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Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

At least 181 records · Page 10Linked to original sources

Squamous cell carcinoma of the nasal vestibule.

We reviewed 30 patients with squamous cell carcinoma of the nasal vestibule to present our experience of their management and to evaluate the prognostic factors that may influence their outcome. For T1 lesions radiotherapy remains the treatment of choice, because of the superior cosmetic result. Fifteen (68 per cent) out of 22 patients with T2 lesions were treated with primary radiotherapy. Surgery however, was eventually required in 16 (72 per cent) out of 22 patients, either as a primary treatment (seven patients) or as salvage surgery (nine patients). For the larger T3 lesions the treatment of choice is surgery followed by post-operative radiotherapy where appropriate. Regional nodal metastases at the time of presentation were a significant indicator of local and regional recurrence and of prognosis. The cause specific five-year survival for patients with an uninvolved neck (22 patients) was 100 per cent compared with 38 per cent for patients with nodal metastases at presentation (eight patients). Elective treatment for uninvolved regional nodes is not considered necessary.

Adult↗

Radioimmunotherapy of human head and neck squamous cell carcinoma xenografts with 131I-labelled monoclonal antibody E48 IgG.

Monoclonal antibody (MAb) E48 reacts with a 22 kD antigen exclusively expressed in squamous and transitional epithelia and their neoplastic counterparts. Radiolabelled with 99mTc, MAb E48 is capable of targeting metastatic and recurrent disease in patients with head and neck cancer. In this study, the capacity of 131I-labelled MAb E48 to eradicate xenografts of human squamous cell carcinoma of the head and neck (HNSCC) in nude mice was examined. Experimental groups received a single i.v. bolus injection of 400 microCi MAb E48 IgG (number of mice (n = 6, number of tumours (t) = 9) or 800 microCi MAb E48 IgG (n) = 5,t = 7), whereas control groups received either diluent (n = 3,t = 5), unlabelled MAb E48 IgG (n = 4,t = 5) or 800 microCi 131I-labelled isotype-matched control MAb (n = 6,t = 9). A 4.1-fold increase in the median tumour volume doubling time and regression of two out of ten tumours (20%) was observed in mice treated with 400 microCi. In mice treated with 800 microCi. In mice treated with 800 microCi, two out of seven tumours (29%) showed complete remission without regrowth during follow-up (greater than 3 months). Median tumour volume doubling time in the remaining five tumours was increased 7.8-fold. No antitumour effects were observed in mice injected with diluent, unlabelled MAb E48 or 131I-labelled control MAb. In the same xenograft model, chemotherapy with doxorubicin, 5-fluorouracil, cisplatin, bleomycin, methotrexate or 2',2'-difluorodeoxycytidine yielded a less profound effect on tumour volume doubling time. Increases in tumour volume doubling time with these chemotherapeutic agents were 4, 2.2, 2.1, 1.7, 0, and 2.6 respectively. Moreover, no cures were observed with any of these chemotherapeutic agents. From the tissue distribution of 800 microCi MAb E48, the absorbed cumulative radiation doses of tumour and various organs were calculated using the trapezoid integration method for the area under the curve. To tumour xenografts, 12,170 cGy was delivered, blood received 2,984 cGy, whereas in every other tissue the accumulated dose was less than 6% of the dose delivered to tumour. These data, describing the first radiolabelled MAb with therapeutic efficacy against HNSCC, suggest radioimmunotherapy with MAb E48 to be a potential therapeutic modality for the treatment of head and neck cancer.

Animals↗

Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA.

This study was undertaken to determine whether human papillomavirus (HPV) E6/E7 gene transcription in tonsillar carcinomas is correlated with viral DNA integration. Therefore, tonsillar carcinomas containing HPV-16 (n = 2) and HPV-33 (n = 2) DNA were analysed for the viral physical state and transcription of the E6/E7 region. Southern blot analysis, DNA polymerase chain reaction (PCR) and, eventually, two-dimensional gel electrophoresis revealed indications for the presence of only episomal DNA in the HPV-16-containing biopsies and only integrated DNA in one HPV-33-containing biopsy. The second HPV-33-containing carcinoma, from which one biopsy and two resected tumour specimens were analysed, showed a rather complex physical state profile. The biopsy of this tumour contained only episomal DNA, one resected tumour part contained only integrated DNA and the remaining tumour part contained both integrated and episomal HPV-33 DNA. Independent of the viral physical state, all biopsies and resected tumour parts tested showed the presence of E6/E7 transcripts as determined by RNA PCR. The results indicate that E6/E7 transcripts in tonsillar carcinomas can originate from integrated as well as episomal HPV DNA.

