Search

当科では上顎洞扁平上皮癌に上顎試験開洞減量術と浅側頭動脈経由の動注化学放射線治療および根治手術をあわせた集学的治療を施行している。今回この治療の有効性を検証するために1997年1月から2007年12月までの上顎洞扁平上皮癌37症例につき，死因特異的3年生存率，再発率を検討した。生存率はT3症例で89%，T4a症例で66%，T4b症例で29%であった。動注化学放射線治療を施行し一次根治を得られた28例の原発巣再発率はT3症例は0%で，T4a症例は44%，T4b症例は67%であった。原発巣再発後の制御率はT4a症例で43%，T4bは0%であり，T4症例における原発巣再発をさらに減じうる集学的治療の確立が重要であると考えた。

In treatment of squamous cell carcinoma of the mouth floor, we reviewed 26 cases-25 men and one woman from 38 to 83 years old-treated from January 1997 to January 2006 in our institution. Three-year survival rate was 88% in all cases, 100% in stages I and II, and 67% in stages III and IV. Overall sites recurrence was 38%, 17% in primary recurrence, 13% in cervical recurrence, and 8% in distant metastasis. Primary recurrence was salvaged 25% of patients and cervical recurrence, 67%, respectively. In non-operative cases for the neck, cervical recurrence was 8% and salvaged by neck dissection, so we concluded that elective neck dissection was not necessary.

当科で一次治療を行った上咽頭癌38例の治療成績を検討し予後因子の解析を行った。上咽頭癌全体の治療成績は，疾患特異的3年生存率（以下3生率）が50%，3年局所・所属リンパ節制御率が58%と不良であった。年齢別の検討では高齢になるに従い生存率は低下傾向にあったが有意差はなかった。原発巣（以下T）別でみても生存率に有意差はなくTが進行するに従い局所・所属リンパ節制御率が低下する傾向も認めなかった。頸部リンパ節（以下N）別ではNが進行するに従い生存率・制御率ともに低下傾向にあったが有意差はなかった。病期別でも生存率に有意差はなかった。一方組織別でみるとWHO type 1はtype 2・3にくらべ有意差はないものの生存率が低い傾向にあり，局所・所属リンパ節制御率はtype 1が有意に低かった。以上の解析から，年齢・T・N・病期・組織型の中に予後不良因子はなかったが，組織型WHO type 1の局所・所属リンパ節制御率は有意に不良であるという結果となった。

同一の切除範囲や同一の再建皮弁における構音機能を検討するために，舌可動部半切術，大胸筋皮弁による再建術を行った症例で術後6ヵ月以上経過している9例を対象とし，皮弁の形状分類と，舌の可動性の評価を行い，これらと発語明瞭度との関連を検討した．その結果，発語明瞭度は隆起型71.6％，平坦型84.4％，陥凹型34.1％であり，陥凹型は低い傾向を示した．舌の可動性は，前方可動性，側方可動性ともに，隆起型では発語明瞭度と相関する傾向を認めたが，陥凹型では相関しなかった．皮弁の形状が舌の可動性よりも発語明瞭度に与える影響が大きい可能性があり，皮弁の形状は平坦型以上の隆起が必要と考えられた．

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to treat cancer patients. However, the presence of drug resistant tumor cells may cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is also responsible for the degradation of 5-FU. In this study, we examined whether DPD expression affects the cytotoxic activity of 5-FU against head and neck squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The effect of DPD expression on in vitro cell growth, cell cycle and 5-FU cytotoxicity was examined. In addition, we also evaluated the association between DPD expression and the proliferation of tumor cells in surgical specimens, and prognosis of the patients with HNSCC. DPD overexpression decreases the cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell proliferation and does not seem to have prognostic value in HNSCC. The present results strongly indicate that DPD expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of personalized chemotherapy including the prediction of response and adverse effects.

We evaluated the efficacy of multimodality therapy for nonsquamous cell carcinoma (salivary carcinoma) of the nasal and paranasal sinuses. We retrospectively analyzed 28 patients with nonsquamous cell carcinoma of the nasal cavity and paranasal sinuses between 1972 and 2005. Primary sites were the maxillary sinus in 20 patients, ethmoidal sinus in 1, and the nasal cavity in 7. Pathology included adenocarcinoma in 5, mucoepidermoid carcinoma in 4, adenoid cystic carcinoma in 18, and adenosquamous carcinoma in 1. Five-year survival was 55% in all cases, 50% in the maxillary and ethmoidal sinuses, and 71% in the nasal cavity. Adenoid cystic carcinoma recurrence persisted over the five years following primary treatment and salvage after recurrence was 0%. Multimodality therapy decreased primary-site recurrence more than nonmultimodality therapy. Multimodality therapy thus appears useful in the primary treatment of nonsquamous cell carcinoma in the nasal cavity and paranasal sinuses.

