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Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

At least 127 records · Page 7Linked to original sources

The value of magnetic resonance imaging in the differential diagnosis of parapharyngeal space tumours.

Between 1987 and 1993 14 patients with a parapharyngeal space tumour were imaged by magnetic resonance imaging (MRI). The vagal body tumours, presenting in the poststyloid compartment, all showed flow voids with anterior and medial displacement of the internal carotid artery. None of the salivary gland tumours, all presenting in the prestyloid compartment with posterior displacement of the internal carotid artery, showed flow voids. MRI is superior compared with other modalities in evaluating the differential diagnosis, especially regarding vascular vs non-vascular tumours. It should encompass T1 SE images to assess the presence or absence of flow voids. In vascular tumours angiography must be used to assess feeding vessels, multiplicity, and sides involved. T1 GE images are useful as they allow superior identification of the internal carotid artery and its relation with the tumour accordingly. In addition to T1 SE images, T2 SE images may help in the evaluation of the differential diagnosis. In all non-vascular tumours aspiration cytology is required to differentiate between benign and malignant disease.

Adenocarcinoma↗

Circulating fragments of cytokeratin 19 in patients with head and neck squamous cell carcinoma.

In head and neck squamous cell carcinoma a reliable serum marker of carcinogenesis should be of predictive value for the development of recurrent disease or a second primary tumour. At the moment, such a tumour marker is not available. Recently, elevated levels of cytokeratin 19-fragments (Cyfra 21-1) have been detected in the serum of patients with lung cancer, in particular with squamous cell carcinoma. Cytokeratin 19 is an intermediate cell filament protein expressed in simple epithelia and their malignant counterparts. Therefore, in this prospective study, a standardized sandwich enzyme-linked immunosorbent assay for soluble cytokeratin 19 fragments was tested in the serum of 20 patients with a previously untreated head and neck squamous cell carcinoma. The results were compared with that of 20 control individuals. Our results showed significantly higher Cyfra 21-1 concentrations in the serum of patients with cancer (10.21 +/- 3.03 ng/ml) than the controls (7.2 +/- 2.63 ng/ml). After radical treatment the marker levels dropped significantly to 1.65 +/- 1.07 ng/ml. Cyfra 21-1 appears to be of value as a circulating tumour marker for head and neck squamous cell carcinoma especially in monitoring disease control.

Adult↗

Predictive value of MR imaging-dependent and non-MR imaging-dependent parameters for recurrence of laryngeal cancer after radiation therapy.

PURPOSE: To determine the predictive value of several clinical and radiologic parameters for recurrence of laryngeal cancer. MATERIALS AND METHODS: Eighty previously untreated patients underwent magnetic resonance (MR) imaging before radiation therapy with curative intent. Tumor volume was calculated from T1-weighted MR images. Cartilage was considered invaded by pathologic tissue if it had intermediate signal intensity on T1-weighted spin-echo (SE) MR images and high signal intensity on T2-weighted SE MR images. The minimum follow-up was 2 years. RESULTS: Parameters such as age, sex, histopathologic findings, and invasion of the vocal muscle or pre-epiglottic space were not significantly correlated with tumor recurrence. Logistic regression analysis showed three relevant contributors: cord mobility, as judged clinically, and tumor volume and, more significantly, cartilage invasion, as seen at MR imaging. CONCLUSION: For untreated laryngeal cancer, MR imaging findings of tumor volume and cartilage invasion allow better patient selection for either radiation therapy or surgery. MR imaging is mandatory for T staging of laryngeal cancer.

Adult↗

Second primary head and neck squamous cell carcinoma predicted by the glutathione S-transferase expression in healthy tissue in the direct vicinity of the first tumor.

