method for detecting EBV in HD. However, this method cannot provide information about the cellular localization of EBV. ISH with EBER 1 and 2 probes is superior to immunohistochemical detection of LMP-1 with regard to sensitivity. The advantage that the latter two methods have over the PCR techniques is that it is possible to analyse whether the EBV infection occurs in the H-RS cells or in the admixed non-malignant cell population. Furthermore, this study supports the observation that EBV is associated with a considerable number of HD cases.

Genome, Viral↗
PubMed1994

Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction.

Most nasopharyngeal carcinomas (NPCs) are of the nonkeratinizing or undifferentiated types, which are consistently associated with Epstein-Barr virus (EBV). The smaller group of highly differentiated, keratinizing NPCs seems to be only infrequently associated with EBV. In order to examine whether these rare tumors were related to another oncogenic virus, the authors used the polymerase chain reaction to examine paraffin-embedded sections of 15 keratinizing NPCs for human papillomavirus (HPV) types 6, 11, 16, and 18 genomic sequences. HPV DNA was found in 4 tumors (1 HPV-11-positive, and 3 HPV-16-positive tumors). None of 23 undifferentiated or nonkeratinizing NPCs harbored HPV DNA. The putatively oncogenic HPV type 16 may thus be involved in the carcinogenesis of some EBV-negative keratinizing squamous cell nasopharyngeal carcinomas.

Carcinoma, Squamous Cell↗
PubMed1994

The value of CA 125 measurement before second-look laparotomy in patients with ovarian carcinoma.

Serum CA 125 levels were evaluated in 71 patients undergoing second-look laparotomy for primary epithelial ovarian cancer. With a cut-off limit of 35 U/ml, 17 of 45 patients with residual disease (38%) were CA 125-positive. All of 26 patients with pathological complete response were marker-negative. Second-look laparotomy may be avoided in a select group of patients with elevated CA 125 values.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Epstein-Barr virus in exfoliated cells from the postnasal space. Viral detection by polymerase chain reaction is not a useful means of screening for nasopharyngeal carcinoma in high-risk populations.

There is a high incidence of undifferentiated nasopharyngeal carcinoma (NCP) in certain populations, including Greenland Eskimos. The cancer appears to have a causal association with Epstein-Barr virus (EBV), which is regularly found in NPC epithelial cells. With the aim of developing a method of screening or facilitating early diagnosis of NPC, we used the polymerase chain reaction to examine exfoliated nasopharyngeal cells for EBV in 54 Greenland and 17 white Danish subjects, none of whom was suspected of having NPC. EBV DNA was found in 81% of Greenland and 35% of Danish subjects. These findings support the concept of EBV infection leading in most cases to a chronic carrier state. It is concluded that EBV detection in nasopharyngeal cells is not at present a suitable method for identification of individuals at increased risk of developing NPC.

Base Sequence↗
PubMed1993

Immunoreactive inhibin-production in post-menopausal women with malignant epithelial ovarian tumors.

In post-menopausal women with a malignant epithelial ovarian tumor the follicle stimulating hormone (FSH) level was found to be significantly lower compared with healthy controls. We demonstrated immunoreactive (i.r.) inhibin in 20% of controls which was elevated to 60% of women with an ovarian tumor and correlating strongly to FSH in the tumor group (P = 0.0002). Steroid hormone levels were comparable in the two groups. In women with ovarian tumors the survival time for the i.r. inhibin-producing women was found to be 4.6 years compared with 0.9 year, or 5.1 times longer than in the non-producing women (P = 0.002). The site of i.r. inhibin production in these post-menopausal women is unknown, but i.r. inhibin production by the developing ovarian tumor or by the post-menopausal ovary may be regarded as a defense mechanism against an elevated gonadotrophin level (the gonadotrophin theory) which would promote further tumor growth. The recent suggestion that the alpha subunit of inhibin is a tumor suppressor gene is consistent with these results. The serum i.r. inhibin or alpha subunit concentrations might be used as an aid to diagnosis or as a prognostic indicator of survival in women with an ovarian carcinoma.

Aged↗
PubMed1993

The post-operative gonadotropin level in post-menopausal women with epithelial ovarian cancer.

