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Gedske Daugaard

Publications and source records attributed to Gedske Daugaard.

14 recordsLinked to original sources
PubMed2006

PET/CT imaging in response evaluation of patients with small cell lung cancer.

UNLABELLED: There is an increasing amount of evidence on the usability of PET in response evaluation of non-small cell lung cancer. However, data on SCLC is scarce and mainly retrospective. This prospective study assesses the use of PET (positron emission tomography) and PET/CT in response evaluation of patients with small cell lung cancer (SCLC). METHODS: Assignment of early and final response was compared between PET, PET/CT, and CT in 20 patients with SCLC. Final response as assigned by CT (RECIST) served as reference. RESULTS: At response evaluation after one cycle of chemotherapy major disagreement (responder versus non-responder) between PET and CT in predicting final response was seen in 1 of 12 patients. At final response evaluation major disagreement between PET, PET/CT and CT was seen in 2 of 19 patients (11%). All measurements of FDG-uptake were significantly correlated to size and changes in size as measured by CT. A significant difference in relative change in tumour FDG-uptake and volume was found between responding and non-responding patients. No significant difference was found between a visual and semi-quantitative analysis of PET. CONCLUSION: Response evaluation of SCLC by PET/CT is feasible, but it is uncertain whether it adds further information to evaluation by RECIST, thus further studies and standardization of methods are needed.

Aged↗
PubMed2006

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.

Chromosome Mapping↗
PubMed2006

Inguinal metastases from testicular cancer.

OBJECTIVE: To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease. PATIENTS AND METHODS: Of 695 patients, 14 (2%) with stage I testicular cancer developed inguinal metastases during the follow-up on a surveillance programme. At orchidectomy, one patient had involvement of the tunica albuginea and one a history of cryptorchidism and development of testicular cancer on the contralateral side. The remaining patients had no history of previous surgery in the inguinal region or in the scrotal area, or any other known risk factors for developing inguinal-node metastases. Two patients had a seminoma (0.5%) and 12 (4%) a nonseminoma. The histopathological examination showed that the metastases were in lymph nodes in four patients, the remainder having a more diffuse involvement of the tissue in the inguinal region. At relapse, patients were treated by three or four cycles of bleomycin, etoposide and cisplatin, except those with low-stage seminomas (stage IIa and IIb), who were treated by radiation therapy. RESULTS: All patients had a complete remission after treatment with chemotherapy or radiotherapy. No patients died or developed a recurrence during the median follow-up of 72 months. CONCLUSION: Metastases to the inguinal region are found in approximately 2% of patients with testicular cancer; about a quarter have lymph-node metastases, the rest probably having metastases to the spermatic cord with direct invasion into the surrounding tissue. High ligation of the spermatic cord is therefore important. Chemotherapy for patients with nonseminoma and radiotherapy for patients with seminoma gives excellent results.

Abdominal Neoplasms↗
PubMed2005

The Y deletion gr/gr and susceptibility to testicular germ cell tumor.

Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region--known as the "gr/gr" deletion--has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.

Alleles↗
PubMed2005

Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction.

BACKGROUND: The use of anthracyclines in treatment of cancer is limited by cardiotoxicity of these compounds and may lead to heart failure. Therefore monitoring of cardiac function is necessary during therapy. AIM: We evaluated the value of natriuretic peptides (N-terminal pro-atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP)) for monitoring and predicting anthracycline induced cardiotoxicity using radionuclide left ventricular ejection fraction (EF) measurements as reference. METHODS AND RESULTS: A total of 107 consecutive patients receiving anthracycline as part of their chemotherapy for malignant disease were studied. Plasma concentrations of the peptides were measured by radioimmunoassay and EF by radionuclide cardiography. For reduced EF values, i.e. below 0.50 a fairly strong correlation was found between N-ANP or BNP and EF. Of 48 patients with serial EF and peptide measurements, 19% showed a significant EF decrease (>0.10) and ended with a final EF value below 0.50. Baseline EF was no predictor of a change in EF during treatment. Neither baseline levels of N-ANP or BNP nor a change in the same variables during therapy were predictive of a change in EF. CONCLUSIONS: In spite of correlations between peptide concentrations and reduced EF values neither baseline values nor serial measurements can safely substitute EF monitoring in patients undergoing anthracycline therapy.

