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Biomedical subjects

M W van den Brekel

Publications and source records attributed to M W van den Brekel.

At least 19 recordsLinked to original sources
PubMed2001

Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas.

High-risk human papillomaviruses (HPVs) have been proposed to be associated with a subset of head and neck cancers (HNSCCs). However, clear biological evidence linking HPV-mediated oncogenesis to the development of HNSCC is hardly available. An important biological mechanism underlying HPV-mediated carcinogenesis is the inactivation of p53 by the HPV E6 oncoprotein. In the present study we investigated this biological relationship between HPV and HNSCC. In total 84 HNSCC tumors were analyzed for the presence of high-risk HPV nucleic acids by DNA polymerase chain reaction-enzyme immunoassay (PCR-EIA) and E6 reverse transcriptase (RT)-PCR as well as for the presence of mutations in the p53 gene. We found 20/84 HPV16 DNA-positive cases with one or more DNA assays, 10 of which were consistently positive with all assays. Only 9/20 cases showed E6 mRNA expression, indicative for viral activity. Only these nine E6 mRNA-positive cases all lacked a p53 mutation, whereas both the other HPV DNA-positive and HPV-DNA negative tumors showed p53 mutations in 36% and 63% of the cases, respectively. Moreover, only in lymph node metastases of HPV E6 mRNA-positive tumors both viral DNA and E6 mRNA were present. Our study provides strong biological evidence for a plausible etiological role of high-risk HPV in a subgroup of HNSCC. Analysis of E6 mRNA expression by RT-PCR or alternatively, semiquantitative analyses of the viral load, seem more reliable assays to assess HPV involvement in HNSCC than the very sensitive DNA PCR analyses used routinely.

Adult↗
PubMed2001

Head and neck squamous cell carcinoma: US-guided fine-needle aspiration of sentinel lymph nodes for improved staging--initial experience.

Ultrasonography (US)-guided fine-needle aspiration with cytologic examination was combined with lymphoscintigraphy for the identification of sentinel lymph nodes (SLNs) in 12 patients with a squamous cell carcinoma of the oral cavity or oropharynx. Dynamic lymphoscintigraphy and a hand-held gamma probe were used to depict the SLNs to be aspirated. Cytologic examination of the aspirated SLNs revealed neck lymph node status in patients who underwent neck dissection (n = 6). In patients who underwent only transoral excision, one false-negative cytologic result was observed. This combined approach is expected to improve the detection of occult neck lymph node metastases.

Aged↗
PubMed2000

Lymphoscintigraphy and ultrasound-guided fine needle aspiration cytology of sentinel lymph nodes in head and neck cancer patients.

Accurate staging of the regional lymph nodes is crucial for the appropriate management of patients with squamous cell carcinoma of the head and neck (HNSCC). However, the current diagnostic modalities have low accuracy for N0 neck, and even the most optimal procedure, ultrasound-guided fine needle aspiration cytology (USgFNAC), still has a sensitivity of only 42%-73%. In this study we evaluated whether the identification of the sentinel node might improve the selection of lymph nodes for USgFNAC. Twelve HNSCC patients received 3-4 peritumoral injections of 10-30 MBq 99mTc-labeled colloidal albumin, and the sentinel node was identified by dynamic scintigraphy and marked on the skin using a handheld probe, and/or by scintillation counting of the aspirates. After sentinel node identification USgFNAC was performed. Correct aspiration of the identified sentinel node(s) was confirmed by scintillation counting. In 11 out of 12 cases the sentinel node(s) could be visualized by dynamic planar imaging. In one case the sentinel node(s) were identified by scintillation counting only. In a number of patients different or supplementary lymph nodes were aspirated on the basis of sentinel node identification. These initial data strongly suggest that sentinel node identification might improve the staging of the neck by USgFNAC.

Biopsy, Needle↗
PubMed2000

Molecular diagnosis of head and neck cancer.

