Effectiveness of concurrent radiation therapy with UFT or TS-1 for T2N0 glottic cancer in Japan.

The aim of this retrospective study was to compare concurrent radiation therapy (RT) combined with peroral chemotherapy (UFT or TS-1) with conventional RT for T2N0 glottic cancer. Between 1974 and 2005, 153 patients with T2N0 glottic cancer were treated with radiation alone or radiation combined with peroral (UFT or TS-1) or intravenous chemotherapy. All except one patient were treated with 2 Gy per fraction, 5 fractions per week, totaling 60 Gy; and the remaining patient was treated with 1.8 Gy per fraction, 5 fractions per week, totaling 61.2 Gy. Eighty-three patients were concurrently given UFT, 24 were given TS-1, 23 intravenous chemotherapy (mainly cisplatin; the Pt Group), and 23 had no chemotherapy. The 5-year local control rate was 83.4%. Stratified by RT alone (the RT group) and concurrent chemoradiation therapy (the CCRT group), 5-year local control rates of the RT and CCRT groups were 82.7% and 83.4%, respectively (p=NS). Stratified by chemotherapy regimens of the CCRT group, 3-year local control rates of the UFT, TS-1 and Pt groups were 90.1%, 100.0% and 73.4%, respectively. Concurrent chemoradiation therapy using UFT or TS-1 for T2N0 glottic cancer is one of the standard treatments in Japan. Concurrent use of TS-1 could be a breakthrough treatment for T2N0 glottic cancer.

Hypopharyngeal neurinoma: report of two cases.

Hypopharyngeal neurinoma: report of two cases. Acta Otolaryngol 2002; Suppl 547: 100-103. Hypopharyngeal neurinoma is a very rare disease and we found reports of only seven cases in the literature. Laryngomicrosurgery (LMS) and lateral neck exploration are two operating methods for hypopharyngeal neurinoma. Of the seven reported cases, the operating method was mentioned in six: two were operated on using LMS and four using the neck exploration method. It is necessary to select the operating method based on the size of the tumor, the existence of a stem, the risk of bleeding, etc. It is difficult to trace the original nerve of the tumor and this could not be done conclusively in the previous reports.

Expression of Epstein-Barr virus-encoded small nuclear RNA 1 in Japanese nasopharyngeal carcinomas.

An examination was made of the incidence of the Epstein-Barr virus (EBV) genome and its exact localization in 39 cases of nasopharyngeal carcinoma (NPC) in Japanese patients by means of in situ hybridization (ISH) with a digoxigenin-labeled Epstein-Barr virus-encoded small nuclear RNA 1 (EBER1) oligonucleotide probe. Hybridization signals were observed in the nucleus of tumor cells in all 39 NPCs, including keratinizing carcinomas. The signals varied greatly in intensity from case to case and even from cell to cell in the same tumor, but were recognized in most tumor cells in each case. Signals could occasionally be seen in limiting number of infiltrating small lymphocytes but were absent in all tumors of the tongue, midpharynx and hypopharynx. Combined immunohistochemistry-ISH studies indicated that EBER1 signals were restricted to tumor cells positive for cytokeratin. As a result of this study, it is now possible to perform large-scale retrospective analyses using routine formalin-fixed, paraffin-embedded tissue sections and to combine ISH for the EBV genome with immunohistochemistry for cytokeratin to determine the epithelial features of EBV genome-possessing cells. All NPCs were clearly shown to be EBV-infected, thus indicating that EBV is essential for the oncogenesis of NPCs.

Cemento-ossifying fibroma of maxillary and sphenoid sinuses: case report and literature review.

We report a case of cemento-ossifying fibroma (COF) involving the maxillary and sphenoid sinuses and review the literature in order to study the clinical features, imaging findings and histopathologic characteristics of COF. Special care was taken to distinguish this lesion from cemento-osseous dysplasia (COD). It is almost inevitable that differential diagnosis of COD and COF will be complicated by the fact that some pathologic features are shared by both lesions. A combined study incorporating clinical, radiographic and pathologic findings is important in order to ensure an accurate diagnosis. Postoperative follow-up is essential, especially in cases where incomplete removal of the COF was performed.

Clinical impact of using chemoradiotherapy as a primary treatment for hypopharyngeal cancer.

