Untreated Oral Squamous Cell Carcinoma Research Articles

Pain may predict poor prognosis in patients with oral squamous cell carcinoma

We have previously reported that the histologic mode of invasion of oral squamous cell carcinoma (OSCC) is a significant risk factor for pain. Here we sought to determine whether pain is a risk factor for poor prognosis in patients with OSCC. We evaluated the relationships between overall survival rates and clinicopathologic variables, including gender, age, T- and N-stages, pathologic findings, and pain in 109 consecutive patients with untreated OSCC. Of these 109 patients, 40 (37%) reported spontaneous pain. Univariate analysis showed that the overall survival rates of patients with spontaneous pain was significantly lower than those of patients without pain (P = .002). Multivariate analysis revealed that spontaneous pain and N-stage were significant independent predictors of overall survival rates. This is the first report showing that spontaneous pain before treatment may be associated with poor prognosis in patients with OSCC.

Neck recurrence after level I–IV or I–III selective neck dissection in the management of the clinically N0 neck in patients with oral squamous cell carcinoma

Controversy remains regarding extending the level I-III selective neck dissection (SND) to include level IV in the management of the clinically N0 (cN0) neck in patients with oral squamous cell carcinoma (OSCC). Histologic and follow-up data of 87 patients with previously untreated OSCC undergoing I-IV SND and 41 undergoing I-III SND between 2002 and 2006 were reviewed. Of the 98 I-IV SNDs performed, 4 had involvement of level IV. No relationship between tumor variables and level IV involvement was identified. Survival analysis failed to demonstrate a significant difference between I-III and I-IV SND in terms of developing neck recurrence in the 2 years following surgery. Level I-III SND is effective management of the cN0 neck (when coupled with postoperative radiotherapy in selected cases) in patients with OSCC, although it is recommended that a larger prospective study be performed in this field.

Pain is associated with an endophytic cancer growth pattern in patients with oral squamous cell carcinoma before treatment

The origins and mechanisms of pain arising from oral cancer are important. Oral cancer pain impairs a patient's quality of life. This study was undertaken to elucidate significant risk factors associated with spontaneous pain in patients with untreated oral squamous cell carcinoma (OSCC) before treatment. A total of 113 patients (82 men, 31 women; median age, 64 years) with untreated OSCC were examined. Correlations between spontaneous pain in the primary site and sex, age, primary site, TN stage, clinical stage, and clinical growth type of cancer (exophytic or endophytic), as well as the degree of histological differentiation and the histological mode of invasion were evaluated. At the initial examination, 42 (37%) of patients had spontaneous pain. In univariate statistical analyses, reported pain correlated significantly with patient age and the clinical growth type of the cancer, as well as with the degree of histological differentiation and the histological mode of invasion. Multiple logistic regression analysis showed significant correlations between reported spontaneous pain and the clinical growth type of the cancer (P = 0.0003; odds ratio, 9.5; 95% confidence interval, 2.8-32.3), as well as reported spontaneous pain and the histological mode of invasion (P = 0.0026; odds ratio, 4.7; 95% confidence interval, 1.7-12.7). Clinical and histological endophytic growth patterns of OSCC might be significant risk factors for the presence of spontaneous pain before treatment.

Neoadjuvant Chemotherapy with S-1 for Patients with Oral Squamous Cell Carcinoma

S-1, an oral anticancer drug, is comprised of tegafur (a prodrug of 5-fluorouracil) and two biochemical modulators that have effect-enhancing and adverse reaction-reducing activities. Neoadjuvant chemotherapy (NAC) using S-1 has not been reported. Between April 2003 and March 2008, 103 patients with previously untreated oral squamous cell carcinoma (OSCC) received some courses of S-1 NAC (S-1 80 mg/m2/day as the NAC until 1 week preoperatively). Tumor size and histopathologic effect were evaluated before and after treatment. Among 103 cases, 10 cases had complete responses and 53 cases had partial responses (overall response rate [RR], 61.2%). Twenty-two (21.4%) patients had adverse events. Most patients had mild toxicities in the bone marrow and digestive tract (grade 1, 19 cases). Only three patients (2.9%) had grade 2 neutropenia or grade 4 thrombocytopenia. We examined the relationship between the RR and the clinicopathologic behaviors. The RR of the pN2 cases (33.3%) was significantly lower than that of the pN0 cases (69.4%). The RR was not correlated with tumor size, differentiation type, distant metastasis, and the period of administration. The data indicates that S-1 caused only mild toxicity and had highly effective antitumor activity. Furthermore, the RR of S-1 NAC might predict regional lymph node metastasis.