進行舌扁平上皮癌の治療成績向上を目的とし，1997年以降当科では術前動注化学放射線治療および根治手術をあわせた集学的治療を施行している。今回その治療法の有効性を検証するために1997年1月から2005年12月までの進行舌扁平上皮癌症例につき，治療法の違いによる死因特異的生存率，再発率を検討した。生存率は集学的治療例の病期IIIは86%，病期IVでは68%であり，それ以外の治療が行われた症例はそれぞれ80%，50%であり，有意差は認めなかったが，集学的治療症例のほうが良い傾向であった。また一次根治症例の原発巣，頸部再発では集学的治療例は22%であったが，それ以外の治療が行われた症例では55%であり，両者に有意差はないものの集学的治療例のほうが少ない傾向にあった。また集学的治療で一次根治できた病期III症例は術後治療の有無に関係なく原発巣，頸部再発は認めなかったが，集学的治療で一次根治できた病期IV症例は術後治療を行っていても原発巣，頸部再発を30%に認め，術後治療内容の変更を考慮すべきであると考えた。

Aims: Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC). Methods and results: Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein–Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P

2000年1月から2006年12月までの6年間に，当科で一次治療を行った頭頸部扁平上皮癌の病期III，IV症例の277例中65歳以上の症例117例を対象とし，75歳以上の後期高齢者の有効な治療を検討するために，65歳以上75歳未満の前期高齢者を対照として臨床的検討を行った。合併症は両群ともに多く，高血圧，心血管疾患を多く認めた。後期高齢者はPerformance statusが悪く，より進行した症例が多かった。一次根治できた症例75例の3年粗生存率は前期高齢者68%，後期高齢者57%で，有意差は認めず，死因特異的3年生存率では，前期高齢者78%，後期高齢者75%であった。平均在院日数，治療後の退院先や再発率にも両者の差を認めず，後期高齢者であっても前期高齢者と同様に一次根治を目指すことが望ましいと考えた。

標準的治療とは，異なる治療法の中のより優れた治療を示し，診療ガイドラインは，「特定の臨床状況の下で，適切な判断や決断を下せるよう支援する目的で体系的に作成された文書」と定義されている。いずれもEvidence based medicine (EBM)に基づくものであることが重要である。下咽頭癌に対するガイドラインは，米国や英国ですでに発表されているが，わが国では未だ案の段階であり，良質のevidenceが少なく，多施設の協力によるevidenceの集積が急務である。当科での下咽頭扁平上皮癌177例の検討では，化学放射線同時併用療法は生存率と喉頭温存率の改善に有用であった。しかし，T進行例における喉頭温存率の改善は，不十分であり，今後，より適切な薬剤・投与法を開発する必要があると思われた。

頸部郭清術は頭頸部がんの外科治療の基本術式といえる。米国では2002年に頭頸部外科の関連学会が中心となって頸部リンパ節の分類と頸部郭清術の名称に関する新提案がなされた。本邦では系統的かつ統一性のある定義づけが行われておらず，治療法の比較検証のための術式の記載法の統一のみならず個別的治療からも頸部郭清術の系統的分類と命名法が必要とされる。隣接臓器との整合性と欧米の分類との互換性を図り，新たなる系統的分類と呼称を提唱した。頸部リンパ節の分類としては，基本的に日本癌治療学会リンパ節規約を用いて3つの基本領域とその他の領域に分類し，さらに基本領域に小分割として亜区域を設けた。術式は郭清範囲により全頸部郭清術と選択的頸部郭清術の名称を用いて分類した。術式の簡略表記法は郭清された領域と切除された非リンパ組織の2つの要素を略字で表記した。

Background. Although sinonasal inverted papilloma (IP) is a rare benign tumor, it has a tendency to recur and is sometimes associated with squamous cell carcinoma (SCC). Therefore, postoperative long-term follow-up of these patients is recommended. We previously reported that serum SCC antigen might be a useful tumor marker for sinonasal IP. In this study, we investigated whether serum SCC antigen level has a correlation with disease status and is useful in the early detection of recurrent disease. Methods. Blood samples for the analysis of serum SCC antigen were taken from 28 IP patients before and after surgical treatment. Results. Twenty-five (89%) of 28 cases showed evaluated serum SCC antigen levels above the upper limit. This marker level decreased in all cases after surgical resection. Four of these patients had a recurrence. None of the patients with recurrent tumor showed symptoms at the time of detection of their recurrent tumor, and recurrence was discovered from elevated levels of SCC antigen. Conclusions. Serum SCC antigen level has a correlation with disease status of IP and has a potential to serve as a useful tool for monitoring the course of disease. SCC antigen is a reliable tumor marker in the management of sinonasal IPs. © 2004 Wiley Periodicals, Inc. Head Neck27: 44–48, 2005

