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PubMed1977

Persistent carcinoma of the oropharynx and oral cavity re-treated by after-loading interstitial 192Ir implant.

After-loading implantation techniques apparently offer an effective alternative in the management of persistent (or recurrent) oropharynx and oral cavity carcinoma postirradiation. A total of 29 patients with such lesions was treated from February 1974, to July 1975, in the LAC/USC Radiation Medicine Section, using after-loading 192Ir implantation techniques. These patients all had extensive persistent cancer after "full tolerance" irradiation (with or without previous surgery) and were referred for palliation or for possible salvage. Additional doses administered ranged from 5000 to 7000 rads in three to five days. Eighteen of the 29 patients (63%) have had complete local control for 18 to 36 months. These patients have maintained a relatively satisfactory palliative status. Ten of the 29 are dead. Follow-up periods are short, but early indications are that problem patients with persistent cancer after "full tolerance irradiation" can be salvaged, or at least satisfactorily palliated, with after-loading interstitial implant techniques. Clinical details, sites of involvement, implantation techniques, dosimetry methodology, reactions and complications will be described.

Adult↗
PubMed1992

Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

Of 142 patients irradiated for American Joint Committee on Cancer Stage III or IV head and neck carcinoma, 100 patients were eligible for analysis with a minimum follow-up of 12 months. In one group, 50 patients were treated with conventional once-a-day (QD) fractionation to doses in excess of 6600 cGy. The other 50 patients were treated prospectively with accelerated superfractionated radiation therapy using a concomitant boost twice-a-day schedule (BID). Patients received conventional fractionation (180 cGy/fraction) combined with a boost field of 160 cGy/fraction BID after a 4-hour to 6-hour interval 3 days per week during part of their treatment course. After 3 years, locoregional tumor control was 62% in the BID group versus 33% in the QD group (P = 0.003). Disease-free survival was 60% and 30%, respectively, for the BID and QD groups (P = 0.002), and adjusted survival was 66% and 38%, respectively, for the BID and QD groups (P = 0.03). Overall survival approached statistical significance in favor of the BID group (P = 0.06). Complete tumor responses were observed in 63% of patients treated in the BID group 1 to 3 months after completion of radiation therapy. Of these, 84% remain free of local recurrence. Of the 19 patients with persistent disease 1 to 3 months after treatment, 47% remain locally controlled. Superfractionated accelerated radiation therapy produced superior local control and disease-free and adjusted survival rates relative to a group of patients treated QD.

Carcinoma, Squamous Cell↗
PubMed1992

Simultaneous assay of adenosine deaminase and purine nucleoside phosphorylase activity as possible biochemical means to detect non-Hodgkin lymphomas of the oral cavity.

BACKGROUND AND METHODS: This study proposes the usefulness of simultaneous assay of adenosine deaminase (enzyme code [EC] 3.5.4.4; ADA) and purine nucleoside phosphorylase (EC 2.4.2.1; PNP) activities in a biopsy specimen as a biochemical test adjunctive to the histologic diagnosis of oral non-Hodgkin lymphomas (NHL). RESULTS: NHL tissues showed an ADA activity of more than 1428 nmol/h/mg of protein, and more than 3451 nmol/h/mg of protein was the sum of ADA and PNP activity. In contrast to this finding, all the 106 lesional tissues affected by various carcinomas, various benign tumors, various cysts, ameloblastomas, osteosarcomas, gingival hyperplasia, and inflammation showed an ADA activity of less than 1000 nmol/h/mg of protein, except for 2. The sum of ADA and PNP activity was less than 2249 nmol/h/mg of protein in these diseases, except for squamous carcinoma. Different control tissues of the oral cavity showed less than 766 nmol/h/mg of protein in ADA activity, and the highest sum of ADA and PNP activity in these was only 1384 nmol/h/mg of protein. CONCLUSIONS: These findings suggest that a strong suspicion of oral NHL is justified when the sum of ADA and PNP activity in a biopsy specimen exceeds 3000 nmol/h/mg of protein and ADA activity is greater than 1000 nmol/h/mg of protein.

Adenosine Deaminase↗
PubMed2000

Suprabasal expression of Ki-67 antigen as a marker for the presence and severity of oral epithelial dysplasia.

BACKGROUND: Suprabasal expression of Ki-67 is assessed as a marker for oral dysplasia. The study involved non-neoplastic epithelium adjacent to 74 oral squamous cell carcinomas. METHODS: An immunohistochemical technique was carried out (peroxidase-antiperoxidase) with the monoclonal antibody MIB-1. Epithelial expression of Ki-67 was classified as being absent, basal, and suprabasal. The epithelium was normal in 19 cases, hyperplastic in 38 cases, and dysplastic in 37 cases. The dysplasia was slight in 20 cases, moderate in 12 cases, and severe in 5 cases. RESULTS: The results of the expression of Ki-67 were in normal epithelium, basal expression 9 cases, absent 10 cases; in hyperplastic epithelium, basal expression 18 cases, absent 20 cases; in dysplastic epithelium, basal and suprabasal expression (always jointly) 27 cases, absent 10 cases; all the severe and moderate dysplasia cases expressed suprabasal Ki-67. A significant association was observed between the presence (p <.0001) and severity (p <.007) of the dysplasia and the suprabasal expression of Ki-67.

