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Biomedical subjects

R de Bree

Publications and source records attributed to R de Bree.

11 recordsLinked to original sources

[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

Teratoma in a newborn: an unusual cause of airway obstruction.

We report the case of a newborn girl who presented with an inspiratory stridor and apneic episodes due to a mass in the oropharynx. On flexible pharyngo-laryngoscopy, it appeared that on inspiration this swelling, originating from the oropharynx, was sucked into the larynx, obstructing the airway. After intubation under flexible optic control the swelling was excised using the CO2-laser. Histopathological examination showed a teratoma of the oropharynx. The postoperative course was uneventful. Teratomas of the oropharynx are rare and are treated by surgical excision. If respiratory distress accompanies the lesion, priority must be given to securing the airway.

Airway Obstruction

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

Malignant lymphoma of mucosa-associated lymphoid tissue in the larynx.

A 36-year-old woman was referred to the department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, because of complaints of hoarseness. A submucosal swelling of the right ventricular fold was found that was subsequently biopsied. Histopathological examination showed a low-grade B-cell non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT). Treatment consisted of local radiotherapy (to 2800 cGy). During the 2-year follow-up to date there has been no evidence of recurrent disease. To our knowledge, only four cases of MALT lymphomas in the larynx have been reported. The clinical behavior of MALT lymphoma is clearly quite distinct and requires proper recognition to prevent inadvertent misdiagnosis of overtreatment.

Adult

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients.

Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 +/- 0.3 and 11.1 +/- 0.2 mg (n = 5) or 51.1 +/- 0.1 and 51.0 +/- 0.4 mg (n = 5) of both mE48 IgG and mU36 IgG labelled with 131I and 125I simultaneously and underwent surgery 7-8 days after injection. The mean uptake of iodine-labelled mE48 IgG and mU36 was highest in tumour tissue, 8.9 +/- 8.9 and 8.2 +/- 4.4 %ID kg(-1) respectively. Tumour to non-tumour ratios for oral mucosa, skin, muscle, blood and bone marrow aspirate were 2.5, 5.5, 25.2, 4.7 and 4.0 respectively in the case of mE48 IgG and 2.3, 4.1, 21.0, 5.8 and 5.8 respectively in the case of mU36 IgG. The distribution of mMAbs E48 and U36 throughout tumours that had been collected in previous studies was heterogeneous when administered at a dose of 1 or 12 mg, and homogeneous when administered at a dose of 52 mg. Administration of mE48 IgG (1-52 mg) resulted in a human anti-mouse antibody response in 12 out of 28 patients, while for mU36 IgG (1-52 mg), this figure was three out of 18 patients. cMAb E48 was shown to be highly effective in mediating antibody-dependent cellular cytotoxicity in vitro, while cMAb U36 and mMAbs E48 and U36 were not effective at all. Rationales are provided that give priority to the start of adjuvant radioimmunotherapy trials with 186Re-labelled cMAb U36 IgG in head and neck cancer patients who are at high risk for the development of locoregional recurrences and distant metastases.

Animals

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab')2 in patients with head and neck cancer.

