A major impediment to cancer treatment is the development of anticancer drug resistance by the tumor. P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) are involved in multidrug resistance. Cepharanthin is a plant alkaloid that effectively reverses resistance to anticancer agents. It has been previously shown that cepharanthin is an effective agent for the reversal of resistance in P-gp-overexpressing cells. Cepharanthin has also been reported to have numerous pharmacological effects besides the inhibition of P-gp. It has also been found that cepharanthin enhanced sensitivity to anticancer drugs such as cisplatin (CDDP) and enhanced apoptosis induced by anticancer drugs. In the present study, we investigated whether treatment with cepharanthin improves the response to CDDP sensitivity in CDDP-resistant oral squamous cell carcinoma (OSCC) cell lines: H-1R and Sa-3R. The effect of cepharanthin on cell growth was investigated by the MTT method. In this study, we show that treatment of OSCC cell lines by CDDP in combination with cepharanthin resulted in a significant suppression of cell growth. Cepharanthin at 1.0 μg/ml, which was not cytotoxic when used alone, significantly increased the CDDP sensitivity of resistant cells, to a level similar to the parental cell level.
Cepharanthin might be used clinically as a reversing agent, and, combined with CDDP, it should be useful for treating patients with tumors.

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Squamous cell carcinoma (SCC) of the nasal vestibule is rare in head and neck malignancies. After resection of the carcinoma of the nasal vestibule, reconstruction surgery is often needed for a defect. The nose has several unique features in shape and function that make its reconstruction more complex. Reconstruction methods using auricular or costal cartilage as the framework, and paramedian forehead flap were reported. Here we report two cases of SCC of the nasal vestibule that underwent extensive nasal resection and reconstruction using composite free iliac bone for structural support, naso-labial flap for the floor of the nasal cavity, and free forearm flap for internal lining and skin coverage. Both cases had a good outcome aesthetically and functionally. We present the operation and procedure we used for the reconstruction, and compare the results with using a forehead flap.

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Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer.

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The use of dental implants in oral rehabilitation of head and neck cancer patients after ablative surgery and reconstruction has become a contemporary treatment modality in recent years. However, the treatment is sometimes difficult for the patients because it requires repeated surgical interventions and inconvenient local hard and soft tissue conditions, especially if the jaw was resected and reconstructed. We herein report on four patients who underwent dental rehabilitation with dental implants inserted simply in residual jaws. In these patients, chewing acceptability was markedly improved, and they were satisfied with the dental rehabilitation. The results of this study suggested that even a few implants inserted in residual jaws can markedly improve the QOL of patients who underwent jaw resection and reconstruction.

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Radioisotope (RI) methods, dye-staining methods, or both have been mainly performed for sentinel lymph node (SLN) mapping in oral cancer. However, it is very difficult to determine the true SLN when the distant nodes have been labeled or stained with these methods. In this study, computed tomographic (CT) lymphography with small volumes of iopamidol for detection of SLNs was performed in oral squamous cell carcinoma (N0). Here, SLNs could be detected when subsequent distant nodes are enhanced, since CT lymphography showed visualization of a direct connection between an SLN and its afferent lymphatic vessels draining from the injection sites and detailed anatomy of the lymphatic pathway.
At surgery, a blue dye-staining method was also performed. However, SLNs could be easily identified with the guidance of a skin surface marker and CT lymphography, whether they were stained or not. Thus, it is suggested that indrect CT lymphography may be useful for detection of SLNs in oral cancer.

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Despite many recent reports on oral function in glossectomized patients, there are few reports on postoperative oral function in partial glossectomy. The purpose of this study was to evaluate oral function in patients with partial glossectomy. Subjective and objective oral functions were examined in 39 patients with squamous cell carcinoma of the tongue. Their oral function was evaluated for speech, deglutition, mastication, and ingestion, with assessment by the patients themselves. Objective assessment was carried out on 100 Japanese syllable speech intelligibility and swallowing using 30ml of water. The results were as follows: 1. Subjectively, a few patients recognized their own difficulties in speech and swallowing function. 2. Objectively, all of the patients did not have large disorders. These results suggested that subjective and objective evaluations are needed in assessing patients with partial glossectomy.