Eighty-eight patients with hypopharyngeal cancer who received chemoradiotherapy as the primary treatment between 1979 and 1997 were investigated. Forty-six patients who received surgery as the primary treatment were analyzed as a control group. There were no statistically significant differences regarding TN classification, tumor stage, tumor site, age or sex between the radiation and surgery groups. The 5-year cumulative survival rate of primary chemoradiotherapy was 47% and this did not differ significantly from that for the primary surgery group. The larynx was preserved in 74% of cases in the primary chemoradiotherapy group, a far better preservation rate than that in the surgery group. After primary chemoradiotherapy, complete remission (CR) was observed in 59% of cases and the average period of CR was 38 months. Among patients with residual tumor, a salvage operation was employed in 31 cases, 13 patients refused to receive surgery and 8 were inoperable. A salvage operation was performed in 35% of all cases and the 5-year cumulative survival rate was 50%. Based on the 5-year survival, primary CR, salvage and laryngeal preservation rates, we conclude that chemoradiotherapy is a good primary treatment for hypopharyngeal cancer.

Treatment of maxillary sinus carcinoma: clinical results using the Kitasato modality.

The conventional therapeutic regimen for maxillary sinus carcinoma consists of dissection of the maxilla, full-dose irradiation and extensive chemotherapy. However, the results obtained with this treatment are often poor. Even when patients recover, their quality of life is significantly reduced as a result of deformity of facial structures and swallowing and articulation dysfunctions. A retrospective analysis of 68 patients with maxillary sinus carcinoma treated with the Kitasato modality between 1975 and 1999 was conducted. All patients underwent pergingival maxillary sinus surgery combined with pre- and postoperative irradiation therapy with standardized total doses of 16 Gy; the postoperative irradiation was given in combination with regional intra-arterial infusion chemotherapy administered via the superficial temporal artery. All visible tumor lesions were removed where possible in order to preserve or facilitate cellular immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.% for Stage IVB.

Assessment of oropharyngeal cancer.

The records of 87 patients with squamous cell carcinoma of the oropharynx, treated between 1971 and 1998 at Kitasato University Hospital, were reviewed with the aim of investigating further directions for oropharyngeal cancer treatment. The patients were divided into four major treatment groups: a radiotherapy group; an operation group; a simultaneous chemoradiotherapy group; and a combination treatment group. The 5-year cumulative survival rates for Stages I-IV were 75%, 78%, 68% and 41%, respectively. None of the T4 cases survived for > 5 years. The survival rates of patients with anterior and posterior wall cancers were higher than those with lateral and superior wall cancers. All patients in the operation group survived for 5 years. The survival rates for the combination treatment, radiotherapy and chemoradiotherapy groups were 80%, 57% and 52%, respectively. The 5-year cumulative local control rates for T2-T4 tumors were 61%, 58% and 0%, respectively. The combination therapy (80%) and chemoradiotherapy (66%) groups had significantly higher local control rates than the radiation group (33%). The 5-year cumulative regional control rate according to N classification was approximately 80%, except for N2 lymph nodes, for which only 60% of patients were free of regional recurrences. Approximately 15% of patients with oropharyngeal cancer had either distant metastases or double cancer. We conclude from this review that simultaneous chemoradiotherapy is a good initial therapy for Stages Tl-T3 oropharyngeal cancer. However, for T4 tumors, further combinations of both chemoradiotherapy and surgery and the development of new anticancer drugs for use in chemoradiotherapy, immunotherapy or gene therapy may be needed.

Carcinoma of the nasopharynx: analysis of treatment results in 91 patients.

The outcome of 91 patients (69 males, 22 females; age range 16-82 years) with nasopharyngeal carcinoma treated in our hospital between 1971 and 1999 was evaluated. Factors that appeared to influence prognosis were assessed using the Kaplan-Meier method. The cause-specific cumulative 5-year survival rate for the entire study population was 61.2%. The 1997 International Union Against Cancer classification was used for disease staging. The 5-year survival rates were as follows: 66.7% (n = 3) for Stage I; 100% (n = 2) for Stage IIA; 90.9% (n = 11) for Stage IIB; 78.8% (n = 25) for Stage III; 53.0% (n = 29) for Stage IVA; 37.5% (n = 16) for Stage IVB; and 20.0% (n = 5) for Stage IVC. The disease-free cumulative 3-year survival rates of the patients classified based on initial therapy were as follows: radiation alone, 50.0% (n = 28); combined radiotherapy and chemotherapy that included an undefined anti-cancer drug, 67.2% (n = 39); combined radiotherapy and chemotherapy that included carboplatin (CBDCA), 92.3% (n = 19). These results showed a statistically significant difference (p = 0.043; log-rank test). Stage IVC patients were excluded from the analysis. We conclude that combined therapy, including chemotherapy with CBDCA, is necessary for the treatment of nasopharyngeal carcinoma. In terms of radiation therapy, a field covering the bilateral cervical regions seemed to produce favorable results, even if cervical node metastasis was not confirmed by palpation at the first hospital visit. Key words: carboplatin, chemotherapy,

Treatment effects in patients with squamous cell carcinoma of the oral cavity.