Adolescent↗
PubMed2004

Incidence of chemotherapy-induced nausea and emesis after modern antiemetics.

BACKGROUND: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and emesis (vomiting) (CINV) among patients receiving highly (HEC) or moderately (MEC) emetogenic chemotherapy. They also assessed whether physicians and nurses accurately recognized the incidence of acute and delayed CINV in their own practices. METHODS: A prospective, observational study of adult patients receiving HEC or MEC for the first time was performed. Before patient enrollment, medical oncologists and oncology nurses estimated the incidence of acute (Day 1) and delayed (Days 2-5) CINV after first administration of HEC and MEC in their own practices. Eligible patients from their practices then completed a 6-day diary including emetic episodes, nausea assessment, and antiemetic medication use. Observed incidence rates of acute and delayed CINV were compared with physician/nurse predictions. RESULTS: Twenty-four physicians and nurses and 298 eligible patients (67 receiving HEC and 231 receiving MEC) were recruited from 14 oncology practices in 6 countries. Greater than 35% of patients overall experienced acute nausea, whereas 13% experienced acute emesis. Delayed nausea and emesis were observed in 60% and 50% of HEC patients, respectively, and in 52% and 28% of MEC patients, respectively. Delayed symptoms appeared without acute symptoms after HEC (emesis, 38%; nausea, 33%) and MEC (emesis, 19%; nausea, 21%). Physicians and nurses accurately predicted the incidence of acute CINV but underestimated the incidence of delayed nausea and emesis after HEC by 21 and 28 percentage points, respectively, and delayed nausea after MEC by 28 percentage points. Greater than 75% of physicians and nurses underestimated the incidence of delayed CINV after both HEC and MEC. CONCLUSIONS: Physicians and nurses markedly underestimated the incidence of delayed nausea and emesis after both HEC and MEC. Delayed nausea and emesis, which may appear even in the absence of acute nausea and emesis, remain important targets for improved therapeutic intervention.

Adult↗
PubMed2003

Surveillance in stage I testicular cancer.

Treatment results on 695 stage I testicular cancer patients followed with surveillance are described. Seminoma (SGCT) was present in 394 patients and nonseminoma (NSGCT) in 301 patients. Relapses were detected in 155 patients (22%), in 69 patients with SGCT (17%) and 86 with NSGCT (29%). In patients with vascular invasion, relapse was detected in 54% of patients with NSGCT and 38% of patients with SGCT. Time to relapse was median 13 months (range 1 to 84 months) for SGCT and 5 months (range 1 to 171 months) for NSGCT. Forty-nine percent of relapses in SGCT patients were seen within the first year, 87% of the relapses were diagnosed within the first two years, and 98% of the relapses were detected within 5 years. The figures for NSGCT were 80%, 89% and 95%, respectively. Forty-five patients had carcinoma in situ in the contralateral testis, 62% had this together with a seminoma in the other testis. Ten patients died during the follow-up period. None of these deaths were caused by the germ cell tumour or the treatment. The overall survival for patients with stage I disease is 98.6%, and the cause specific survival 100%.

Adolescent↗
PubMed2003

Endocrine function in patients treated for carcinoma in situ in the testis with irradiation.