Biodistribution and pharmacokinetics of radiolabeled mAb E48 IgG and E48 F(ab')2 were analyzed and compared in 39 patients with histologically proven squamous cell carcinoma of the head and neck who were included in a radioimmunoscintigraphy study and underwent surgery 44 h after injection. Three groups of patients were distinguished: group 1 (n = 19) received technetium-99m (99mTc)-labeled E48 F(ab')2, group 2 (n = 9) received 99mTc-labeled E48 IgG, and group 3 (n = 11) received 99mTc- and 131I-labeled E48 IgG as well as 125I-labeled F(ab')2. Two patients in group 1 and four patients in group 3 received a high mAb dose (10-50 mg), while all other patients received a low mAb dose (1-4 mg). From all patients in groups 2 and 3 biopsies from the surgical specimen were obtained 44 h postinjection. Tumor uptake of 99mTc-labeled E48 IgG was high, ranging from 0.007 to 0.082% of the injected dose/g, with a mean of 0.031 +/- 0.020% of the injected dose/g. The mean tumor:nontumor ratio of this conjugate was 2.8 for mucosa, 4.6 for bone marrow aspirate, 4.1 for blood, 20.3 for fat, and 21.0 for muscle. Activity uptake in tumor positive lymph nodes was 4.7 times higher as compared to negative lymph nodes. Sixteen h postinjection radioimmunoscintigraphy revealed activity uptake in the primary tumor, lymph node metastases, oral cavity, and adrenal glands. Using regions of interest, the uptake in the adrenal glands was estimated to be 0.050% of the injected dose/g. If a high mAb dose was used, no adrenal glands were visualized and the uptake in the oral cavity was clearly diminished, while the tumor uptake and tumor:nontumor ratios were increased. The mean elimination half-lifes t1/2 alpha and t1/2 in plasma were: for E48 IgG (n = 20) 6.6 +/- 2.6 and 54.1 +/- 24.3 h and for E48 F(ab')2 (n = 19) 2.3 +/- 0.4 and 19.9 +/- 4.6 h, respectively. Tumor uptake of 131I-labeled E48 IgG was 49% higher than of 125I-labeled F(ab')2. For most tissues except normal oral mucosa, tumor:nontumor ratios were slightly higher for F(ab')2 than for IgG. The present study shows that mAb E48 accumulates selectively and to a high level in head and neck squamous cell carcinoma. Although no definite conclusions can be drawn as to which mAb form is more suitable, IgG or F(ab')2, mAb E48 seems to have potential for radioimmunotherapy in head and neck squamous cell carcinoma patients.

Adrenal Glands

Radioimmunoscintigraphy and biodistribution of technetium-99m-labeled monoclonal antibody U36 in patients with head and neck cancer.

So far, mAb E48 is the most promising antibody described for specific targeting of head and neck squamous cell carcinoma (HNSCC) in patients. On the basis of its more homogeneous reactivity pattern on HNSCC, the novel mAb U36 may be even better suited for targeting. In this study the biodistribution of mAb U36 was evaluated by radioimmunoscintigraphy (RIS) and biopsy measurements in 10 patients who were suspected of having neck lymph node metastases from a histologically proven HNSCC and who had been scheduled to undergo resection of the primary tumor and neck dissection. Patients received 1.8-53.0 mg mAb U36 IgG labeled with 756 +/- 95 MBq technetium-99m i.v. Preoperatively, palpation, computerized tomography, magnetic resonance imaging, and RIS were performed. RIS images included planar and single-photon emission computerized tomography images of the head and neck and planar images of the whole body. The diagnostic findings were recorded per side as well as per lymph node level of the neck and compared to the histopathological outcome. Radioactivity in blood samples and biopsies from the surgical specimens were measured. All 10 primary tumors were visualized by RIS. All diagnostic modalities were correct in 7 of 14 tumor-involved lymph node levels. The missed lymph node metastases comprised micrometastases, small tumor-involved nodes (<9 mm), and tumor-involved nodes with much necrosis, keratin, or fibrin. There were no false-positive observations with mAb U36. Besides activity uptake in tumor tissue, only a slight accumulation of activity was observed in the mouth, lungs, liver, spleen, kidneys, and scrotal area. Biopsies from the surgical specimen showed a high tumor uptake of 20.4 +/- 12.4% of the injected dose/kg (range, 8.0-43.0% of injected dose/kg), 44 h postinjection. An increase in the mAb dose did not influence uptake of activity in tumor tissue. The mean tumor:nontumor ratio at this time point was 2.3 for mucosa, 2.8 for blood, 3.0 for bone marrow aspirate, 12.9 for fat, and 13.0 for muscle tissue. The present clinical study shows that technetium-99m-labeled U36 IgG accumulates selectively and to a high level in HNSCC. The tumor-targeting results for U36 IgG are comparable to those previously described for E48 IgG. On the basis of the results of ongoing biodistribution studies in which both mAbs E48 and U36, labeled with different iodine isotopes, are simultaneously evaluated for tumor uptake and retention in HNSCC patients, one of these mAbs will be selected for future adjuvant radioimmunotherapy trials.