Adult↗
PubMed2006

Discrimination of normal, inflammatory, premalignant, and malignant oral tissue: a Raman spectroscopy study.

Optical spectroscopy methods are fast emerging as potential alternatives for early diagnosis of cancer. A Raman spectroscopy method for discrimination of normal and malignant oral tissues has been developed by us earlier. It is necessary to evaluate and establish the validity of the approach before it can be routinely used. In the present study, our Raman spectroscopy investigations are extended further to evaluate the efficacy of the technique to discriminate between normal, inflammatory, premalignant, and malignant conditions in oral tissue. Spectral profiles of normal, malignant, premalignant, and inflammatory conditions show pronounced differences between one another. Spectra of normal tissues can be attributed mainly to lipids whereas pathological tissue spectra are dominated by proteins. Principal components analysis (PCA) of the spectral data sets belonging to the four different categories showed that scores of factors differentiated between normal and all pathological conditions but gave only poor discrimination among the three pathological states. PCA combined with multiparameter limit tests allow match/mismatch criteria to be applied to test samples when pathologically certified calibration sets are available in each class. It is shown that by this method all the four tissue types could be discriminated and diagnosed correctly. The biochemical differences between normal and pathological conditions of oral tissue are also discussed from spectral differences of the different classes of spectra.

Calibration↗
PubMed2002

Loss of adhesion-regulated proteinase production is correlated with invasive activity in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. However, the cellular and biochemical factors that underlie locoregional and distant spread of the disease are poorly understood. Invasion of OSCC requires multiple cellular events including dissolution of cell-cell junctions, basement membrane attachment, extracellular matrix proteolysis, and migration. METHODS: We evaluated these properties in vitro using premalignant gingival keratinocytes (ppl26) and two OSCC lines (SCC15 and SCC68). Expression of adhesion molecules integrins and cadherins, cytoplasmic intermediate filaments (IF) vimentin and keratin as well as matrix degrading proteins were evaluated. Moreover, regulation of protease production by adhesion molecules was tested. RESULTS: All cell lines contained comparable levels of the epithelial cell-cell adhesion molecule, E-cadherin. Differential expression of cytoplasmic IF was evident between premalignant pp126 cells and OSCC cell lines. Expression levels of the alpha3beta1 integrin, utilized for attachment to laminin-5 and other matrix proteins, was high in SCC68 cells, moderate in SCC15 cells, and low in ppl26 cells. alpha3beta1 integrin clustering up-regulates expression of urinary-type plasminogen activator (uPA) in ppl26 cells via a mechanism involving ERK activation. Both ppl26 and SCC15 cells were responsive to alpha3beta1 clustering, resulting in enhanced uPA expression. However, basal uPA levels were high in SCC68 cells and integrin clustering did not further stimulate uPA production. ERK was constitutively activated in SCC68 cells and treatment of cells with an inhibitor of ERK activation (PD98059) reduced uPA expression. Consistent with the enhanced proteolytic potential, SCC68 cells readily penetrated Matrigel and invasion was blocked by an anticatalytic uPA antibody. CONCLUSIONS: These data suggest that loss of adhesion-regulated proteinase production may lead to elevated pericellular proteinase activity and coincident alterations in cytoskeletal IF protein expression, thereby contributing to the invasive potential of OSCC.

Cadherins↗
PubMed2004

Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis.

BACKGROUND: Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis. METHODS: Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines. RESULTS: Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents. CONCLUSIONS: Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting.

Antineoplastic Agents↗
PubMed2004

Architectural analysis of oral cancer, dysplastic, and normal epithelia.

BACKGROUND: We present a novel, automated, and quantitative approach to evaluate local epithelial tissue architecture based on mathematical graph theory. METHODS: Four hundred forty-one images of three diagnostic classes of oral epithelium (normal, dysplastic, and neoplastic) were analysed. The epithelial compartment was partitioned into exclusive areas associated with each nucleus to approach the theoretical cell extents. The spatial arrangement of cells in neighbourhoods of two sizes was characterised by constructing graph networks based on the cell centroids and recording 29 statistical properties. We analysed 104,627 and 67,590 neighbourhoods of diameters 37.5 and 75 microm, respectively. RESULTS: The discrimination power of the architectural descriptors was evaluated by using discriminant analysis. The best neighbourhood discrimination rate was 75% for normal versus carcinoma. For the pooled data, discrimination into three classes based on largest number of neighbourhoods associated with each class was 100% correct. Case-wise, discrimination rates were 67%, 100%, and 80% correct for normal, premalignant, and malignant. When considering two classes, discrimination rates was 89% (normal) and 100% (malignant) correct, with 71% of premalignant cases assigned to the malignant class. CONCLUSIONS: The results indicate that unbiased and reproducible quantification of tissue architectural features is possible and may provide valuable morphological information for diagnostic purposes.