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This study was done to evaluate the sensitivity and specificity of screening tests for aspiration in postoperative oral cancer patients. Ninety postoperative oral cancer patients were examined using the following tests: (1) repetitive saliva swallowing test (RSST); (2) modified water swallowing test (MWST); and (3) cervical auscultation. We used videofluorography to check for evidence of aspiration.
Results:
1. It was felt that RSST was better for 4/30 sec in postoperative oral cancer patients. The sensitivity and specificity of RSST in screening aspiration were 90.9% and 45.6%.
2. MWST and cervical auscultation showed similar results to those of patients with cerebrovascular disease. The sensitivity and specificity of MWST in screening aspiration were 81.8% and 91.2%. The sensitivity and specificity of cervical auscultation of the swallowing sound in screening aspiration were 54.5% and 96.5%. The sensitivity and specificity of cervical auscultation of the post-swallowing expiratory sound in screening aspiration were 90.9% and 86.0%.

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A phase I trial of concurrent TS-1 and radiation for oral squamous cell carcinoma was conducted to estimate the recommended dose schedule of TS-1. Patients received radiation in 2-Gy single daily fractions to a total dose of 40 Gy. Starting dose (level 1) was: TS-1 70 mg/m²/day administration 5 days per week. At least three patients were examined at each dose level. Step-up to the next level was performed when no patient showed dose-limiting toxicity. Dose-limiting toxicity was defined as grade 4 hematological toxicity and grade 3 or 4 nonhematological toxicity.
A total of 21 patients were enrolled in this study. The primary site was the tongue (6), floor of the mouth (4), upper gum (4), lower gum (5), and buccal mucosa (2). There were stage III in 11 patients, and stage IVA in 10 patients.
Two diseases achieved CR, and 17 diseases PR. The overall response rate was 90.5%. Histological evaluation after therapy according to Shimosato's classification showed grade I and IIa in one patient each, grade IIb in 8 patients, grade III in 9 patients, and grade IV in 2 patients.
Dose-limiting toxicity was not observed in this study. This method was safe and generally well-tolerated and demonstrated good efficacy in patients with locoregionally advanced oral cancer. An additional study has been initiated to determine the recommended dose schedule of TS-1.

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The objectives of the present study were to identify a salivary biomarker specific to oral cancer for noninvasive, convenient, repeatable and reproducible testing, and to apply this test in a clinical setting. Interleukins (IL-1β, -6, -8) were measured in saliva samples collected from 20 healthy individuals (15 men, 5 women; mean age, 32 years) and 19 patients with oral cancer (9 men, 10 women; mean age, 60.9 years). A sample of whole saliva was collected from each patient, and measured by ELISA. Levels of IL-6 interleukin were significantly higher for oral cancer patients. RNA tests were also conducted to identify salivary compounds that can serve as biomarkers. Using RT-PCR, three types of housekeeping genes were identified from whole saliva.
These data indicate that using saliva for a screening test for oral cancer and precancerous lesions was useful and prospective.

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We examined the therapeutic effect and adverse reaction for 31 oral squamous cell carcinoma patients who underwent neoadjuvant chemotherapy with TS-1 between April 2003 and March 2005. Among the 31 cases, 6 cases were complete response (CR), and 7 cases were partial response (PR). The response rate was 61.3% (19/31). Adverse reactions of higher than grade 1 were observed in 3 patients, and that of higher than grade 3 was observed in only one case. The response rates were: 75.0% for T1+T2 cases; 45.5% for T3+T4 cases. The response rate was 0% for multiple lymph node metastasis cases (pN2 cases) and postoperative distant metastasis cases. These results suggest that TS-1 is an effective therapeutic agent for oral cancer.