Thymidylate Synthase, Thymidine Phosphorylase and Orotate Phosphoribosyl Transferase Levels as Predictive Factors of Chemotherapy in Oral Squamous Cell Carcinoma

We conducted a clinicopathologic study on protein and mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) using biopsy tissue specimens before treatment. The mRNA levels have been measured in tumor cells microdissected from paraffin-embedded specimens (Danenberg Tumor Profile method: DTP method). We studied the mRNA and protein expression as effect predictive factors in chemotherapy. The subjects consisted of 20 cases of untreated oral squamous cell carcinoma who had undergone chemotherapy with TS-1 (16 males and 4 females, tongue in 8 cases, upper gingiva in 3 cases, lower gingiva in 3 cases, buccal mucosa in 5 cases and floor of the mouth in 1 case). TS gene expressions of the responders were lower than those for the nonresponders. Furthermore, regarding males who were less than 70 years of age, stage I and II, well differentiated type and tongue, TS mRNA expression of the responders were lower than that for the nonresponders. The mRNA expression of OPRT for the male responders was lower than that for the nonresponders. No remarkable difference was observed by immunohistochemistry. In this study, the measurement of the TS levels using the DTP method may potentially act as a predictive factor of antitumor effectiveness.

The Cyclooxygenase‐2 Selective Inhibitor Celecoxib Suppresses Proliferation and Invasiveness in the Human Oral Squamous Carcinoma

Cyclooxygenease-2 (COX-2) expression is a critical factor in inflammation, and plays an important role in defense against exogenous stimuli, while overexpression of COX-2 causes cells to exhibit changes in tumor phenotype. This article attempted to determine the mechanisms underlying the chemopreventive effects of celecoxib on cellular level events, in order to characterize the effects of celecoxib with regard to human oral squamous cell carcinoma (OSCC) cell growth and invasion/migration. In order to determine COX-2 expression levels, we used an OSCC cell line established from surgically resected specimens of an untreated primary OSCC of the tongue, and used reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses with anti-COX-2 monoclonal antibodies. The YD-10B cells represented a highly invasive OSCC cell line, which was found to express the COX-2 protein. Celecoxib inhibited the growth of this OSCC cell line, in a time- and dose-dependent manner. This reduction in cell proliferation was associated with the upregulation of the cyclin-dependent kinase (CDK) inhibitors, p27. In addition, 10 uM celecoxib inhibited cell invasion/migration through the type I collagen matrix by approximately 40% within 24 h. The results of zymography reveal that, in the presence of 10 muL celecoxib, both MMP-2 and MMP-9 enzyme activity decreased by approximately 30-40%. The current in vitro study indicated that the inhibition of proliferation and invasion/migration in OSCC cell line by the COX-2-specific inhibitor, celecoxib, results in anticancerous effects via a variety of cellular and molecular mechanisms. This article also supports the notion that the COX-2 inhibitor may be useful in the inhibition and/or prevention of metastasis.

Hexokinase-II expression in untreated oral squamous cell carcinoma: Comparison with FDG PET imaging

Hexokinase is thought to be one of the key factors of glucose catabolism in the cell. The aim of this study was to investigate the relationship between HK-II expression and 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in human untreated oral squamous cell carcinoma (OSCC). Pre-operatively FDG positron emission tomography (PET) was performed 60 min after FDG injection in all the patients. Maximum standardized uptake value (SUV) was used for evaluation of tumor FDG uptake. Tumor sections were stained immunohistochemically for HK-II. All the tumor sections stained positive for HK-II. Eighteen (95%) tumors in HK-II showed immunostained positive area >50%. HK-II findings revealed eleven (58%) tumors with strong intensity, six (32%) with moderate intensity and two with weak intensity (10%). There was no statistically significant correlation between SUV and the expression of HK-II (p = 0.46). In conclusion, OSCC showed increased FDG accumulation and overexpression of HK-II. However, we did not find any significant relationship between high FDG uptake and overexpression of HK-II in this patient population, and thus other properties need to be evaluated in order to elucidate key factors responsible for FDG activity in OSCC.