A retrospective review of 145 previously untreated patients with squamous cell carcinoma (SCC) of the tongue was performed. All these cases were with no regional and distant metastasis. They were treated in the Kyushu Cancer Center between March 1972 and July 1998, and received interstitial irradiation, an operation, or an operation or interstitial irradiation after arterial infusion chemotherapy via superficial temporal artery combination external irradiation as initial treatment for primary lesion (tongue). The scope of external irradiation included the submandibular nodes and the upper jugular nodes. They did not receive prophyiactic neck dissection except the cases requiring reconstruction of the tongue and floor of the mouth. The five-year survival rate (5YSR) calculated by the Kaplan-Meier method was 82%. Recurrence occurred in 59 patients, of which 21 cases were local, 37 cases were regional and one case was distant recurrence. The 5YSR of local recurrence cases was 61%, that of regional recurrence cases was 56%, and that of distant recurrence cases was 0%. Neck dissection was performed for 35 patients of 37 regional recurrence cases, of which 31 patients were salvaged and 4 patients were uncontrollable. The regional control rate by neck dissection after regional recurrence was 89%. The N stage of the uncontrollable 4 patients was more than N2b. These results suggest that the early detection of regional recurrenceis important.

To evaluate the diagnostic value of gadolinium-enhanced dynamic magnetic resonance (MR) imaging of salivary gland tumors and correlate the MR imaging and histopathologic findings.Thirty-three salivary gland tumors in 29 patients were examined preoperatively at gadolinium-enhanced dynamic MR imaging. There were 22 benign and 11 malignant tumors. Dynamic contrast material-enhanced MR images were obtained for 5 minutes. Time of peak enhancement (T(peak)) and washout ratio (WR) were determined from time-signal intensity curves (TICs). Microvessel count and cellularity-stromal grade were evaluated histopathologically. The strengths of correlations between T(peak) and microvessel count and between WR and cellularity-stromal grade were statistically analyzed. Statistical analysis was also performed to determine whether any differences among the various histopathologic tumor types existed [corrected]. In a validation study, 13 salivary gland tumors in 13 patients were examined consecutively.At a T(peak) of 120 seconds, malignant tumors could be differentiated from pleomorphic adenomas but not from Warthin tumors. A WR of 30%, however, enabled differentiation between malignant and Warthin tumors. Classification of TICs on the basis of a T(peak) of 120 seconds and a WR of 30% had high sensitivity (91%) and specificity (91%) in the differentiation of benign and malignant tumors. Correlations between T(peak) and microvessel count (P.0001, rho = -0.800) and between WR and cellularity-stromal grade (P =.0105, rho = 0.572) were significant. The validation study also yielded high sensitivity (100%) and specificity (80%) in the differentiation between benign and malignant tumors.Gadolinium-enhanced dynamic MR imaging is useful for differentiating benign from malignant salivary gland tumors.

AIM: To clarify CT and MR features of nasopharyngeal carcinoma (NPC) in children and young adults. METHOD: CT and MR findings of 13 patients (30 years old or younger) with a histopathologic diagnosis of NPC were reviewed. RESULTS: Skull base invasion (12/13), lymphadenopathy (10/13), and infiltrative growth (8/8) were common findings. The signal intensity of tumours was slightly higher than that of muscles in six cases and isointense to that of muscles in two cases on T1-weighted images; it was higher than that of muscle and lower than that of cerebellar grey matter on T2-weighted images in all cases. Internal signals were homogeneous in both pre- and post-Gd-enhanced MR images in all cases. CONCLUSIONS: Despite its rarity in this age group, NPC should be included in a differential diagnosis when CT and MR imaging reveal these features. Yabuuchi H., et al. (2002). Clinical Radiology57, 205–210.