A total of 221 patients (155 males, 66 females; stage I, n = 55: stage II, n = 58; stage III, n = 57; stage IV, n = 51) with squamous cell carcinoma of the oral cavity were studied. Tumor localization was as follows: cancer of the tongue, n = 161; cancer of the oral floor, n = 28; cancer of the hard palate, n = 12; cancer of the buccal mucosa, n = 11; and cancer of the gingiva, n = 9. In order to compare the effect of different treatments, three major treatment groups were defined, namely a surgery group, a radiotherapy group and a combination treatment group. Five-year cumulative survival rates showed significant differences between stage classifications (stage I = 91%, stage II = 73%, stage III = 63%, stage IV = 47%; p < 0.01) but not between tumor sites. The 5-year cumulative survival rate was highest for oral floor cancer (80%). In the early-cancer group, the 5-year cumulative survival rate for the surgery group (92%) was significantly higher (p < 0.05) than those for both the radiation (69%) and combination (71%) groups. In the advanced-cancer group, the 5-year cumulative survival rate for the surgery group (74%) was significantly higher (p < 0.05) than those for both the radiation (37%) and combination (51%) groups. No significant difference in regional control rates was observed between the treatment groups. Five-year regional control rates were 86% for cervical untreated patients with T1N0 tumors and 60% for cervical untreated patients with T2N0 tumors. Fourteen N0 cases were treated with neck dissection. Cervical metastasis was found pathologically in 2/14 (14%) of these cases. The 5-year survival rate for patients with cervical recurrences after primary tumor resection was 70% (n = 15). In contrast, the 5-year survival rate for patients with both primary tumor resection and neck dissection was 74% (n = 14) but no significant difference was observed between these 2 groups.

Three-dimensional analysis of supracricoid hemilaryngopharyngectomized hypopharyngeal cancer.

The aims of this study were to demonstrate the technical aspects of processing high-resolution three-dimensional (3D) images and to describe the value of this approach for studying partially removed hypopharyngeal cancer. Supracricoid hemilaryngopharyngectomy was conducted in three sinus-type hypopharyngeal cancers as a salvage operation. A histopathologic study was conducted in order to fully examine the resection margin of the surgical specimens and to ensure the credibility of our case selection. The morphological features of each specimen were analyzed and demonstrated using 2D and 3D settings. Whole-mount serial histological sections were developed from the surgical specimens and 3D images were reconstructed based on these sections. In each case the 3D images demonstrated the characteristic patterns of cancer extension, such as superior extension under the intact epithelium and the formation of multiple skip lesions. The overall resection margin was proven to be free of cancer in all three cases. In conclusion, 3D study was useful for evaluating the overall resection margin of surgical specimens and provided valuable information for use in future follow-up. Using this technique, the morphological findings from serial sections are more comprehensive and impressive. 3D reconstruction is and will be a crucial modality for studying the morphological behavior of hypopharyngeal cancer.

Limited surgery for cancer of the larynx and hypopharynx: options and consequences.

We reviewed surgical options for laryngeal preservation (limited surgery) in laryngeal and hypopharyngeal cancers and the consequences of the options. Of 44 patients with laryngeal cancer, 11 (25%) received limited surgery and 33 (75%) received total laryngectomy. The survival rates were 91% for the limited surgery group and 73% for the total (radical) surgery group. Of 31 patients with hypopharyngeal cancer, 7 (23%) received limited surgery and 24 (77%) received total laryngopharyngectomy. The survival rates were 53% for the limited surgery group and 40% for the total (radical) surgery group. The survival rates associated with limited surgery were thus better than those for total (radical) surgery for cancers of both the larynx and hypopharynx. This was attributed to the limited surgery group comprising well-selected patients with confined lesions. Organ preservation surgery should be technically simple, reliable in terms of its functional impact and, above all, should not jeopardize the patient's survival. Supracricoid subtotal laryngectomy with cricohyoidoepiglottopexy or cricohyoido-pexy has great potential for laryngeal preservation and will become the major limited surgery modality for treating cancer of the larynx. Limited surgery, however, needs to be performed with great care and is indicated only for very well-selected patients with cancer of the hypopharynx.