CIS is found in the contralateral testis in 5% of the patients with testicular germ cell cancer. The management of CIS in the contralateral testis is important because the majority - if not all - cases of CIS will progress to invasive disease without treatment. It is well documented that testicular irradiation with a total dose of 14-20 Gy (2 Gy x 7-10) is an effective and safe treatment for CIS in the contralateral testis in patients with unilateral testicular germ cell cancer. However few relapses of testicular cancer have been observed in testis treated with these regimens and the data on 14 Gy are sparse. One study has indicated that more radiotherapy with lower doses per fraction could be useful, but more data are needed to confirm this. Endocrine testicular function has been shown to be impaired already before treatment in patients with CIS and is further impaired after testicular irradiation with 14-20 Gy (2 Gy x 7-10) and only minor dose dependency is seen in the impairment of Leydig cell function. The optimal treatment of CIS in the contralateral testicle in patients orchidectomised for testicular cancer seems to be local radiotherapy of the testis with CIS in order to preserve at least a part of the Leydig cell function. However, the optimal dose level has to be defined.

Carcinoma in Situ↗
PubMed2003

No AZF deletion in 160 patients with testicular germ cell neoplasia.

Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associated with a relative reduction of Y chromosomal material (e.g. 45,X/46,XY) or other abnormalities of the Y chromosome. The euchromatic long arm of the human Y chromosome (Yq11) contains three azoospermia factors (AZFa, AZFb, AZFc) functionally important in human spermatogenesis. Microdeletions encompassing one of these three AZF loci result in the deletion of multiple genes normally expressed in testis tissue and are associated with spermatogenic failure. The aim of our study was to investigate whether AZF microdeletions, in addition to causing infertility, predispose also to germ cell neoplasia, since subjects with poor spermatogenesis have an increased risk of testicular cancer. We screened for putative deletions of AZF loci on the Y chromosome in DNA isolated from white blood cells of 160 Danish patients with testicular germ cell neoplasia. Interestingly, although AZF microdeletions are found frequently in patients with idiopathic infertility, in all cases studied of testicular germ cell cancer the Yq region was found to be intact. We conclude that the molecular aetiology of testicular germ cell neoplasia of the young adult type most likely does not involve the same pathways as male infertility caused by AZF deletions. Malignant transformation of germ cells is thus caused by the dysfunction of some other genes that still need to be identified.

Adult↗
PubMed2002

Analysis of the polymorphic CAG repeat length in the androgen receptor gene in patients with testicular germ cell cancer.

Changes in the length of a polymorphic trinucleotide (CAG) repeat in the androgen receptor (AR) gene, which may lead to altered transactivation of the AR gene, have been implicated to play a role in the pathogenesis of several forms of endocrine cancer and certain reproductive disorders. Subjects with reproductive disorders that are associated with a relative deficiency of androgen function carry an increased risk for testicular cancer, therefore we have examined the (CAG)n in the AR gene in DNA isolated from peripheral blood cells of 102 patients diagnosed with testicular germ cell neoplasia and compared them with a control group of 110 healthy men with proven fertility. All patients and control subjects underwent comprehensive andrological examination that included reproductive hormone profiles and the analysis of the (CAG)n in the AR gene that was done by means of PCR and DNA sequencing. There was no difference in the distribution of (CAG)n between the subjects and controls, no association of (CAG)n and the tumor type and no association with severity of the disease. We conclude that the high risk of testicular germ cell cancer in the Danish population is not associated with the (CAG)n polymorphism in the AR gene.

Adult↗
PubMed2002

Clinical use of serum TRA-1-60 as tumor marker in patients with germ cell cancer.