Base Sequence↗

T3 laryngeal cancer: a retrospective study of the Dutch Head and Neck Oncology Cooperative Group: study design and general results.

511 Patients with T3 N0-3 M0 squamous cell carcinoma of the larynx, treated in the Netherlands from 1975 until 1984, were retrospectively analysed. Four different treatment policies were followed: primary surgery, planned combination of radiotherapy and surgery, primary radical radiotherapy, and selective radiotherapy. General results are presented. Local control rate was 72%. Regional control rate was 90% for clinically N0 patients and 78% for clinically N+ patients. Salvage therapy was overall successful in 38%. Surgical salvage for local radiation failures (with regional relapse) was successful in 69%, and for regional failures (without local relapse) in 46%. Ultimate locoregional control was 78% and, due to 8% distant metastases, 5-year actuarial corrected survival was 70%. Prognosis did not improve over the years. Corrected survival was independently correlated with tumour extension, involvement of neck nodes and treatment strategy. Corrected survival was similar for primary radiotherapy and primary surgery, but significantly better for planned combined therapy. Multiple primary tumours occurred significantly more often in male (19.5%) than in female patients (7.3%) (P = 0.05), the bronchus being most commonly affected. Cumulative actuarial risk for metachronous tumour was 15% after 5 years and 30% after 10 years so prevention and early detection of these second tumours may play the most important role in improving overall survival rates in the future.

Adult↗

Possible premalignant character of oral lichen planus. The Amsterdam experience.

In the present paper the 21-yr experience of the Department of Oral and Maxillofacial Surgery and Oral Pathology, and the Department of Otorhinolaryngology of the Free University Hospital, Amsterdam, is reported with regard to the possible premalignant character of oral lichen planus. The study consists of two parts: 1) the follow-up of 113 patients with histopathologically proven oral lichen planus, and 2) a search for lichen planus in 727 patients who have been admitted for oral cancer. Three patients with histopathologically proven lichen planus developed a squamous cell carcinoma in an average follow-up period of 7 yr. In the 727 patients with oral cancer, two additional patients with the simultaneous occurrence of oral lichen planus were observed. Our experience gives some but not very strong support to the hypothesis that oral lichen planus is a premalignant condition.

Adult↗

Histological reclassification of 101 intraoral salivary gland tumours (new WHO classification).

The epithelial salivary gland tumours have for many years been categorised according to the 1972 World Health Organisation (WHO) classification. In 1990 a proposed revision of this classification was elaborated. In this study 101 intraoral salivary gland tumours were reclassified accordingly. In 29 of the cases the original histological diagnosis was changed, which in most cases, occurred in the benign or malignant tumour groups. In seven cases the diagnosis was changed from benign to malignant or vice versa. The results of this study show that the histological classification of intraoral salivary gland tumours remains difficult, even when applying the new WHO classification.

Adolescent↗

Metastases of carcinoma of the larynx.

The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer, and the management of metastatic disease plays an important role in the treatment of carcinoma of the larynx. Clinical assessment of the neck is not very accurate, and the role of newer imaging techniques such as CT, MRI and Ultrasound guided Fine Needle Aspiration Cytology is being assessed, in order to improve upon the results of clinical palpation alone. The site of the primary tumour within the larynx is an important factor in affecting the frequency and the pattern of lymph node metastases to the neck. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of lymph node metastases of carcinoma of the larynx are discussed with reference to the various sites of the primary tumour.

Diagnostic Imaging↗

Preclinical in vivo activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human head and neck cancer.

2',2'-Difluorodeoxycytidine (dFdCyd, Gemcitabine) is a new deoxycytidine analogue with striking preclinical antitumor activity in solid tumors from murine and human origin. In this study, dFdCyd was tested for its antitumor effect in human tumor xenografts derived from squamous cell carcinoma of the head and neck (SCCHN). NMRI nude mice bearing s.c. growing tumors with a volume of 50 to 150 mm3 were given i.p. injections of a maximum tolerated dose of 120 mg/kg dFdCyd, every 3 days for four injections. A significant antitumor effect was observed in all five tested SCCHN tumor lines; in four of these lines the median tumor volume doubling time increased more than a 3-fold upon dFdCyd treatment. In two lines dFdCyd was curative (no tumor regrowth 90 days after treatment) in one of six and two of eight xenografts, respectively. Schedule dependency was investigated in three SCCHN lines, showing, in the two most sensitive lines, that treatment with a 3-day interval was superior to the schedules with daily or weekly injections. At equitoxic doses, dFdCyd was more active in this model than the drugs that are clinically used in SCCHN, i.e., cisplatin, methotrexate, 5-fluorouracil, and cyclophosphamide. dFdCyd is a good candidate for clinical trials with SCCHN patients.