BACKGROUND Inverted papilloma (IP) is a frequent benign sinonasal tumor that is characterized histologically by squamous metaplasia, epithelial acanthosis, and hyperplasia of the nasal epithelium. Because of its high recurrence rate and malignant transformation potential, careful long-term follow up is necessary. METHODS The purpose of the current report was to study the expression of squamous cell carcinoma (SCC) antigen in sinonasal IPs and to evaluate the usefulness of SCC antigen as a biologic marker for the follow-up of patients with sinonasal IP. The expression of SCCA1 in three sinonasal IP cases, three sinonasal SCC cases, and cases of normal nasal epithelium were examined by Western blot analysis, and the SCCA1 expression pattern in 31 IP specimens and 4 carcinoma in IP specimens were evaluated immunohistochemically. The serum levels of SCC antigen in 11 patients with sinonasal IP also were analyzed. RESULTS SCCA1 was overexpressed in all three sinonasal IP tissues compared with sinonasal SCC tissues or normal nasal epithelium. SCCA1 cytoplasmic immunoreactivity was detected in the suprabasal epidermal keratinocytes of all 31 sinonasal IP cases. In the four carcinoma in IP specimens, SCCA1 expression in the papillomatous lesion was more intense than in the cancerous lesion. The serum SCC antigen level was high in 10 of 11 patients with IP (91%) and significantly decreased after surgical resection of the tumors. CONCLUSIONS The results of the current study indicate that SCCA1 frequently is overexpressed and may play a biologic role in the development of sinonasal IPs. Serum SCC antigen may be a useful biologic marker in patients with sinonasal IP. Cancer 2002;94:152–8. © 2002 American Cancer Society.

Squamous cell carcinoma (SCC) antigen has been used for the management of SCC arising in various cites including head and neck region. However, the true mechanism of the elevation of this protein in the serum of patients with SCC is still unknown. SCC antigen belongs to the superfamily of serine protease inhibitors. Recently, molecular studies show that serum SCC antigen is transcribed by two nearly identical genes (SCCA1 and SCCA2), and is mainly produced by SCCA1. The objective of this study is to clarify the mechanism of the elevation of SCC antigen in oral tongue SCC patients and to identify cells histologically, which are responsible for serum SCC antigen production. In this study, we examined SCCA1 expression in a series of four head and neck SCC (HNSCC) cell lines, and found that all expressed equal to low SCCA1 protein as compared with the normal human oral keratinocyte. Using the double immunohistochemical technique to examine the expression pattern of SCCA1 in 86 cases of oral tongue squamous cell carcinoma, SCCA1 immunostaining was observed in the cytoplasm of cancer cells and T-lymphocytes peripheral to cancer cells. We also compared the clinicopathological features including serum SCC antigen level of the oral tongue SCC cases with the immunohistochemical SCCA1 expression pattern, and found that elevated serum SCC antigen level was significantly correlated with SCCA1 expression not in cancer cells, but in T-lymphocytes peripheral to cancer cells. These results suggest that T-lymphocytes peripheral to cancer cells may be responsible for serum SCC antigen production in HNSCC patients.

The need for improved medical treatment quality, efficient use of medical finances, and shortening of hospitalization have helped disseminate team medical care using a clinical path. In otorhinolaryngological head and neck surgery, medical facilities have created a clinical path for tonsillectomy, tympanoplasty, and radical sinus maxilectomy and ethmoidectomy. Such a path has not been made, however, for head and neck tumors. We created a clinical for thyroid tumor, then evaluated its advantages and disadvantages. We started the clinical path for benign thyroid tumors in April 2000 for 14 thyroid patients considered benign before surgery. In some cases, the clinical path was slightly changed to allow for delayed drain extraction or increasing the number of blood pressure measurements due to complications of hypertension. No variation was so major, however, that the clinical path had to be canceled. Its advantages were (1) average hospitalization shortened from 18.7 days to 14.5 days, and (2) the clinical path was useful for educating new staff. Since changes are more likely to occur in cases of tumors, medical staff and patients must understand that the clinical path basically represents the standard or average and may depend greatly on the individual condition. Since the clinical path represents the standard or average at a certain time point, it must be revised. A clinical path is, even so, useful in the treatment of tumor.

Subjects were 16 patients--5 men and 11 women aged 46-82 years (mean: 61 years)--with malignant melanoma of the head and neck treated at our clinic from 1972 to 1988. Histologically, 1 subjects was amelanotic and 15 melanotic type. Primary lesions were 10 involving the nasal cavity, 2 the paranasal sinus, 2 the gingiva, 1 the lip, and 1 primary unknown. They were treated with or without multimodal surgery, radiation, chemotherapy, and immunotherapy. Of 12 treated using local surgery, local recurrence was seen in 6 in 7 areas. Two-year survival was 44% and 5-year survival 22%. The prognosis of malignant head and neck melanoma is poor but has gradually improved due to preoperative decisions on disease spread and the introduction of multimodal therapy.

Background A relatively high failure rate in the therapy of patients with early oral tongue squamous cell carcinomas (SCCs) is evidenced by untreated clinically negative neck lymph node metastasis. It is important to predict the malignant potential of oral tongue SCC in stage I and II patients, because the development of lymph node metastasis directly affects the prognosis of the patients. Methods We evaluated maspin expression immunohistochemically in patients with stage I and II oral tongue SCCs and determined whether the expression level may be a useful factor in predicting metastatic potential and prognosis of these SCCs. Results Clinical follow-up data showed a longer disease-free interval and overall survival periods for tumors immunohistochemically positive for maspin than for tumors negative for maspin, with the difference in disease-free interval being statistically significant (p = .01). The absence of maspin expression was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis (p = .03). Conclusions Decreased maspin expression may be a significant factor associated with the metastatic potential of stage I and II oral tongue SCCs. © 2001 John Wiley & Sons, Inc. Head Neck 23: 962–966, 2001.