BACKGROUND: Glutathione S-transferases (GST) are known to play a role in the detoxification of carcinogens. Individual isoenzymes of the alpha-, mu-, and pi-class vary in substrate specificities, tissue distribution, and activities among individuals. GST-pi expression has been shown to be increased in preneoplastic and neoplastic lesions. GST-mu is known to play a role in detoxification of epoxides released from cigarette smoke, and individuals with low GST-mu activity have a relatively high risk to develop smoking-related lung and laryngeal cancer. The occurrence of a second primary tumor (SPT) in the whole respiratory and upper aerodigestive tract is an important factor for mortality in head and neck squamous cell carcinoma (HNSCC), and, at present, there are no markers that are available to predict which patient has increased chances of developing an SPT. Risk-assessment by use of biomarkers, particularly the ones that can be obtained with noninvasive techniques, are of great value in predicting prognosis and hence possibly more aggressive treatment and follow-up in selected patient groups. EXPERIMENTAL DESIGN: In a nested case control study, 20 patients who had previous history of oral cancer were used; 10 of the 20 had developed an SPT, and the other 10 patients were minimally 7 years free of disease. The expression of GST-pi, GST-mu, and GST-alpha was immunohistochemically analyzed using apparently normal oral mucosa, free of tumor or dysplasia, obtained from the resection edges around the primary tumor. In another experiment, the three GST isoenzymes were immunohistochemically analyzed using exfoliated cells, obtained noninvasively from several sites of the upper aerodigestive tract of the apparently normal-looking mucosa of HNSCC patients (n = 25) and of control individuals (n = 10). RESULTS: The expression of all GST was significantly higher (p < 0.001) in the suprabasal and superficial layers of the mucosa at risk. Also, in cell scrapes of clinically healthy mucosa of HNSCC patients, we observed a significantly higher expression (p < 0.001) of GST-pi and GST-mu compared with their matched controls. For GST-alpha, we observed a more heterogenous expression pattern in these exfoliated cells. CONCLUSIONS: Expression of GST-pi, -mu, and -alpha in normal tissue in the direct vicinity of the first tumor seems to have predictive value for the development of an SPT.

Adult↗

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↗

[Satisfactory 5-year survival in 29 patients following surgery of a small metastasized tongue carcinoma (T1N0M0)].

OBJECTIVE: To determine the five-year survival rate of patients with a small (< 2 cm) squamous cell carcinoma of the anterior two-thirds of the tongue that had not shown evident cervical lymph node metastases at presentation. DESIGN: Follow-up investigation. SETTING: Free University Hospital, Amsterdam. METHOD: In the period January 1st, 1970 to December 31, 1986, 36 patients were registered with a T1N0M0 squamous cell carcinoma of the anterior two-thirds of the tongue. Seven patients were excluded from follow-up study for various reasons (multiple carcinoma (4), histological diagnosis doubtful (2), lost to follow-up (1)). All remaining 29 patients were primarily treated by surgical excision with a margin of healthy tissue of approximately 1 cm. RESULTS: In five patients (17%) a local recurrence was observed, in 7 (24%) one or more cervical lymph node metastases developed. Four patients withdrew from follow-up, three died from their tongue cancer, all within two years. Of the 22 patients who did not withdraw from follow-up and who did not die from other causes 19 (86%) were alive and well after five years. CONCLUSION: Patients with a small squamous cell carcinoma of the anterior two-thirds of the tongue in whom initially no cervical lymph node metastases were palpable and who have primarily been treated by surgery, stand a good chance of cure, in spite of the development of regional lymph node metastases in almost 25% of them.

Adult↗

Increased mutagen sensitivity in head-and-neck squamous-cell carcinoma patients, particularly those with multiple primary tumors.