The idiosyncratic relationship between diagnostic delay and stage of oral squamous cell carcinoma

Approximately half of patients with oral cancer present with advanced lesions when five-year survival rates are as low as 20%, however, diagnostic delay has repeatedly been found to be unrelated to the stage of oral cancer at diagnosis. The aim of this study was to investigate why diagnostic delay is frequently unrelated to the stage of oral cancer at diagnosis. The odds ratio (OR) of early versus advanced oral squamous cell carcinoma was calculated for 245 consecutive patients with untreated oral squamous cell carcinoma. Being female (OR=0.40; 0.19-0.80; p<0.05) and married (OR=0.27; 0.11-0.66; p<0.01) was predictive of early stage disease. Being non-white (OR=5.42; 1.66-17.67; p<0.01) was predictive of advanced stage disease. There is no evidence that these patient demographics are associated with faster growing tumours, yet it is possible that those who are male, unmarried and non-white may not notice an oral lesion until it is advanced in stage. It is concluded that differences in tumour biology are not a likely explanation for the absence of a delay-stage relationship but instead, a proportion of tumours may be silent until advanced in stage.

The prognostic implications of the surgical margin in oral squamous cell carcinoma

The prime objective of tumour ablation in oral squamous cell carcinoma (OSCC) is the removal, with a ‘margin’ of normal tissue, of the whole tumour. Definition of what constitutes margin involvement varies. This study aims to examine the factors associated with close and involved surgical margins in the management of OSCC. A cohort of 200 consecutive patients with previously untreated OSCC provided the material for the study. Various clinical, operative and pathological parameters were related to the status of the surgical margin, as well as time to recurrence, and survival. Cox regression analysis of the survival was also undertaken. Of the 200 patients 107 (53.5%) had clear margins, 84 (42%) close and 9 (4.5%) involved. Poor correlation was found between the status of the surgical margin and clinical factors, but in contrast high correlation between histological indicators of aggressive disease and close or involved surgical margins. These results imply that close surgical margins in OSCC could be regarded as an indictor of aggressive disease.

A comparison of segmental and marginal bony resection for oral squamous cell carcinoma involving the mandible

Purpose: This study reviews the accuracy of preoperative diagnosis of mandibular invasion by oral squamous cell carcinoma and assesses the role of marginal resection of the mandible in its treatment. Patients and Methods: A retrospective study of a 5-year cohort of 46 patients who underwent mandibular resection for previously untreated oral squamous cell carcinoma was done. Data evaluated included age; sex; site and stage of cancer; preoperative clinical, panoramic, and computed tomography (CT) evaluations; and histologic findings on the resection specimen. The type of mandibular resection (segmental vs marginal) and treatment outcome also were compared. Results: Clinical examination, panoramic radiographs, and CT scans were 78.5% to 82.6% accurate in diagnosing mandibular invasion by squamous carcinoma. Clinical examination and panoramic radiographs are more sensitive than CT scans (86.6% vs 53%), but CT scans were more specific (92.5% vs 80%). The mandible was involved in 65% of patients with segmental resection and 7.6% of patients who had a marginal resection. Nineteen percent of the patients in the marginal resection group died of their oral cancer, two of five patients with local recurrence. Ten percent of patients in the segmental resectiongroup died of oral cancer; no local recurrences were seen. Conclusion: There is no completely accurate method of diagnosing bony invasion of the mandible by oral squamous cell carcinoma. A combination of clinical examination, plain radiographs, and computed tomography (CT) scans may improve the diagnosis. Marginal resection is best reserved for cancers close to the bone with no invasion, minimal cortical invasion, or with early “arrosive” invasion. It is best in the symphysis region. Careful case selection will allow a favorable oncologic outcome with preservation of the mandibular contour.