唾液腺腫瘍における穿刺吸引細胞診, 術中迅速組織検査の成績について検討を行った。対象は1980年から1998年までに国立病院九州がんセンターにて手術を行い, 永久組織診断の確定した唾液腺腫瘍症例51例である。術中迅速組織検査はこのうちの33例に対して行った。穿刺吸引細胞診の悪性に関する感受性は70%, 特異性は93%, 正診率は82%であり, 組織型の正診率は43%であった。術中迅速組織検査も施行した33例において, 悪性に関する感受性, 特異性, 正診率, 組織型の正診率は, いずれも穿刺吸引細胞診 (62%, 90%, 79%, 48%) に比べて術中迅速組織検査 (77%, 100%, 91%, 85%) の方が優れていた。術中迅速組織検査においても, 粘表皮癌低悪性型, 腺房細胞癌の組織型推定は困難であったが, その他の腫瘍に対する術式決定には有用な検査法と考えられた。

The overall survival rate (OSR) of 36 patients with nasopharyngeal carcinomas (NPC) treated at Kyushu University hospital between 1983 to 1992 was analyzed. As primary treatment, 16 patients received a combination therapy of 5-fluorouracil, vitamin A, and radiation (FAR therapy); two patients received radiotherapy only; 18 patients received FAR therapy plus adjunctive systemic chemotherapy consisting of cisplatin and peplomycin. The radiation dose to the nasopharynx was 6000 to 7050 cGy while that to the neck was 4000-6000 cGy. The 5-year OSR of all the patients was 49%. Histological type (moderately differentiated squamous cell carcinoma) and patient age (> or = 55) were found to be significant prognostic factors for a worse OSR. Although survival decreased with increasing T stage, no significant difference was observed. The 5-year OSR of the patients treated with FAR therapy was 53% and was 51% with FAR therapy plus chemotherapy. Compared to FAR therapy alone, adjunctive chemotherapy did not increase OSR of the patients with NPC.

A clinical study was performed on 42 patients with parotid cancers initially treated in our hospital from 1972 to 1997. The five-year cumulative survival rate was 69% in the whole group and 72% in the radical surgical treatment group (n = 40). The five-year survival rates according to stage were as follows: stage I, 95% (21); stage II, 75% (4); stage III, 0% (1); and stage IV, 37% (16). The factors influencing prognosis were cases of T3 and T4 (p < 0.05), stage III and IV (p < 0.01), and cervical lymph node metastasis (p < 0.01). Regarding treatment modalities, a partial parotidectomy appeared to be a curable surgical procedure for T1 cases. However, a lobectomy is recommended for T2 cases. Furthermore our study proposed that prophylactic supraomohyoid neck dissection should be necessary for mucoepidermoid carcinoma (high-grade malignancy) and undifferentiated carcinoma of T4N0 cases.

Hypercalcemia and elevation of a serum PTH level (9800 pg/mL (normal: 160-520) were found in a 72-yr-old woman who had a lung cancer. She underwent pulmonary lobectomy for a suspected PTH-producing lung cancer. However, hypercalcemia and elevation of the serum PTH level were persistent postoperatively. Subsequent examination, using parathyroid scintiscanning, revealed a hot spot in the right lower part of the thyroid gland, suggesting hypercalcemia caused by a parathyroid tumor. She underwent bilateral exploration of the neck; however, four apparently normal parathyroid glands were seen. Therefore, hemithyroidectomy was performed for the possibility of an intrathyroidal parathyroid adenoma. Serum calcium and PTH levels declined after this operation. A nodular lesion was found in the cut sections of the resected specimen, which was consistent with the result of the scintiscanning. Histological examinations revealed a papillary adenocarcinoma of the thyroid gland, and the PTH-immunoreactivity in the tumor cells was confirmed. These findings strongly suggest that PTH could be produced ectopically by the papillary adenocarcinoma of the thyroid gland.