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It is well known that many hypopharyngeal cancer cases are double cancer. The esophagus, head and neck are the most common sites. Therefore, upper gastrointenstinal endoscopy has been done on esophagus or head and neck cancer patients, aiming to detect early-stage hypopharyngeal cancer. Recent development of the NBI (Narrow Band Imaging) endoscope has enabled us to detect early-stage cancerous lesions easily. This study examined ten lesions of six early-stage hypopharyngeal cancer cases, which were found with the NBI endoscope. Six of the lesions were pyriform sinus cancer, and three of them were unilateral, while the rest were bilateral. Posterior wall cancer was found in one lesion, though postcricoid cancer was not found. All of the cases were double cancer: esophagus cancer in four cases, oral cancer in three, oropharyngeal cancer in two, and gastric cancer in one. Tumors were removed perorally from patients under general anesthesia, and the healing process afterward has been good. Thus, it was found that by using the NBI endoscope, hypopharyngeal cancer can be detected during the cancer's early stage, making it easier to treat patients for a good prognosis.

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Introduction: The purpose of this study was to determine the efficacy of post-operative treatment in head and neck cancer patients with histological evidence of lymph node metastases.
Method: We treated 410 patients with squamous cell carcinoma of the mouth, mesopharynx and hypopharynx at the Department of Head and Neck Surgery of the Miyagi Cancer Center Hospital from May 1993 to April 2004. Among them, 143 patients of pathologically positive lymph nodes of the mouth, mesopharynx and hypopharynx received all of their treatment in the hospital.
Results: There were 59 patients with oral cancer, 25 patients with mesopharyngeal cancer and 59 patients with hypopharyngeal cancer. Pathologically, there were 40 patients of pN1 and 103 patients of pN2, and the number of nodal metastases was found to be from 1 to 18 (average 3.7 nodes) at the first treatment. Fifty-three patients underwent surgical treatment only, 10 patients received chemotherapy, 69 patients received radiotherapy alone and 11 patients received concurrent chemo-radiotherapy followed by surgery. Radiotherapy doses ranged from 44 to 50 Gy. The 5-year cause-specific survival rates for surgery alone, postoperative chemotherapy, postoperative radiotherapy and postoperative chemo-radiotherapy were 46.2%, 60%, 42.6% and 22.7%, respectively. There were no significant differences in the stastical analysis.
Conclusion: A significant increase in cause-specific survival rate was not observed in patients with post-operative radiotherapy because of lower total dose. It is recommended to raise the post-operative total radiation dose to 60Gy.

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Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor. Recently, it has been reported that SDC resembles ductal carcinoma (DC) in histology, and over-xpression of human epidermal growth factor receptor type-2 (HER-2) protein has been shown not only in DC but also SDC.
In this study, a patient with SDC of the right parotid gland receiving right total parotidectomy and elective neck dissection subsequently had skin metastases, and the tumor showed overexpression of HER-2 protein.
Trastuzumab is highly effective in DC, so we attempted to administer trastuzumab to this patient.

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The Japan Neck Dissection Study Group (JNDSG) receives support in the form of a Health and Labour Sciences Research Grant for Clinical Cancer Research from the Ministry of Health, Labour and Welfare, Japan, to conduct the “Study on Standardization of Surgery for Cervical Lymph Node Metastases of Head and Neck Cancer (H17-Gannrinshou-001).”
There are significant differences in the extent of resection of the cervical lymph nodes and non-lymphatic structures among neck dissections conducted in the large cancer centers in Japan.To eliminate these differences, the JNDSG has planned a multi-institutional prospective study, in which a surgeon of an institution visits another institution and observes neck dissection conducted by a surgeon of the visited institution, to complete our observation form composed of 79 detailed questions about the ongoing neck dissection.The observation forms will be collected and analyzed to extract questions when answers are significantly different among institutions and to initiate standardizing processes for surgical details concerning these questions.The standardizing processes include establishment of scientific evidence and, if scientific evidence is difficult to obtain, round-table discussions are held.The estimated number of enrolled patients is 235 in total.
Twenty-two institutions have participated in the study.During Feb. 18, 2004 and June 10, 2005, 106 patients were registered.According to the analysis of 74 patients, or 100 neck dissections, in the first step of the study, a significant difference among the institutions was observed for 16 surgical details, such as the upper resection line of the superior deep cervical nodes, the inferior resection line of the inferior deep cervical nodes, resection of the lymph nodes located postero-superiorly to the spinal accessory nerve, and resection of the sternocleidomastoid muscle.We will repeat the analysis of the observation forms to make the extracting process more precise and to make the standardizing processes more efficient.