Patients with advanced stages of head and neck cancer frequently develop locoregional recurrence as well as distant metastases. These data indicate that traditional diagnostic methods such as histopathology and radiology are not sensitive enough to detect the small numbers of tumor cells which are left behind, defined as minimal residual disease (MRD). Sensitive diagnostic assays based on molecular markers appear to be powerful tools to improve the staging of these patients. At the DNA level, tumor-specific p53 mutations seem to have great potential for the detection of "occult" tumor cells at surgical margins and lymph nodes. At the RNA level HNSCC associated antigens like the E48 antigen, allow the detection of rare HNSCC cells in blood and bone marrow and, it is hoped, also in lymph nodes and lymph node aspirates. However, the molecular assays which are used to detect MRD are subject to certain (technical) problems which affect their sensitivity and specificity. In this paper we will present examples of molecular assays such as the plaque assay using p53 mutations and the E48 RT-PCR, and show their use for MRD detection in cervical lymph nodes. In addition, we will discuss the problems and pitfalls associated with these sensitive techniques.

Artifacts↗
PubMed2000

Lymph node metastases: CT and MRI.

Imaging is playing a major role in the assessment of cervical lymphadenopathy. In head and neck malignancies, imaging can be helpful for staging, and sometimes in differentiating different types of metastases, such as squamous cell carcinomas, non-hodgkins disease and thyroid carcinomas. This article on imaging of cervical lymph node metastases will describe both radiological and clinical aspects. Computed tomography (CT) and magnetic resonance (MR) are widely used for primary tumor and nodal imaging. However, very seldom these modalities have clinical consequences for the management of the neck, such as a wait-and-see policy if no nodes are depicted. This is caused by the limited accuracy of both modalities caused by the fallibility of radiologic criteria for metastases. Ultrasound (US) is hampered by similar morphologic criteria, and only US-guided fine needle aspiration cytology (FNAC) can offer additional cytologic criteria which are more reliable.

Contrast Media↗
PubMed2000

Molecular assays for the diagnosis of minimal residual head-and-neck cancer: methods, reliability, pitfalls, and solutions.

The prognosis of cancer patients is determined by the radicalness of treatment: residual tumor cells will grow out and develop in manifest local recurrences, regional recurrences, and distant metastases. Classical diagnostic methods such as radiology and histopathology have limited sensitivities, and only by molecular techniques can minimal residual disease be detected. In tissue samples containing the normal tissue counterpart of a tumor, only tumor-specific markers can be exploited, whereas in other samples, tissue-specific markers can be used. At present, there are two main methodologies in use, one based on antigen-antibody interaction and the other based on amplified nucleic acids. The most commonly used nucleic acid markers are mutations or alterations in tumor DNA (tumor-specific markers) or differentially expressed mRNA (tissue-specific markers). Many reports and reviews have been published on the assessment of minimal residual disease by molecular markers, showing either positive or negative clinical correlations. One of the main reasons for these contradictory findings is the technical difficulty in finding the small numbers of tumor cells in the large number of normal cells, which necessitates sensitivities of the assays up to 1 tumor cell in 2 x 10(7) normal cells. These assays often are complex, demand considerable experience, and usually are laborious. In this review, we will address a number of the technical issues related to molecular assays for tumor cell detection that make use of nucleic acids as markers. Many difficulties in data interpretation are at least in part because of technical details that might have been solved by the incorporation of one or more appropriate controls. We hope that this review clarifies a number of these issues and help clinicians and investigators interested in this field to understand and weigh the contradictory findings in the published studies. This will help move the field forward and facilitate clinical implementation.

Biomarkers, Tumor↗
PubMed1999

[Patient with a parapharyngeal cyst].