甲状腺癌に対して甲状腺亜全摘・全摘術を施行する場合に, 再発のない様に手術をすることは言うまでもない。それ以外に留意すべき点としては, 反回神経と上喉頭神経外枝及び上皮小体の処理であると思われる。本稿では, 上記の留意点を中心として手術手技を手術の各場面に分けて述べた。粘膜剥離子を多用することにより, 出血が少なく, 神経を損傷する危険性の低い手術が可能である。また, 前頸筋は腫瘍の浸潤がなければ出来る限り保存している。反回神経の同定を頭側で行う方法について述べた。これは, 大きな腫瘍が下極に存在したり, 気管傍転移の多発する症例や, 又, 反回しない反回神経症例の場合に有用と思われる。

Eighty previously untreated patients with hypopharyngeal carcinoma treated in our hospital from 1976 to 1990 were reviewed. The cumulative 5 year survival rate was 33%. Neck dissectin was performed on 31 patients who had nodal metastasis, and their cumulative 5 year survival rate was 25%. Our present principle of neck dissection for hypopharyngeal carcinoma with FAR therapy and neo-adjuvant chemotherapy based on our experience is as follows: 1. Neck dissection is performed only on the case with nodal metastasis. 2. Preoperative therapy of FAR therapy and neo-adjuvant chemotherapy is performed. 3. Accessary nerve and parotid gland without tumor invasion are preserved. 4. Neck dissection is performed even if nodal metastasis were disappeared after preopera tive therapy. 5. Internal jugular vein and sternocleidomastoid muscle are resected on neck dissection.

Radiotherapy thought vital in treating head and neck cancer, occasionally causes seriously local complications such as mandibular osteoradionecrosis (ORN). An analysis of mandibular ORN cases showed 16 in 638 subjects treated by radiotherapy, for an ORN rate of 2.5%. This rate was highest in subjects with oral cancer excluding the tongue, administered 81 Gy radiation dose, using X-ray plus electronic beams. 8 cases of ORN occurred within 1 year following radiation, and the 8 others within 5 years. Preservation treatment was successful in 44% of ORN cases, including surgery, for which the rate of final cure was 63%. With case of cancer recurrence, the rate was 25%. In 2 subjects dying of aspiration pneumonia, the cause should be a particular point for reflection. Radiotherapy involving mandibular bone should include special consideration related to the radiation source, radiation dose. Once ORN occurred, we should take care of the mixed cancer and dysphagia in the treatment.

To evaluate the efficacy and safety of weekly paclitaxel in patients with recurrent or metastatic head and neck cancer (HNC) by combined analysis of early and late phase II trials.Eligibility criteria included histologically proven HNC with recurrent or metastatic disease, measurable disease, PS 0-2, and one or no prior chemotherapy regimens. Treatment consisted of a 1-h infusion of paclitaxel at a dose of 100 mg/m(2) weekly for 6 weeks of a 7-week cycle. A total of 74 patients were enrolled: 37 between February and November 2004 in an early phase II trial and 37 between October 2005 and July 2006 in a late phase II trial.The median number of treatment cycles was two, and median dose intensity was 84.2 mg/m(2)/week. The most common grade 3-4 adverse events were leukopenia (37.5%), neutropenia (30.6%), anemia (12.5%), constipation (8.3%), peripheral neuropathy (5.6%), anorexia (5.6%), and pneumonitis (5.6%). Overall response rate was 29.0% according to RECIST. The median duration of response, median time to progression, and median survival time were 7.4, 3.4, and 14.3 months, respectively.This study demonstrates that weekly paclitaxel has promising activity with acceptable toxicity in the treatment of recurrent or metastatic HNC.

Cisplatin and infusional 5-fluorouracil were most commonly used as neoadjuvant chemotherapy or induction chemotherapy for squamous cell carcinoma of head and neck (SCCHN). But current analysis of neoadjuvant chemotherapy trials in head and neck cancer have not demonstrated a survival benefit for the use of induction therapy. Taxanes are an effective anti-cancer drug for SCCHN. New regimens including Taxanes as neoadjuvant chemotherapy for SCCHN are recommended.

The aim of this study was to evaluate the efficacy of intra-arterial infusion chemotherapy for head and neck cancers using a coaxial catheter technique: the superficial temporal artery (STA)-coaxial catheter method. Thirty-one patients (21 males and 10 females; 37-83 years of age) with squamous cell carcinoma of the head and neck (maxilla, 2; epipharynx, 4; mesopharynx, 8; oral floor, 4; tongue, 10; lower gingiva, 1; buccal mucosa, 2) were treated by intra-arterial infusion chemotherapy. Four patients were excluded from the tumor-response evaluation because of a previous operation or impossibility of treatment due to catheter trouble. Forty-eight sessions of catheterization were performed. A guiding catheter was inserted into the STA and a microcatheter was advanced into the tumor-feeding artery via the guiding catheter under angiographic guidance. When the location of the tumor or its feeding artery was uncertain on angiography, computed tomographic angiography was performed. The anticancer agent carboplatin (CBDCA) was continuously injected for 24 h through the microcatheter from a portable infusion pump attached to the patient's waist. The total administration dose was 300-1300 mg per body. External radiotherapy was administered during intra-arterial chemotherapy at a total dose of 21-70.5 Gy. The initial response was complete response in 15 patients, partial response in 7 patients, and no change in 5 patients; the overall response rate was 81.5% (22/27). Complication-related catheter maintenance was observed in 15 of 48 sessions of catheterization. Injury and dislocation of the microcatheter occurred 10 times in 7 patients. Catheter infection was observed three times in each of two patients, and catheter occlusion and vasculitis occurred in two patients. Intra-arterial infusion chemotherapy via the STA-coaxial catheter method could have potential as a favorable treatment for head and neck tumors.

