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Biomedical subjects

S Daugaard

Publications and source records attributed to S Daugaard.

At least 19 recordsLinked to original sources

Soft tissue sarcomas of the head and neck: a single-centre experience.

OBJECTIVE: The aim of this study was to report our experience with malignant and borderline soft tissue tumours (STS) of the head and neck region in the period 1977-2000. DESIGN: Retrospective case study including new evaluation of histological specimens. SETTING: Tertiary centre, single centre. PARTICIPANTS: Review of patient's records and new evaluation of pathological specimens were made for 66 patients. After evaluation only 36 patients (26 men and 10 women) still met present criteria for a STS in head and neck in adults. RESULTS: The original histological diagnosis was changed in 27 (41%) of the 66 patients with a primary diagnosis of sarcoma. After review the most common histological diagnoses were leiomyosarcoma (5) and rhabdomyosarcoma (5). Overall 5-year survival rate was 60%. Overall 5-year disease-free survival rate was 44%. The study showed that both tumour grade and surgical margin had a statistically significant impact on survival. No relation was found between survival and tumour size or age. CONCLUSION: The grave prognosis especially for high-grade tumours emphasizes the need for improved treatment strategies. Furthermore, conclusions from older studies concerning prognosis may be obsolete as approximately 40% of tumours previously diagnosed as sarcomas may be invalid by present day standards.

Disease-Free Survival↗

Current soft-tissue sarcoma classifications.

In order to analyse the impact of modern sarcoma classification criteria, pathological material from 281 extremity soft-tissue sarcomas (STS) was reviewed. The cases were originally diagnosed between 1972 and 1994, and the most frequent diagnoses then were malignant fibrous histiocytoma (MFH) (26%), liposarcoma (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the proportions had changed significantly, with the largest group now being leiomyosarcomas (20%), liposarcomas (17%), synovial sarcomas (14%), and sarcomas "not otherwise specified" (NOS) (11%). The original diagnosis was changed in 57% of the cases; in particular, the number of fibrosarcomas was reduced from 32 to 6, and MFHs from 72 to 2, with 22 renamed as myxofibrosarcomas; 20 (7%) were found not to be sarcomas. The main reasons for these results are the recent advances in immunohistochemistry (IHC) together with changes in nomenclature. The findings have obvious implications, in particular for retrospective research.

Fibrosarcoma↗

Ossifying fibromyxoid tumour of soft parts, with focus on unusual clinicopathological features.

AIMS: Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the soft tissues of proximal limbs/girdle, or head and neck. Histologically, it usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid matrix with a characteristic peripheral ossification. However, we present two cases that deviated from this pattern. MATERIAL AND METHODS: One tumour, which was removed from the axilla of a 55-year-old female, was unusual in its large size (120 mm in diameter) and in its restriction of bone formation to its central zones. The other tumour, which occurred in a 62-year-old female, was remarkable in its acral location on the hand and high mitotic activity (four mitoses per high-power field). These features caused concern and follow-up of the patients was recommended. So far there have been no recurrences (25 and 18 months after surgery, respectively). An additional previously undescribed feature was the presence of fibronexus-like structures by electron microscopy in the second case. However, a myofibroblastic phenotype was not supported by the immunohistochemical findings. CONCLUSION: Though a distinct entity, ossifying fibromyxoid tumour may exhibit a wider clinicopathological spectrum than generally recognized.

Biomarkers, Tumor↗

High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group.

The activity and toxicity of single-agent standard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin. A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received (A) doxorubicin 75 mg m(-2) on day 1 (112 patients), (B) epirubicin 150 mg m(-2) on day 1 (111 patients) or (C) epirubicin 50 mg m(-2) day(-1) on days 1, 2 and 3 (111 patients); all given as bolus injection at 3-week intervals. A median of four treatment cycles was given. Median age was 52 years (19-70 years) and performance score 1 (0-2). Of 314 evaluable patients, 45 (14%) had an objective tumour response (eight complete response, 35 partial response). There were no differences among the three groups. Median time to progression for groups A, B and C was 16, 14 and 12 weeks, and median survival 45, 47 and 45 weeks respectively. Neither progression-free (P = 0.93) nor overall survival (P = 0.89) differed among the three groups. After the first cycle of therapy, two patients died of infection and one owing to cardiovascular disease, all on epirubicin. Both dose schedules of epirubicin were more myelotoxic than doxorubicin. Cardiotoxicity (> or = grade 3) occurred in 1%, 0% and 2% respectively. Regardless of the schedule, high-dose epirubicin is not a preferred alternative to standard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas.

Adult↗

Adenocarcinoma of the cervix and adenocarcinoma of the endometrium: distinction with PCR-mediated detection of HPV DNA.

The differential diagnosis between primary endocervical adenocarcinoma and adenocarcinoma originating in the endometrium may in some cases be difficult. The two cancer types have a different genesis, with human papillomavirus (HPV) as an important causal factor in the development of primary cervical carcinoma. In this study, the paraffin-embedded cervical tissues from 23 patients with stage II endometrial carcinoma and from 50 patients with primary cervical adenocarcinoma were examined for HPV DNA of types 16, 18, and 33. HPV DNA was demonstrated in 70% of the primary endocervical adenocarcinomas and in none of the endometrial carcinomas. It is concluded that HPV detection may be useful in the differential diagnosis of some cases of cervical and endometrial adenocarcinoma.

Adenocarcinoma↗

Human papillomaviruses and multifocal genital neoplasia.