Mutagen sensitivity is a constitutional factor which may be used to identify head-and-neck squamous-cell carcinoma (HNSCC) patients at high risk for the development of multiple primary tumors (MPT). In this retrospective study, mutagen sensitivity was measured in HNSCC patients with a single primary tumor (SPT), HNSCC patients who have already developed MPT and control subjects with no tumor history. In vitro, lymphocytes were challenged with bleomycin and chromosomal damage was quantified by scoring chromatid breaks of 100 cells. A significant difference in the mean number of breaks per cell (b/c) was found between SPT patients and controls. Patients with MPT showed a significantly higher mean b/c value than SPT patients. This increase in mutagen sensitivity in HNSCC patients was not related to well-known cancer risk factors such as age, or life-style factors such as smoking and alcohol drinking habits. In addition, tumor site but not tumor stage was found to be related to mutagen sensitivity. On the basis of our findings, we propose that mutagen sensitivity is not an independent risk factor but a constitutional factor which reflects the way in which genotoxic compounds are dealt with and is thereby directly related to cancer risk.

Aged↗

Primary malignant melanoma of the oral cavity: a review of eight cases.

A review of oral malignant melanoma and data of eight patients are presented. The dismal prognosis of the condition is probably mainly due to its long, 'silent' course. In one-third of cases melanosis precedes the tumour--it is this condition that should alert clinicians. Therefore, pigmented oral lesions should be viewed with suspicion and biopsy is mandatory when the clinical diagnosis is uncertain. Early detection is essential to successful treatment. In spite of aggressive treatment modalities, survival in patients with advanced stage disease remains poor.

Adult↗

Risk of multiple primary tumors following oral squamous-cell carcinoma.

The follow-up of 727 patients with squamous-cell carcinoma (SCC) of the lip and oral cavity has been used for the risk analysis of multiple primary tumors (MPTs) following SCC of the lip and oral cavity. Age-, gender- and site-specific cancer-incidence rates from the general population have been applied to the appropriate persons-years of follow-up of patients with SCC of the lip and oral cavity. The study indicates that patients with a primary SCC of the lip and oral cavity have, compared with the general population, a significantly elevated risk of developing an additional cancer of the oral cavity and/or pharynx, the risk being 74.7-fold for males and 190.4-fold for females. Furthermore, a 24.6 and 45.3 times higher risk of an additional esophageal tumor was found in males and females respectively. The risk of cancer of the lung and pharynx was less elevated compared with the risk of cancer of the upper digestive tract. No elevated risks were established in organs outside the respiratory and upper digestive tract.

Aged↗

Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor.

BACKGROUND: Biologic aggressiveness of head and neck carcinoma is reflected in its capability to metastasize to regional lymph nodes and its propensity to recur after treatment. METHODS: The authors report on 244 patients treated at the Department of Otolaryngology-Head and Neck Surgery of the Free University Hospital, Amsterdam, The Netherlands, with excision of primary tumor with incontinuity neck dissection with or without postoperative radiation therapy between January 1973 and July 1986. All patients had surgical margins free of tumor. RESULTS: The overall recurrence rate was 12.3%. Stages T3-4 and the presence of more than three positive nodes on histopathologic examination were associated with a 16.2% and 26.2% incidence in recurrence at the primary site, respectively. No prognostic influence arose from primary tumor localization, three or fewer positive nodes, extranodal spread, and postoperative radiation therapy. CONCLUSIONS: Patients with T3-4 disease and those with more than three positive lymph nodes may benefit from novel adjuvant treatment modalities.

Adult↗

Complete ablation of small squamous cell carcinoma xenografts with 186Re-labeled monoclonal antibody E48.

In previous studies we have shown that in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts, radioimmunotherapy (RIT) with 186Re-labeled MAb E48 resulted in complete regressions in one-third of the tumors (followup > 150 d). MAb E48 was labeled with 186Re following a novel labeling procedure developed at our institute. The injected dose was 600 microCi, which was the maximum tolerated dose (MTD; < 15% wt loss) in these studies. The mean size of the tumors was 140 +/- 60 mm3. To investigate whether the therapeutic efficacy of RIT in our xenograft model would be improved when treating smaller xenografts, mice bearing 2 HNSCC xenografts with a vol of 75 +/- 17 mm3 (number of mice, n = 6; number of tumors, t = 12) were treated with 600 microCi of 186Re-labeled MAb E48 IgG. All tumors completely regressed and did not regrow during followup (> 150 d). In all mice, weight loss did not exceed 10%. To obtain biodistribution data, mice bearing two xenografts with a vol of 58 +/- 31 mm3 were injected with 100 microCi of 186Re-labeled MAb E48 IgG. The maximum uptake in blood was 26.4% injected dose/g (%ID.g-1) at 2 h pi and was 53.1%ID.g-1 in the tumor at d 7 pi. In normal tissues, no nonspecific accumulation was observed. Based on these biodistribution data, the absorbed cumulative radiation dose was calculated. The accumulated dose in blood and tumor was 2004 cGy and 8580 cGy, respectively. In other tissues, the dose was less than 8.1% of the dose delivered to tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Second respiratory and upper digestive tract cancer following oral squamous cell carcinoma.