Cytodiagnosis↗
PubMed2002

Malignant melanoma in the palate of a 3-month-old child.

BACKGROUND: Malignant mucosal melanoma of the head and neck is a rare cancer in adults that carries a grave prognosis. Three mucosal melanomas in pediatric patients have previously been reported. METHODS: We present here the youngest case of malignant mucosal melanoma of the head and neck in a 3-month-old boy. He presented with a 2 x 2-mm-pigmented lesion on the anterior maxillary alveolus. The patient was treated with local excision alone. RESULTS: The patient has remained disease free with regular follow-up for 117 months. CONCLUSION: Based upon this case and the few cases reported in the literature, mucosal melanoma is a much less common disease in children than in adults. Further, juvenile mucosal melanoma displays a benign clinical behavior.

Biopsy, Needle↗
PubMed2005

Pattern of nonspecific (or global) DNA methylation in oral carcinogenesis.

BACKGROUND: Although alterations in nonspecific (or global) DNA methylation (GDM) in specific cells are known to be involved in the process of lung carcinogenesis, similar associations have not been evaluated in other smoking-related cancers of the head and neck. METHODS: We evaluated the status of GDM by using monoclonal antibodies specific for 5-methylcytosine (5-mc) in oral squamous cell carcinoma (SCC) specimens of 48 cigarette smokers who had SCC develop and in 93 age-, race-, and sex-matched smokers who did not. RESULTS: Percentages of cells positive for 5-mc immunostaining of DNA of SCC and dysplastic lesions were significantly higher than those of normal oral epithelial cells from cancer subjects and from noncancer subjects. The degree of DNA methylation was unrelated to DNA content. CONCLUSIONS: The pattern of GDM in oral SCCs is different from that of lung SCCs. The differences in nutrient risk factor profiles that are related to GDM and differential activity of DNA methyltranferases between oral and lung SCCs may explain these observations.

5-Methylcytosine↗
PubMedDate not supplied

Immunohistologic study of mononuclear cell infiltrates in oral squamous cell carcinomas.

Intensity of mononuclear cell infiltrates in 50 oral cancer tissues was evaluated by immunohistochemical stainings. The intensity of the infiltrates was graded into four degrees from marked ( ) to absent (-); and the degree of each infiltrated lymphocyte subpopulation including Leu-3a3b/Leu-2a ratio was matched against clinical and histopathologic features. The vast majority of the infiltrated lymphocytes had antigens which were reactive with anti-T cell antibodies. In T cell subsets, Leu-3a3b+ cells infiltrated clearly (grade ++ or ) in 44 cases, and infiltration greater than grade ++ of Leu-2a+ cells was found in nearly half of the cases (26 of 50). In contrast, B cells (Leu-14+ cells) were obviously detectable in only a few cases, and moderate or marked infiltration of the natural killer (NK) population (Leu-11b+ cells) was not observed. Regarding correlation of T cell infiltrates with clinicopathologic features of the tumors, the degrees of Leu-4+ cell and Leu-2a+ cell infiltration became weak with advancing T stage. Leu-2a+ cells also infiltrated weakly into diffusely invading tumors. Out of 28 cases with no metastasis, 22 cases (78.6%) showed grade ++ approximately of Leu-2a+ cells, and only 4 (18.2%) of 22 cases with lymph node metastasis were clearly positive for Leu-2a+ cells (p less than 0.001). However, Leu-3a3b+ cell infiltration was only slightly related to T stage, metastasis, and to mode of invasion. Therefore, the Leu-3a3b/Leu-2a ratio increased significantly in advanced (T3 + T4) tumors, metastasized cases, or diffuse invasion type.

Antibodies, Monoclonal↗
PubMedDate not supplied

Dual free flap transfer using forearm flap for mandibular reconstruction.

To reconstruct a composite mandibular defect, we have simultaneously transferred a vascularized bone graft or osteocutaneous flap together with a forearm flap. The radial forearm flap, being thin, pliable, and having a long vascular stalk, served as mucosal lining and/or an interpositional flap acting as a vascular bridge. Between 1982 and 1989, we used this procedure in 17 patients with a mandibular defect or deformity which developed following treatment of oral cancer. Our clinical experience has demonstrated that this dual free tissue transfer has many advantages. It is useful for obtaining a good alveolar ridge in patients with a composite mandibular defect. It is applicable in cases where only a single pair of recipient vessels are present and may be useful when the recipient vessels are positioned some distance from the defect.

Adult↗