In 143 patients with vulvar carcinoma (76 cases) or vulvar intraepithelial neoplasia (VIN III, 67 cases), cervical cancer or cervical intraepithelial neoplasia CIN III lesions developed in 39 patients (27%) at some time during their life. In patients with classic keratinizing squamous cell carcinoma (KSC) of the vulva, cervical neoplasia developed in only one of 51 (2%), whereas the frequency was 10 of 25 (40%) in patients with vulvar carcinoma of the basaloid or warty type and 28 of 67 (42%) in patients with VIN III lesions. The original, paraffin-embedded surgical specimens were examined by polymerase chain reaction and type-specific molecular hybridization for human papillomavirus (HPV) DNA of the types 6, 11, 16, 18, and 33. DNA of the oncogenic types HPV 16 or HPV 33 was found in 4% of the KSCs, in 84% of the basaloid or warty carcinomas, in 90% of VIN III lesions, and in 89% of the cervical lesions. The same HPV type was found in both lesions in 81% of the patients with double primary tumors. The results support the concept that VIN III and a subgroup of vulvar carcinomas are HPV-related lesions, that they are frequently associated with another HPV-related genital primary tumor, and that these multiprimary tumors are secondary to an HPV infection involving the entire genital tract.

Adult↗

Imaging of chondrosarcoma with histopathological and prognostic correlation. An analysis of 49 cases mainly based on plain film radiography.

PURPOSE: To investigate the course of chondrosarcoma in relation to radiographic and histopathologic findings. MATERIAL AND METHODS: 49 consecutive patients seen during an 11-year-period were analysed, including re-evaluation of their radiographic and histopathologic material. RESULTS: Forty-two patients had radiographic changes typical for cartilaginous tumours, in 37 with malignant stigmata. Seven patients had malignant changes not typical for chondrosarcoma. By histopathologic grading 16 patients had grade I, 17 grade II and 16 grade III tumours. Six of the grade II-III tumours were histopathologic variants (mesenchymal, dedifferentiated or myxoid chondrosarcomas). Surgical removal of the tumour was performed in 42 patients, 41 of whom were followed up for 0.4-11.4 years (median 3.8 years). Local recurrence occurred in 7 patients, and 11 patients developed metastases. Ten patients, 4 with local recurrence and metastases, and 6 with metastases only were dead at the end of the follow-up. The actuarial 5-year overall survival rate was 64%. The occurrence of local recurrence, metastases and death was found to be related to the histopathologic grades II and III. Atypical radiographic features only occurred in grade II-III tumours and were related to metastases and death, but not to local recurrence. CONCLUSION: Atypical radiographic findings were related to high-grade malignancy and poor prognosis.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

Nasopharyngeal carcinoma: histopathological types and association with Epstein-Barr Virus.

The polymerase chain reaction was used to examine paraffin-embedded tissues of 37 nasopharyngeal carcinomas (NPC) for Epstein-Barr virus (EBV) genomic sequences. EBV DNA was found in 2/14 keratinising squamous cell (WHO 1) carcinomas and in all of 23 non-keratinising and undifferentiated (WHO 2 and 3) NPC. The study confirms the infrequent association of keratinising NPC and EBV, in contrast with the 100% association of the less differentiated NPCs and the virus. The results may indicate a different carcinogenesis for the WHO 1 NPC subtype.

Carcinoma↗

Histopathological grade and response to chemotherapy in advanced soft tissue sarcomas.

In a retrospective analysis, we evaluated the possible significance of histopathological grade with regard to response to chemotherapy in advanced soft tissue sarcomas. In three EORTC protocols, the same dose-schedule was used for patients randomised to treatment with doxorubicin as a single agent (75 mg/m2 every third week). The submitted pathological slides from 94 of these patients were reviewed and graded. The following parameters were subjectively graded (+/++/+ + +): nuclear pleomorphism, necrosis, cellularity and vascularity. Mitoses were counted in 20 high-power fields, and a final grade assigned as I, II, IIIA or IIIB. The results were tested both with regard to response (complete response + partial response vs. no change + progressive disease) and survival. However, no statistically significant correlations or trends could be demonstrated. Thus, tumour grade, although a prognostic factor by itself, does not seem to be able to predict response to chemotherapy in the advanced stage.

Doxorubicin↗

Human papillomavirus, Epstein-Barr virus, and cervical carcinoma in Greenland.

The incidence of cervical cancer in Greenland is one of the highest in the world. This is in accordance with known epidemiologic risk factors, in particular of sexual lifestyle and tobacco smoking. Yet a recent study of cervical smears from randomly selected Greenlandic women failed to demonstrate any elevated prevalence of human papillomavirus (HPV), of which particularly HPV types 16 and 18 are assumed to play a role in the development of cervical dysplasia and carcinoma. Another oncogenic virus, Epstein-Barr virus (EBV) is known to be widespread in the Greenlandic population and the virus has been reported to infect the female genital tract. We therefore used the polymerase chain reaction to examine paraffin-embedded tissues of cervical carcinomas from 11 indigenous Greenlandic women and, for comparison, also cervical carcinoma tissues from 11 Danish patients, for EBV, HPV 16 and HPV 18 DNA sequences. None of the 22 cervical tissues contained EBV DNA. Six Greenlandic and five Danish carcinomas harbored HPV 16 DNA, and one carcinoma of each group was HPV 18-positive. In conclusion, cervical carcinoma is not associated with EBV infection. Further, the oncogenic HPVs are probably encountered at the same rate in carcinomas from Greenland and from Denmark.

Journal Article↗