Animals↗

Magnetic resonance imaging vs palpation of cervical lymph node metastasis.

In a series of 100 patients with head and neck carcinoma, the preoperative histopathologic findings of palpation and magnetic resonance imaging were compared with regard to both laterality and lymph node level (I through V). The overall error for palpation in detecting affected sides was 32%. Gadolinium-enhanced magnetic resonance images reliably upgraded 60% of the clinically negative necks, the overall error of magnetic resonance imaging being 16%. However, for both modalities, the sensitivity per level was too low to allow for selective neck dissections in case of only one positive level. These findings show that apart from primary tumor grading, magnetic resonance imaging can improve the preoperative grading of cervical lymph nodes. In selected cases, this may change the treatment plan to a "wait-and-see" policy or a more conservative type of neck dissection.

Aged↗

Discontinuous vs in-continuity neck dissection in carcinoma of the oral cavity.

We compared the results of transoral excision of the primary tumor with discontinuous neck dissection with the results of in-continuity dissection of primary tumor and neck nodes in anteriorly localized squamous cell carcinoma of the oral cavity. We analyzed 27 patients who underwent 28 discontinuous dissections and 34 patients who underwent 40 in-continuity dissections for T2 anterior tongue or floor-of-mouth carcinoma. The overall ipsilateral neck recurrence rate was 11%. The discontinuous dissection group did significantly worse than the in-continuity dissection group, with a neck recurrence rate of 19%. Consequently, the actuarial 5-year survival of patients who underwent a discontinuous dissection was substantially decreased (63%) compared with patients who were treated by an in-continuity dissection (80%). Discontinuous neck dissection, thus, is not to be recommended in oral cancer.

Adult↗

Detection of squamous cell carcinoma xenografts in nude mice by radiolabeled monoclonal antibody E48.

We recently produced the monoclonal antibody E48 as a specific reagent for squamous cell carcinomas. In our ongoing investigations to use E48 for clinical tumor detection and therapy, fundamental aspects of the antigen have to be elucidated and practical applications of the antibody have to be tested in a preclinical model. Immunoelectron-microscopic studies localized the E48 antigen along the cell surface and in between desmosomes, suggesting that the antigen serves as an adhesion molecule. To evaluate the usefulness of E48 for radioimmunodetection of neck node metastases, nodes from 20 neck dissection specimens were tested. A strong reactivity was observed. Furthermore, F(ab')2 fragments of E48 were compared with the complete IgG E48 for selective tumor detection in an animal model. It was demonstrated that E48 F(ab')2 fragments localize faster and reach higher tumor-nontumor ratios than the whole molecule.

Animals↗

Sinonasal non-Hodgkin's lymphomas and Wegener's granulomatosis: a clinicopathological study.

Reports of sinonasal non-Hodgkin's lymphomas, analysed with monoclonal antibodies, are scarce, and differentiation of these lymphomas from Wegener's granulomatosis can be difficult. In this study, we investigated histopathologically and immunohistologically 20 cases of non-Hodgkin's lymphoma, primary in the sinonasal region, and sinonasal biopsies from 11 patients with Wegener's granulomatosis. All T-cell lymphomas (n = 7) and plasmacytomas (n = 4) were stage I at clinical presentation, while all B-cell lymphomas (n = 9) presented at higher stages. T-cell lymphomas tended to be more frequent in the nasal cavity and paranasal sinuses; B-cell lymphomas more often presented in the nasopharynx. Remarkably, 1 B-cell lymphoma expressed MT1, and 1 T-cell lymphoma expressed L26 (CD 20). The follow-up of 2 patients with a clinical diagnosis of Wegener's granulomatosis was suggestive of non-Hodgkin's lymphoma. Retrospective immunohistochemical analysis revealed that the original histological diagnosis of non-specific inflammation had to be changed to T-cell lymphoma, pleomorphic small cell type. We conclude that a biopsy from the sinonasal region with a dense inflammatory infiltrate, consisting predominantly of T-lymphocytes, renders a diagnosis of Wegener's granulomatosis unlikely and is at least suspicious of T-cell lymphoma. Immunohistochemical analysis is warranted for this type of biopsy.

Adult↗

Lymph node staging in patients with clinically negative neck examinations by ultrasound and ultrasound-guided aspiration cytology.