In a 34-year-old woman a parapharyngeal mass was found which led to snoring, apnoeas, a feeling of pressure in the pharynx and paraesthesias around the mouth. MRI imaging showed a parapharyngeal mass, most likely a cyst. Patient underwent excision of the mass via an external approach. Histological examination confirmed the parapharyngeal cyst. The literature is inconclusive as to the origin of such cysts. They might be a relic of the 2nd branchial sac, they might be causally related to the cervical sinus of His, they might be a relic of the connection between the thymus and the 3rd branchial pouch, or they might represent cystic differentiation of epithelium found in lymphoid tissue. MRI or CT is of great importance for information on the anatomical relation of the cyst with the great vessels and other surrounding structures. Excision via external approach is possible but transoral excision with or without mandibulotomy is also an option.

Adult↗
PubMed1999

Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P<.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

Adolescent↗
PubMed1999

Outcome of observing the N0 neck using ultrasonographic-guided cytology for follow-up.

OBJECTIVE: To assess the outcome of patients who underwent transoral tumor excision and a wait-and-see policy for the NO neck, using ultrasonographic-guided fine-needle aspiration cytology (US-FNAC) of the neck for both selecting patients for neck treatment or observation and for follow-up. DESIGN: Retrospective outcome analysis of a patient cohort without palpable or US-FNAC detectable nodal metastases undergoing transoral tumor excisions. Patients were followed up for 1 to 4 years using palpation and US-FNAC. SETTING: Academic center. PATIENTS: A consecutive sample of 77 patients mainly with oral carcinomas. Excluded were patients who had neck dissections, radiotherapy, or no US-FNAC during follow-up. INTERVENTION: Transoral tumor excision. Neck dissection with radiotherapy for regional failure. OUTCOME MEASURE: The recurrence rate in the neck, without failure at the primary site and the salvage rate of these neck recurrences were the most important measures. Treatment delay and histopathologic findings were assessed as well. RESULTS: Fourteen patients (18%) had occult lymph node metastases and neck failures. Of the 14 neck failures, 9 were detected within 7 months of which 6 were not palpable. Ten (71%) of these 14 patients were successfully salvaged, and 4 died of uncontrolled disease. Three of the 4 patients also had distant metastases. CONCLUSIONS: The low recurrence rate (18%) can be attributed to the initial US-FNAC. The high salvage rate (71%) indicates that strict US-FNAC follow-up enables early detection of recurrence in the neck. A wait-and-see policy thus seems warranted, provided regular US-FNAC examinations during follow-up can be guaranteed.

Adult↗
PubMed1999

Radiologic evaluation of neck metastases: the otolaryngologist's perspective.

Imaging of the neck for the assessment of nodal metastases can be used to detect occult metastases or to assess operability of palpable metastases. The detection of small occult metastases has limitations, as micrometastases cannot be depicted. However, imaging can diminish the risk of occult metastases and thus influence management; for this purpose a very sensitive technique is necessary. The currently used radiologic criteria are not sensitive enough to accomplish enough reduction in the risk of occult metastases. Therefore, more sensitive CT and MRI criteria, but especially ultrasound guided aspiration, should be used to assess the clinically negative neck.

Head and Neck Neoplasms↗
PubMed1999

Sonographically guided aspiration cytology of neck nodes for selection of treatment and follow-up in patients with N0 head and neck cancer.

BACKGROUND AND PURPOSE: The management of the clinically negative neck (NO) remains controversial because the incidence of occult metastases is high and the prognostic difference between elective treatment and a "wait and see" approach remains unclear. This study was undertaken to assess the role of sonographically guided aspiration cytology for the selection of the initial-management strategy for the neck and for the early detection of neck metastases during follow-up of patients with NO. METHODS: Seventy-seven clinically and cytologically confirmed NO patients, who underwent a transoral tumor excision and no neck treatment, were followed up for 1 to 4 years by both palpation and sonographically guided aspiration cytology. RESULTS: Fourteen patients (18%) had recurrent neck tumor; 10 (71%) of these necks were salvaged. Of the 14 neck failures, six were detected before being palpable and nine were detected within 7 months. Eleven of the 19 aspirated tumor-positive nodes had a minimal diameter smaller than 1 cm, and all four patients who eventually died had lymph node metastases larger than 14 mm. CONCLUSION: With sonographically guided aspiration cytology, the risk of missing occult metastases was 18%, which is less than expected after palpation only. Sonographically guided aspiration cytology is an effective technique for following up on the status of the neck after transoral tumor excision, and should be used at frequent intervals if no elective neck treatment is performed.