Aged

Clinical imaging of head and neck cancer with technetium-99m-labeled monoclonal antibody E48 IgG or F(ab')2.

METHODS: In 32 patients who were suspected of having a neck lymph node metastasis from a histologically proven squamous-cell carcinoma of the head and neck (HNSCC), the diagnostic value of 99mTc-labeled (750 MBq) monoclonal antibody (1-2 mg) E48 IgG (n = 17) and its F(ab')2 fragment (n = 15) was evaluated and compared. Preoperative findings on lymph node status obtained by radioimmunoscintigraphy (RIS), computerized tomography (CT), magnetic resonance imaging (MRI) and palpation were defined per side (left and/or right side of the neck) as well as per lymph node level (I through V) and compared to the histopathological outcome of the neck dissection specimen. RESULTS: All 31 tumors at the primary site were visualized. RIS was correct in 201 of 221 levels (accuracy 91%) and in 38 of 47 sides (accuracy 81%). Fifteen levels and seven sides with limited tumor load were scored false-negative and five levels and two sides were scored false-positive. Sensitivity and specificity of RIS were similar to those of palpation, CT and MRI. The diagnostic value of RIS with E48 F(ab')2 or E48 IgG appeared to be similar. CONCLUSIONS: The present study shows that RIS with either E48 F(ab')2 or E48 IgG is as valuable as the other imaging techniques. The selective accumulation of radioactivity in tumor tissues, in combination with the known intrinsic radiosensitivity of HNSCC, justifies the development of radioimmunoconjugates for radioimmunotherapy.

Aged

[Primary adenocarcinoma of the navel after a seemingly harmless discharge of many years' duration].

A woman aged 49 complained of longstanding umbilical discharge. In the floor of the navel a granulomatoid lesion was observed, which histopathologically proved to be a well-differentiated adenocarcinoma. This was thought to be a primary tumour as extensive investigation revealed no other primary tumour. The umbilical area was excised. Colonic malrotation was seen as well as a Meckel's diverticulum. The patient recovered completely.

Abdominal Muscles

[Tungiasis].

Tungiasis is an inflammation of the skin caused by infestation of a fertilised female sand flea, Tunga penetrans. Two patients who contracted this skin disease in the tropics (Surinam and Kenya-Uganda) are described. Because of the increase of international travelling, import diseases are seen more often. If the disease is known, it is easy to diagnose and to treat tungiasis.

Adult

Squamous cell carcinoma-associated antigens used in novel strategies for the detection and treatment of minimal residual head and neck cancer.

The improvement of detection and eradication of minimal residual disease, to reduce local and distant relapse after primary therapy, is one of the major challenges in the management of squamous cell carcinoma of the head and neck (HNSCC). This paper describes perspectives arising from the use of monoclonal antibodies (MAbs) E48 and U36 directed against HNSCC-associated antigens, and the molecular characterization of these antigens. Novel strategies for the detection of minimal residual disease are outlined and comprise the use of immunocytochemistry in combination with automated image analysis, and the use of an E48-specific reverse transcriptase-polymerase chain reaction (RT-PCR) method. These methods have potential for the detection of single HNSCC cells in lymph nodes, bone marrow and peripheral blood, and may contribute to the better staging of head and neck cancer in the near future. Besides this, preclinical and clinical data on HNSCC targeting with radiolabelled MAbs E48 and U36 are summarized, illustrating the perspectives of systemic adjuvant radioimmunotherapy with these MAbs.

Antigens, Neoplasm