727 patients with squamous cell carcinoma (SCC) of the lip and oral cavity have been followed for the occurrence of second primary tumours (SPTs) in the respiratory and upper digestive tract (RUDT). 74 patients (10%) developed at least one SPT in the RUDT. The incidence of SPTs was expressed per 1000 person-years of follow-up. In our study about 28 SPTs per 1000 person-years of follow-up were seen in the RUDT. Patients were at risk for a second primary tumour, at a steady rate of approximately 2.8% per year during at least 10 years. Furthermore, patients with an index tumour in the lower part of the mouth (floor of mouth, retromolar area and lower alveolar process), which is more related to tobacco and/or alcohol, seem to be more at risk for SPTs than patients with an index tumour in the other (sub)sites of the mouth.

Aged↗

Radical surgical treatment in craniofacial osteosarcoma gives excellent survival. A retrospective cohort study of 14 patients.

14 patients with an osteosarcoma of the craniofacial bones were evaluated retrospectively. 10 patients were males and 4 were females, ages varied from 10 to 74 years with a mean of 37 years. Ten tumours were located in the maxilla and four in the mandible. All patients underwent surgical resection of the tumour. One patient was irradiated postoperatively with 67.5 Gy and another patient received adjuvant chemotherapy with melphelan. Follow-up ranged from 6 months to 10 years with a mean of 4 years 2 months. Of 14 patients, 5 have died of local disease of whom 1 also had distant metastasis. Disease-free survival was 82.5% after 2 years and 68.8% after 5 years. Overall survival was 79.1% after 5 years. Univariate statistical analysis was carried out, revealing age < 35 years (P = 0.033) and radical surgery (P = 0.007) as statistically significant factors in disease-free survival. It is concluded that radical surgery in young patients with a craniofacial osteosarcoma gives long-term disease-free survival.

Adolescent↗

The feasibility of radioimmunotherapy of head and neck cancer.

Since the introduction of the hybridoma technology by Kohler and Milstein (Nature 1975, 256, 495-497), tremendous effort has been put in the realisation of Ehrlich's concept of the magic bullet, which was proposed as early as the beginning of the century. The first clinical studies for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) with radiolabelled antibodies were undertaken in the early 1980s. Since then, RIS has been performed on thousands of patients with various types of malignancies, like colon carcinoma, lung carcinoma, breast carcinoma, neuroblastoma, T-cell lymphoma and ovarian carcinoma. In addition, a substantial number of therapy trials with radiolabelled antibodies have been performed. The developments for head and neck squamous cell carcinoma (HNSCC) have only recently been able to catch up with these events to some extent. One of the main reasons for this slow progress has been the lack of monoclonal antibodies (Mab) with specificity for HNSCC. Although there are as yet no real tumour specific antigens known for HNSCC, which also holds true for the majority of malignancies arising from other tissues, we now have the availability of a number of Mab with high specificity for HNSCC and with a very restricted reaction pattern with normal tissues. Labelled with 131I, these Mab have been shown to be highly capable to localise in HNSCC xenografts in nude mice. Based on these promising data, patient studies with one of these Mab, designated Mab E48, labelled with 99mTc, were started to evaluate the feasibility of RIS in patients with head and neck cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