To retrospectively evaluate the ultrasonographic (US), computed tomographic (CT), and magnetic resonance (MR) imaging features that differentiate traumatic neuroma from recurrent lymphadenopathy after neck dissection.Imaging findings of 10 patients with a traumatic neuroma and 17 with recurrent lymphadenopathy were reviewed. US and CT were performed in all patients; MR imaging was performed in 16 patients. Findings analyzed at US included the diameter of the long and short axes, the short-axis-to-long-axis ratio, and the presence of a central hyperechoic area. Findings analyzed at CT were contiguity with common or internal carotid artery, lesion location in correlation with carotid artery, and the presence of a hyperattenuating rim. Findings analyzed at MR imaging included signal intensity on T1- and T2-weighted images, the presence of ring enhancement, and the presence of a hypointense rim on T2-weighted images.Statistically significant differences were found between traumatic neuroma and recurrent lymphadenopathy in the short-axis-to-long-axis ratio (mean, 0.47 vs 0.72; P.001), the short-axis diameter (mean, 5.7 vs 12.2 mm; P.001), the presence of a central hyperechoic area (five of 10 patients [50%] vs one of 17 patients [6%]; P.05), the frequency of contact with carotid artery (two of 10 patients [20%] vs 13 of 17 patients [76%]; P.01), and the presence of a hypointense rim on T2-weighted MR images (three of six patients [50%] vs zero of 10 patients [0%]; P.05). Findings in other parameters were not statistically significant.Several imaging findings can differentiate traumatic neuroma from recurrent lymphadenopathy after neck dissection.

The conversion from a carcinomatous component to a sarcomatous one in spindle cell carcinoma (SPCC) of the upper aerodigestive tract is thought to occur via a series of molecular alterations; however the detailed mechanism is still unknown. We examined mutations at the H-ras and p53 genes in 16 SPCCs of upper aerodigestive tracts using PCR-RFLP, PCR-SSCP and direct sequencing analysis. The two distinct components, sarcomatous and carcinomatous components in SPCC, were analyzed independently. p53 mutations were detected in both components of SPCC (50.0%, 8/16), and those in the sarcomatous component were completely in accordance with those in the carcinomatous one. In contrast, H-ras mutations were detected only in the sarcomatous component (12.5%, 2/16), and not in the carcinomatous one (0%, 0/16). There was a statistically significant difference in prognosis between the patients with the H-ras mutation (n=2) and those without (n=14); the former had poorer prognosis (P=0.0049). Our results seem to suggest that the H-ras mutation is a relatively uncommon event in SPCC; however, the presence of H-ras mutations may be associated with a more malignant potential in SPCC, while actually occurring during the sarcomatous change itself.

The precise mechanism responsible for the frequent overexpression of cyclinD1 in human head and neck squamous cell carcinoma (HNSCC) is not known. In view of the fact that signal transducers and activators of transcription 3 (Stat3) is often activated in HNSCC cells, we examined the effects of Stat3 on cyclin D1 expression and cell proliferation in the YCU-H891 HNSCC cell line that displays constitutive activation of Stat3. Expression of a dominant negative Stat3 construct in YCU-H891 cells inhibited proliferation, cyclin D1 promoter activity, and cellular levels of cyclin D1 mRNA and protein. The levels of the antiapoptotic Bcl-2 and Bcl-X(L) proteins were also inhibited. In 51 primary tumor samples from patients with squamous cell carcinoma of the p.o. tongue, there was a significant correlation between increased levels of the activated form of Stat3, phosphorylated-Stat3, and increased levels of cyclin D1 (P0.0001). Increased tumor levels of phosphorylated-Stat3 were also associated with lower survival rates (P0.01). This study provides the first evidence that in HNSCC, constitutive activation of Stat3 plays a causative role in overexpression of cyclin D1, and in clinical studies, Stat3 activation may provide a novel prognostic factor. Furthermore, agents that target Stat3 may be useful in the treatment of HNSCC.