To assess the usefulness of ultrasound and ultrasound-guided fine-needle aspiration cytology in detecting occult cervical lymph node metastases, 107 patients with squamous cell carcinoma of the head and neck, who underwent 132 elective neck dissections, had preoperative ultrasound examination. During the assessment of the last 54 patients, who underwent 70 elective neck dissections, ultrasound-guided aspiration cytology was available. Although ultrasound was able to detect lymph node metastases in the majority of patients, the accuracy of this technique never exceeded 70% (93 of 132 procedures). With ultrasound-guided aspiration cytology, accuracy was 89% (62 of 70 procedures). This latter technique seems to be the modality of choice for the assessment of the clinically negative neck. Its use obviates the need for elective neck dissection, done because of the high risk of occult metastasis.

Biopsy, Needle↗

Evidence for a role of the monoclonal antibody E48 defined antigen in cell-cell adhesion in squamous epithelia and head and neck squamous cell carcinoma.

Monoclonal antibody (MAb) E48 recognizes a 20- to 22-kDa antigen expressed by human squamous and transitional epithelia and their neoplastic counterparts. Histochemical examination of these tissues revealed distinct surface labeling with MAb E48. To investigate the subcellular localization of the E48 antigen we have performed electron microscopical analysis. In cells of normal oral mucosa, the E48 antigen was expressed on the plasmalemma, particularly associated with desmosomes, suggesting involvement of the E48 antigen in intercellular adhesion. Furthermore, the level of expression of the E48 antigen appeared to be influenced by the cellular organization. In squamous cell carcinoma (SCC) cell lines grown in vitro as subconfluent monolayer cultures, the E48 antigen expression was low. However, E48 antigen expression increased when SCC cells were grown to confluency. E48 antigen expression was similarly high when SCC cell lines were cultured under conditions promoting three-dimensional growth either as colonies within floating collagen gels or as xenograft in tumor-bearing nude mice. Further evidence for the involvement of the E48 antigen in cell-cell adhesion was found when SCC cells were grown within collagen gels in the presence of MAb E48: no spherical colonies were formed, but cells grew out to colonies composed of single cells. Moreover, in this culture system the percentage of SCC cells growing out to colonies was decreased by the presence of MAb E48. These findings indicate that the E48 antigen is involved in the structural organization of squamous tissue and might have a role in intercellular adhesion.

Antibodies, Monoclonal↗

Superior localisation and imaging of radiolabelled monoclonal antibody E48 F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody E48 IgG.

Monoclonal antibody (MAb) E48 and its F(ab')2 fragment, radiolabelled with 131I, were tested for tumour localisation and imaging in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma (HNX-HN) or from a vulva carcinoma (VX-A431). MAb IgG or F(ab')2 fragments were injected in parallel and at day 1, 2, 3 and 6 or 7, mice were either scanned with a gamma camera or dissected for determination of isotope biodistribution. In HNX-HN bearing mice, E48 IgG as well as F(ab')2 showed highly specific localisation in tumour tissue. The mean tumour uptake (n = 4) expressed as the percentage of the injected dose per gram of tumour tissue (percentage ID/g) of IgG was 11.9% at day 1 and increased to 14.6% at day 6 whereas percentage ID/g of F(ab')2 was 7.2% at day 1 and decreased during subsequent days. Tumour to blood ratios (T/B) at day 1 were 1.2 for IgG and 13.6 for F(ab')2 and reached a maximum at day 6 with values of 6.4 and 54.2 respectively. In VX-A431 bearing mice, only E48 F(ab')2 showed preferential localisation in tumour tissue. At day 1, Percentage ID/g of IgG was 3.7 and T/B was 0.3, while percentage ID/g of F(ab')2 was 2.4 and T/B was 3.2. Percentage ID/g decreased after day 1 while T/B increased. In these experiments no preferential localisation of either isotype matched 125I-labelled control IgG or F(ab')2 was observed. In F(ab')2 injected HNX-HN bearing mice as well as VX-A431 bearing mice, tumours could be visualised at day 1 and 2 without any appreciable background activity. With MAb IgG this was also possible in HNX-HN bearing mice (but not in VX-A431 bearing mice) but only at day 3 and 6. These findings suggest that the superior tumour to non-tumour ratios render the E48 F(ab')2 fragment more qualified for specific targeting of radioisotopes to tumour xenografts in this experimental setting.

Animals↗

Carcinoembryonic antigen and head and neck cancer.

Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated (greater than or equal to 2.5 ng/ml). Only 13% of the patients had clearly elevated CEA levels (greater than 5 ng/ml). CEA levels were significantly higher in patients with advanced, e.g. stage IV, disease but a correlation between serum CEA concentration and prognosis was not found. Patients who smoked had significantly higher serum CEA levels than non-smoking patients. In the serial determinations slight CEA elevations could be found in only 50% of patients with tumour recurrence. Combined with the data from the literature we conclude that serum CEA determination is not useful in predicting the outcome in patients with a head and neck squamous carcinoma.

Adult↗