Clinical review of Wegener's granulomatosis.

The prognosis of Wegener's granulomatosis (WG) improved following the introduction of immunosuppressant agents. We, however, still experience some difficult cases that are resistant to treatment. Early diagnosis and treatment may improve the prognosis of WG. We reviewed patients with WG attending the Department of Otorhinolaryngology, Kitasato University Hospital. Of the 13 patients reviewed, 5 are still alive. A definite diagnosis was difficult to make without the presence of certain characteristic features. Recently, cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) has gained importance in the diagnosis of WG and five of our patients were positive for c-ANCA. Close long-term follow-up of WG is recommended: remission was observed in two of our patients and side-effects of the treatment were identified in four.

Detection of epstein-barr virus in nasal T-cell lymphoma.

The close relationship between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has frequently been reported. However, the status of the infection, either lytic or latent, is obscure. This study involved 16 patients with NTL. Phenotypes of lymphoma cells were examined by immunohistochemical staining using CD3, CD4, CD8, CD20 and CD45RO monoclonal antibodies. EBV-encoded small nuclear RNA (EBER)-1 and EBV NotI tandem repeat region were detected by reverse transcription, using a rapid (< or = 60 min) in situ hybridization technique. Tumor cells expressed at least one T-cell marker, such as CD3, CD4, CD8 and CD45RO. CD20 was not detected in any of the cases. EBER-1 was identified in all cases; no Notl tandem DNA repeat was demonstrated. All cases demonstrated a T-cell phenotype. These data suggest that NTL is associated with EBV infection in the latent phase.

Head and neck malignancy statistics at Kitasato University.

We analyzed and reported on those patients with head and neck (H&N) malignancies who had visited our university within the last 30 years. The number of H&N patients registered per year has gradually increased with time and approximately 120 new patients have been registered annually in recent years. Age-adjusted morbidity has also increased gradually, from 7.06 to 10.55 per 100,000 citizens, in recent years. The population of Sagamihara city has gradually increased in parallel over the same period. Cancers of the pharynx, larynx and oral cavity are the three major H&N tumors. Squamous cell carcinoma was the most commonly seen pathological diagnosis, followed by malignant lymphoma. The 5-year crude survival rate for all patients was 50%. It is suggested that improving the survival rates of cancers of the oral cavity, nasal cavity and paranasal sinuses should be a prerequisite, in order to diminish H&N tumor deaths in Japan. A satisfactory survival rate for cancer of the paranasal sinuses has been achieved at Kitasato University and it is hoped that our modality will further prevail in the near future. Cancer of the oral cavity is visible and can be detected by a simple clinical examination. As H&N surgeons it is necessary to educate all physicians as to the importance of early detection of H&N tumors. We also need to encourage the public to reduce smoking and drinking in order to prevent a further increase in the number of H&N patients. Our assertions are based on the fact that the number of H&N patients in 2050 is estimated to be three times greater than that at present due to the increase in the population of elderly people (assuming the morbidity rate remains constant). Key words: alcohol, cancer trends, morbidity, predictions, tobacco.

Clinical study of T1a glottic-type cancer.

Laser surgery is indicated for T1a glottic cancer when the tumor is localized in the membranous portion without involvement of the anterior commissure or cartilagenous portion. Treatment for T1a glottic cancer was reviewed with particular attention to indications, prognosis and the pattern of recurrent cases. A group treated with laser surgery showed 5-year local control, larynx conservation and survival rates of 90.5%, 100% and 100%, respectively. Corresponding values for a group treated with radiotherapy were 92.2%, 98.0% and 100%, respectively. In three cases of recurrence, laser surgery was carried out as second and third treatments. These cases met the above-mentioned indications for laser surgery at the time of recurrence and re-recurrence. Of the three patients, two have survived for > or = 6 years without further recurrences. Provided strict selection criteria are applied, laser surgery is indicated in some cases of recurrence.

Clinical review of autopsy cases that succumbed to head and neck malignancies.