6004 Background: To establish the efficacy of adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) after curative treatment in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), we conducted a randomized phase III study to investigate whether S-1 is superior to UFT (uracil/tegafur). Methods: Patients with SCCHN who had received curative treatment and were confirmed to be tumor-free were randomly assigned to receive UFT (300 or 400 mg/day for 1 year) or S-1 (80, 100, or 120 mg/day for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were overall survival (OS), relapse-free survival (RFS), and safety. We estimated that 500 patients were needed to establish the primary end point. Results: From April 2006 through November 2008, a total of 526 patients (262 assigned to UFT; 264 assigned to S-1) were enrolled. The 3-year DFS rate was 66.0% in the UFT group and 64.1% in the S-1 group (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.66 to 1.16; [log-rank], P = .34). The 3-year OS rate was 75% in the UFT group and 82.9% in the S-1 group (HR, 0.64; 95% CI, 0.44 to 0.94; [log-rank], P = .022). The 3-year RFS rate was 63.6% in the UFT group and 68.2% in the S-1 group (HR, 0.81; 95% CI, 0.60 to 1.09; [log-rank], P = .16). There were no significant differences in 3-year DFS or RFS; however, the 3-year OS was significantly better in the S-1 group. The incidence of the following grade 3 or 4 events was significantly higher in the S-1 group: oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytopenia (5.0%). Conclusions: S-1 was not demonstrated to be superior to UFT in terms of 3-year DFS; however, 3-year OS was significantly better with S-1 than with UFT. Clinical trial information: NCT00336947.

The degradation of 125 I-labelled low-density lipoproteins (LDL) in HeLa cells was significantly inhibited when the cells were incubated either with the calcium channel blocking agents D600 and verapamil, or with the lysosomotropic agent chloroquine. However, nifedipine, another blocker of Ca 2+ channels, did not affect the degradation of 125 I-labelled LDL. The association of 125 I-labelled LDL with HeLa cells was increased in proportion to the concentration of D600, and 125 I-labelled LDL was accumulated in lysosomal fractions as assessed by Percoll density gradient analysis. Some 80% of 125 I-labelled LDL in lysosomes of HeLa cells treated with D600 was acid-insoluble. The rate of incorporation of [ 3 H]acetate into digitonin-precipitable material was increased 4-fold in the cells treated with 40 μg/ml D600 compared with untreated cells, but that of [ 3 H]mevalonate was not enhanced. About 8 h of preincubation of the cells with D600 or verapamil was required to inhibit the LDL degradation by 50% of the control activity. It was also found that the inhibitory action of D600 could be reversed by removal of D600 from the medium. The activities of lysosomal enzymes, cathepsin B, β-hexosaminidase, and acid phosphatase, were significantly decreased when the cells were treated with D600 and chloroquine, but not with nifedipine. Blockers of Ca 2+ channels which effect the activity of lysosomal enzymes, should be useful for the study of the lysosomal function.

Summary Chinese hamster V79 cell mutants resistant to compactin (ML236B), a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are defective in endocytosis of low-density lipoprotein (1). Two resistant clones, MF-2 and MF-3, differ in lipid composition from the parental V79 strain. In both the total cells and membrane fraction, the ratio of palmitoleic acid (16:1) / palmitic acid (16:0) is 0.4 – 0.5 in MF-2 and 1.7 – 1.8 in MF-3 while that in V79 is 0.2 – 0.3. By contrast, a hybrid clone between V79 and MF-3 shows a ratio of palmitoleic acid to palmitic acid very similar to that of V79. The synthesis of palmitoleic acid from acetate in the resistant clone is higher than in V79.

Two monensin-resistant clones show similar low-density lipoprotein binding activity but less internalization or degradation of low-density lipoprotein than the parental Balb/3T3 or other resistant clone. Sterol synthesis from radioactive acetate in the resistant mutant, MO-5, is inhibited by more than 70% of control in the presence of tenfold higher amounts of low-density lipoprotein than the dose that inhibits the parental Balb/3T3 to similar level. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity of Balb/3T3 and MO-5 is inhibited by 48% and 27% of control, respectively, in the presence of 10 micrograms/ml of low-density lipoprotein. Colloidal silica gradient centrifugation shows that transport of low-density lipoprotein from the surface membrane to the lysosome is much slower in MO-5 cells than in Balb/3T3 cells. Down regulation of low-density lipoprotein receptors on the cell surface in Balb/3T3 is observed by exposing the cells to 5-15 micrograms/ml low-density lipoprotein, whereas only slight if any down regulation is observed when MO-5 cells are treated with low-density lipoprotein. The altered endocytosis of low-density lipoprotein behaves as a dominant trait in hybrids of MO-5 and THO2-2, a derivative of Balb/3T3 resistant to both ouabain and 6-thioguanine.