TRA-1-60 antigen has been related to the presence of embryonal germ cell carcinoma (EC) and carcinoma in situ. Our study further investigated the clinical efficacy of TRA-1-60 as a serum tumor marker for germ cell cancer in the testis. Three groups of patients with germ cell tumors were included: Group 1, 34 patients with disseminated disease (24 nonseminomatous germ cell tumors [NSGCT] and 10 seminomatous germ cell tumors [SGCT]); this group of patients were followed during the course of chemotherapy with measurements of TRA-1-60, HCG and AFP; Group 2, 28 patients with Stage I NSGCT (22 with embryonal carcinoma [EC]-component and 6 without EC-component, median follow-up 15 months); and Group 3, 40 patients with Stage I pure SGCT (median follow-up 15 months). Seventy-eight percent of patients with disseminated EC-positive NSGCT had increased levels of TRA-1-60 before chemotherapy. After chemotherapy, levels of TRA-1-60 had dropped significantly (p < 0.01). Levels of TRA-1-60 did not normalize in 15% of NSGCT and 30% of SGCT patients after chemotherapy. This was not associated with recurrent disease. Approximately one-third of patients with Stage I NSGCT had increased values of TRA-1-60 during follow-up without having a relapse. Contrary to earlier reports TRA-1-60 is not at present useful as a tumor marker in patients with germ cell tumors. Although detecting a few early relapses the rate of false positive elevations in the tumor marker makes it unreliable in the clinical setting. Our study did confirm that elevated levels of TRA-1-60 were present in approximately 80% of patients with disseminated EC-positive NSGCT before start of chemotherapy and chemotherapy induced a significant decrease in levels of TRA-1-60. Thus, the TRA-1-60 antigen might still prove clinically useful provided that the reliability of the assay can be increased.

Antigens, Neoplasm↗
PubMed2002

Effect of graded testicular doses of radiotherapy in patients treated for carcinoma-in-situ in the testis.

PURPOSE: To determine the effect of radiotherapy in doses 14 to 20 Gy on eradication of carcinoma-in-situ (CIS) testis and on the Leydig cell function. PATIENTS AND METHODS: Forty-eight patients presented with unilateral testicular germ cell cancer and CIS of the contralateral testis. The CIS-bearing testis was treated with daily irradiation doses of 2 Gy, 5 days a week, to a cumulative dose of 20 Gy (21 patients), 18 Gy (three patients), 16 Gy (10 patients), and 14 Gy (14 patients). RESULTS: All patients treated at dose levels 20 Gy to 16 Gy achieved histologically verified complete remission without signs of recurrence of CIS after an observation period of more than 5 years. One of 14 patients treated at dose level 14 Gy had a relapse of CIS 20 months after irradiation. Leydig cell function was examined before and regularly after radiotherapy in 44 of 48 patients. The levels of testosterone were lower after radiotherapy than before. Testosterone showed a stable decrease for more than 5 years after treatment (3.6% per year) without dose dependency. The levels of luteinizing hormone and follicle-stimulating hormone were increased after radiotherapy. The need of androgen substitution therapy was similar at all dose levels. CONCLUSION: Testicular irradiation is a safe treatment at dose level 20 Gy (10 x 2 Gy). Decrease of dose to 14 Gy (7 x 2 Gy) might lead to risk of relapse of CIS. Impairment of hormone production without clinically significant dose dependency is seen in the dose range 14 to 20 Gy.

Adult↗
PubMedDate not supplied

CDH1 (E-cadherin) in testicular germ cell neoplasia: suppressed translation of mRNA in pre-invasive carcinoma in situ but increased protein levels in advanced tumours.

E-cadherin (CDH1) is a transmembrane glycoprotein involved in cellular adhesion. In our recent microarray studies of testicular germ cell tumours (TGCTs) and the common precursor carcinoma in situ (CIS), CDH1 mRNA was highly expressed in CIS and embryonal carcinoma. It has previously been reported that the CDH1 protein is not expressed in CIS. To resolve the discrepancy, we performed a detailed analysis of the expression of CDH1 mRNA and protein in a series of normal and neoplastic testes. High expression of CDH1 mRNA in CIS was confirmed by real-time PCR and in situ hybridisation. At the protein level, however, CDH1 was only detected with one of three tested antibodies, but Western blotting analysis with this antibody showed additional bands, suggesting unspecific staining. The levels of a CDH1 protein fragment in serum samples from 58 patients with TGCTs were analysed by ELISA; we found significantly higher levels in patients with advanced disease (stage II/III) when compared to healthy individuals and patients with stage I TGCT. In conclusion, despite high mRNA levels, the CDH1 protein is not expressed in CIS, suggesting translational suppression of CDH1 protein expression. CDH1 serum levels may be a serological marker for staging of TGCT patients.

Adult↗