Serial estimates of the post-operative hormone levels were made in 15 women subjected to oophorectomy because of ovarian carcinoma. All women were post-menopausal. Pre-operatively, they had significantly lower follicle stimulating hormone (FSH) levels compared with an age-matched control group. Blood samples were collected after a median time of 8 months (139-378 days). After oophorectomy, significantly higher FSH values were found (P = 0.0002), whereas the luteinizing hormone (LH) values were not significantly changed. The inhibin, estradiol and progesterone values were found to be significantly lowered compared with the pre-operative sample. Total and unbound testosterone levels were significantly lower while dehydroepiandrosterone sulphate (DHEAS) and androstenedione levels were unchanged compared with the original sample and compared with controls. Most likely, estradiol and progesterone are produced by the epithelial malignant tumors, as the post-operative values are completely comparable with the primarily included healthy controls. The FSH is suppressed by inhibin and only to a minor degree by the steroid hormones as indicated by the correlation coefficients. Of great interest is the question whether inhibin production is random, or defensive, lowering the gonadotropin levels or influencing tumor growth in some hitherto unknown fashion.

Aged↗
PubMed1993

Human papillomavirus in vulvar squamous-cell carcinoma and in normal vulvar tissues: a search for a possible impact of HPV on vulvar cancer prognosis.

Paraffin-embedded sections of vulvar squamous-cell carcinomas and of normal vulvar tissues were examined for HPV types 6, 11, 16, 18 and 33 by the polymerase chain reaction. Overall, 19 of 62 tumours harboured HPV DNA of types 16, 18 or 33. HPV types 6 and 11 were not detected. HPV DNA was found in 61% of tumours with adjacent intraepithelial neoplasia (VIN III), and in 13% of tumours without associated VIN III. HPV DNA was not detected in any of 101 normal vulvar tissues. HPV DNA was found more often in younger women, in patients with VIN III-associated tumours, and in those with multicentric anogenital neoplasia. This points to the existence of a subset of vulvar carcinomas preceded by intraepithelial neoplasia, with HPV as a major factor in carcinogenesis. HPV also seems to be an important factor in the development of multiprimaries in these patients. The 2 groups of patients with vulvar carcinoma did not differ with regard to prognosis, as estimated by the risk of recurrence after primary surgery.

Adult↗
PubMed1993

Cervical koilocytosis and high risk HPV types: the benefit of laser vaporization.

Forty-six patients with biopsy-proven cervical koilocytosis, which in 19 cases was associated with CIN I, were randomized to treatment by cervical laser vaporization or to follow-up without therapy. The polymerase chain reaction was used to examine the paraffin-embedded cervical biopsies for human papillomavirus (HPV) types 6, 11, 16, 18 and 33 by polymerase chain reaction and molecular hybridization technique. Twenty biopsies contained HPV DNA, in 17 cases of the putatively oncogenic types HPV 16 and HPV 18. During a mean follow-up of 28 months, the lesions resolved in 37 women, 5 women had progression to CIN III lesions, and 4 women had persisting disease. Lesions not harboring any of the 5 HPV types showed a high spontaneous regression rate of 88%, which was not improved by the laser therapy. In the HPV-positive lesions, resolution occurred in only 29% of untreated lesions, but in 92% of those treated by laser. The difference is significant (P = 0.007). It is concluded that in patients with cervical koilocytosis, the HPV diagnosis could be of practical value in identifying patients who might benefit from treatment.

Adult↗
PubMed1993

Hormonal factors and prognosis in epithelial ovarian cancer: a multivariate analysis.

When a significantly lower follicle stimulating hormone (FSH) level was found in patients with epithelial ovarian carcinoma, it was decided to analyze the influence of hormonal factors on prognosis. Thirteen factors were tested for prognostic significance in 35 women with epithelial ovarian carcinoma. Age, FIGO-stage, histopathological grade, residual tumor, treatment, gonadotrophins and steroid hormones were tested. By univariate log-rank testing a significantly shorter survival time was found for patients with ascending FIGO-stage, residual tumor mass, estradiol < 0.10 nmol/l, progesterone < 2.0 nmol/l and DHEAS < 1300 nmol/l. In the Cox model the independently significant prognostic factors found were residual tumor mass (P < 0.001) with a risk estimate of 2.65, progesterone (P < 0.05) with a risk estimate of 0.29 for a progesterone level > 2.0 nmol/l and total testosterone (P < 0.03) with a risk estimate of 0.29 for a total testosterone level > 1.15 nmol/l. The present findings, together with the assumption that an elevated gonadotrophin level may induce ovarian tumor growth (the gonadotrophin theory), earlier findings of estrogen and progesterone receptors in human ovarian cancer, and the in vitro demonstration of gonadotrophin-growth-stimulation of human malignant epithelial tumors, justify a thorough investigation of the interaction between steroid hormones and receptors, gonadotrophins, tumor bulk and survival in future research protocols.

Adenocarcinoma↗