口腔へん平上皮癌の発育先進部におけるＶＩＩ型コラーゲンの局在

Biopsy specimens from 51 patients with untreated oral squamous cell carcinomas (oral SCC) were examined with monoclonal anti-type VII collagen antibody to study the localization of type VII collagen at the invading edge of tumors and the relation between such localization and clinical and pathological characteristics. The results are summarized as follows.1. According to the immunostaining of type VII collagen, all apecimens could be divided into the following four groups: an intact, continuous linear pattern of immunostaining for type VII collagen around the cancer nests (9 /51, 17.6%); an interruption or attenuation of immunostaining (12/51, 23.5%); a deposition or loss of immunostaining (14/51, 27.5%); and alteration of type VII collagen deposition associated with lymphocyte infiltration into the cancer nests (16/51, 31.4%).2. The immuno-localization of type VII collagen was closely related to the degree of differentiation of cancer cells, the degree of cellular atypia and mitotic index, the mode of cancer invasion, and the degree of lymphocytic infiltration.In conclusion, the results of this study suggest that the immuno-localization of type VII collagen at the invading edge of tumors may reflect the histological malignancy of oral SCC.

Cytokinetic studies of oral cancer cells using bromodeoxyuridine labelling in relation to factors influencing prognosis

Cytokinetics of 27 untreated oral squamous cell carcinomas were evaluated by in vitro bromodeoxyuridine (BrdU) labelling. A mononuclear cell suspension was prepared for the labelling using collagenase and DNase treatment. The labelled cells were visualised by immunofluorescence staining with an anti-BrdU monoclonal antibody. The labelling index (LI%) was calculated by determining the percentage of BrdU labelled cells. The LIs of the carcinomas ranged from 3.8 to 19.2%. The LIs of poorly-differentiated (HG3) tumours were 2-3-fold higher compared with those of well-differentiated (HG1) and moderately-differentiated (HG2) carcinomas. Results also showed statistically significant (P < 0.0005) increases in LIs from nuclear grade 1 (NG1) to nuclear grade 3 (NG3) carcinomas. Higher LIs were observed in stage III/IV (10.82 +/- 4.62; 10.36 +/- 4.90) than those in stage I (6.87 +/- 2.09) and II (7.14 +/- 1.87) carcinomas. A significant (P < 0.0005) difference in LI values was found between the patients with positive and negative lymph nodes. Good correlation (r = 0.77) was exhibited between the LI values and mitotic counts (MC) of the specimens. These results on oral cancer cell proliferation seem to have prognostic implications.

Combined therapy of oral cancer bleomycin and radiation: A clinical trial

A concurrent randomised controlled clinical trial to evaluate a combination of Bleomycin and radiation as against radiation only in the treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras, since 1971. All T3 and T4 previously untreated oral squamous cell carcinomas with N0, N1 and N2 regional nodes, or N3 nodes confined to the submandibular region, without systemic metastases or gross infiltration of the temporal and infratemporal fossa producing total trismus, and in decent general health were eligible for the trial. Patients with gross active pulmonary tuberculosis were excluded, as were recurrent carcinomas. Age, external fungation of growth or radiological bone invasion were no bar. Randomisation was done by the sealed envelope technique. The study group received concurrent fractionated cobalt 60 teletherapy using two opposing fields and 10-15 mg of Intra-arterial or Intravenous Bleomycin. The controls received fractionated cobalt teletherapy and i.v. or i.m. distilled water on the same protocol as the Bleomycin cases. All cases were evaluated double blind 8 weeks after the end of radiation therapy, and were classified as 'favourable response' or 'failure'. The criterion of 'favourable response' was 'total clinical healing of the tumour within the volume of irradiation with no subsequent recurrence within that volume, whatever the length of follow up'. Anything else was reported as a failure. A long term follow up of 3 years is also available. 136 cases have completed the trial. The favourable response in the study group was 77% as against 20.9% in the control group. The differential response is statistically significant. The present study is the fourth in the series of combined therapeutic trials conducted in advanced oral squamous cell carcinoma since 1958. (Krishnamurthi and Shanta, 1963, 1965, 1967 and 1971). A concurrent randomised controlled clinical trial to evaluate the combination of Bleomycin and radiation as against radiation only in treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras since 1971.