We investigated autopsy cases that had succumbed to head and neck malignancies in the light of the relationships between locoregional tumors and distant metastasis, between the frequency and site of distant metastasis and between the occurrence of locoregional tumors/distant metastasis and the cause of death. Of the 203 cases autopsied at the Kitasato University Hospital between 1972 and 1999, 174 had epithelial tumors and 29 had non-epithelial tumors (malignant lymphoma in 20/29). In terms of epithelial tumors, 107 patients (61%) had locoregional disease and 101 (58%) exhibited distant metastases; 39 cases (28%) had distant metastasis without locoregional tumors. Although the cause of death was mostly as the result of locoregional disease, death related to distant metastasis was also frequently observed. Of the 20 cases with malignant lymphoma, 17 had distant metastases and only 2 of them manifested tumors in the primary region. All 17 patients with distant metastases showed tumors in the distant lymph nodes, with a relatively high occurrence of metastasis to the gastrointestinal tract. Key words: cause of death, distant metastasis, locoregional tumor.

Clinical review of thyroid malignant tumor.

We reviewed the files of 120 patients with thyroid malignant tumor treated in our department between July 1971 and December 1996. Clinical features, pathological diagnosis, radiographic findings, treatment and prognosis were studied. The number of patients treated gradually increased over time in both the otorhinolaryngology and surgery departments. Papillary carcinoma (n = 101) was the most common pathology, followed by follicular carcinoma (n = 16). Both 5- and 10-year survival rates were 92.7% for the entire group, 93.8% for cases of follicular carcinoma and 92.1% for cases of papillary carcinoma. Although thyroid tumor is undoubtedly one of the malignant head and neck tumors associated with an excellent prognosis, some patients remain resistant to cure in the long term. Some tumors are highly malignant and are difficult to control. The management of these patients is an important subject of future research.

Malignant fibrous histiocytoma of the nasal cavity and paranasal sinuses: review of the last 30 years.

The clinical and pathologic features of four patients with malignant fibrous histiocytoma of the maxillary sinus were studied. All patients were male, with an age range of 43-71 years at the time of diagnosis. The main symptoms were pain in the facial region, swelling of the cheek and nasal bleeding. Pathologically, three patients were subclassified with the striform-pleomorphic type of malignant fibrous histiocytoma and one with the myxoid type. All patients were operated on and received various combinations of pre- and postoperative irradiation and intra-arterial chemotherapy given via the temporal artery. In the patient with the best prognosis, tumor extension within the maxillary sinus was minimal. Two patients developed local recurrences and died. None of the patients developed locoregional lymph node or systemic metastases.

Clinical study of benign lesions in the oral cavity.

This retrospective study was designed to investigate the detailed clinical features of benign oral diseases. A total of 792 patients with benign oral lesions were treated at Kitasato University Hospital over a 27-year period. Benign oral lesions were classified into nine groups as follows: epithelial proliferating lesions (n = 234); fibroma-like lesions (n = 150); cysts and cyst-like lesions of the minor salivary glands (n = 140); ranulas (n = 64); angiomas (n = 62); inflammation/ulcer/granulation lesions (n = 56); pyogenic granulomas (n = 44); pleomorphic adenomas (n = 23); and others (n = 19). The characteristics of all these benign oral lesions are summarized. We believe that these characteristics will be helpful for physicians in their daily clinical examinations.

Prognostic factors of head and neck adenoid cystic carcinoma: quantitative morphological analysis of 19 cases.

This quantitative study was prompted by concerns regarding the clinical and histopathologic correlation of adenoid cystic carcinoma (ACC). We reviewed the clinical and histopathologic data of 19 cases of ACC in the head and neck region treated during the last 25 years. An image analyzing system was employed for quantitative analysis. Each specimen was observed microscopically at 100 x magnification, by two of the authors, the area of pure cellular component in five randomly selected fields was measured and the averaged cellular ratio per field was calculated as a percentage and then correlated with the behavior of the tumor. The cellular ratio was 66% for the 8 patients who died of disease and 47% (at 3-year follow-up; n = 9) and 58% (at 10-year follow-up; n = 4) for the 11 patients who survived without evidence of disease. For all of the patients who developed distant metastasis the cellular ratio was > 60%. The results of this quantitative study did correlate, to some extent, with the patients' clinical behavior. Although non-quantitative clinical and histological criteria of ACC have been reported to correlate with clinical behavior, it is important to thoroughly understand these criteria and also to combine multiple criteria in order to manage head and neck ACC.