Adult↗
PubMed1998

[Tuberculosis of the larynx].

Laryngeal tuberculosis was diagnosed in two men, a 73-year-old man Dutch by birth and a 40-year-old one Turkish by birth. In the former patient it was probably primary tuberculosis, in the latter secondary (he had lung tuberculosis as well). The clinical picture was highly suggestive of laryngeal carcinoma in both patients. They both recovered with chemotherapy. Laryngeal tuberculosis may mimic laryngeal carcinoma. The diagnosis is based on Ziehl-Neelsen staining, culture and polymerase chain reaction (PCR) on Mycobacterium tuberculosis. Because laryngeal tuberculosis is highly infectious, the patient has to be nursed in isolation and people in his or her environment have to be screened. The response of laryngeal tuberculosis to chemotherapy is good.

Adult↗
PubMed1998

The impact of tumour volume and other characteristics on uptake of radiolabelled monoclonal antibodies in tumour tissue of head and neck cancer patients.

Radioimmunotherapy (RIT) seems to be a realistic option for eradication of minimal residual squamous cell carcinoma of the head and neck (HNSCC), although uptake levels of radiolabelled monoclonal antibodies (MAbs) in tumour tissue vary strongly. The aim of this study was to obtain greater insight into the factors influencing the accumulation of MAbs in HNSCC. Twenty-seven HNSCC patients were injected with radiolabelled MAb E48 or U36 and underwent surgery 2 days after injection. Radioactivity was measured in tumour biopsies taken from the surgical specimen. Uptake levels were correlated with various patient, tumour and MAb characteristics, including age, sex, site, TNM stage, volume as assesssed by computed tomography or magnetic resonance imaging, degree of differentiation, antigen expression of the tumour, the particular MAb that had been injected and the MAb dose. A stepwise regression multivariate analysis showed that tumour volume is the most significant prognostic factor (P=0. 01) for MAb uptake. In conclusion, a significantly higher MAb uptake is found in small tumours as compared to larger tumours. Therefore, RIT may be particularly effective in head and neck cancer patients when used in an adjuvant setting.

Aged↗
PubMed1998

Assessment of tumour invasion into the mandible: the value of different imaging techniques.

In oral carcinomas close to the mandible, tumour invasion of the mandible is important in selecting segmental or marginal resection. Imaging may play a role in assessing tumour invasion. This study compares the accuracy of panoramic X-ray, CT and MR imaging in assessing invasion of the mandible in 29 patients. At histopathology, 6 patients had mandible erosion, 12 had invasion and 11 had an intact mandible. Magnetic resonance imaging had the highest sensitivity (94%), but a low specificity (73%), with 3 of 11 intact mandibles interpreted as positive. Furthermore, MR often overestimated the extent of tumour invasion. On the other hand, CT and panoramic X-ray had a lower sensitivity (64 and 63%, respectively) and a higher specificity (89 and 90%, respectively). Computed tomography (using 5-mm sections) and panoramic X-ray had a similar accuracy, and negative findings do not exclude invasion. Magnetic resonance imaging was the most sensitive technique but had more false positives and frequently overestimated the extent of tumour invasion. Because none of the radiological techniques are accurate enough, clinical examination seems at present to remain the most important modality in deciding between segmental and marginal resection. Tumour invasion at CT or panoramic X-ray is a strong argument for a segmental resection.

Adult↗