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Bilateral lateral neck dissection in five patients was performed by the same surgeon to evaluate the significance of preservation of the cervical plexus in neck dissection. In these dissections, the sternocleidomastoid muscle and spinal accessory nerve were preserved in both sides, while the cervical plexus was not resected in the cervical metastasis negative side but was resected in the positive side (the side in which primary tumor extended more in the N0 case). The results of a questionnaire regarding the sense of the neck and shoulder, and the range of motion of shoulder abduction were almost normal in 2 of the 5 cases in the side of preservation of the cervical plexus more than one year after operation. Some symptoms regarding the sense of the neck and shoulder were seen in every case in the resection side of the cervical plexus. The results of a shoulder abduction test of bilateral shoulders more than one year after operation were normal in 4 of the 5 cases irrespective of whether the cervical plexus was preserved or not.
In conclusion, preservation of the cervical plexus may not necessarily cause problems regarding sense and motion following neck dissection. From now on, our policy will be to try to preserve the cervical plexus while considering the conditions such as the patient's build and cervical metastasis.

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Seventy patients, who were mainly considered contraindicated for surgery or who rejected radical surgery, received superselective intra-arterial infusion therapy of cisplatin (100-120mg/m²/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity, and conventional concomitant extrabeam radiotherapy.
The five-year progression-free rate of the primary lesion and overall survival were 82.1% and 54.4% for all patients, respectively. Acute toxic effects were considered acceptable; however, severe toxic events occurred in some cases, specifically cranial nerve palsy, MRSA pneumonia, sepsis, and osteoradionecrosis.
We confirmed high effectiveness of superselective arterial infusion and concomitant radiotherapy, which can concentrate attacks on locoregional diseases by decadose cisplatin. Moreover, even patients with unresectable diseases can be cured. There are various techniques and protocols for superselective arterial infusion, and they must be standardized. Moreover, indication for this treatment must be established.

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Superselective intra-arterial chemotherapy via the superficial temporal artery has become feasible for daily concurrent radiotherapy and chemotherapy for head and neck cancer. This novel method was used for oral cancer, and its efficacy was evaluated. Treatment consisted of superselective intra-arterial infusions (DOC total 60 mg/m², CDDP total 100 mg/m²) and concurrent radiotherapy (total 40 Gy) for four weeks as preoperative therapy. Thirty-four patients with stage III and IV oral cancer received surgery after this treatment, and pathological CR was obtained in 31 patients (91%). The possibility of organ preservation for advanced oral cancer was evaluated from this result. Patients with oral cancer stage III and IV were treated for four-week daily concurrent chemoradiotherapy, and the clinical response was evaluated after treatment. Clinical CR of primary sites was obtained in 15 patients, and the same treatment was continued one or two weeks. Thirteen patients (80%) were disease-free in the primary sites, and two (20%) relapsed. Two patients died of distant metastasis, and one died of local recurrence. This method can preserve organs and minimize functional disturbance, thus contributing to patient QOL.

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Superselective intraarterial chemotherapy for advanced head and neck cancers is a novel nonsurgical approach allowing organ preservation. There are two established methods for superselective catheterization: one transfemoral and the other retrograde catheterization through the superficial temporal artery (STA). The Seldinger technique using transfemoral catheterization may cause central nervous dysfunction and generally features a one-shot infusion procedure. However, selective catheterization through the STA does not cause neurologic problems, and intraarterial infusion can be repeated many times. After the percutaneous puncture of the STA in the supra-anterior region of the auricle, the guidewire is led selectively into the feeding artery of the tumor under fluoroscopic guidance, and then it is replaced with the infusion catheter. Recently, cisplatin (CDDP) has been recommended as a key drug for intraarterial chemotherapy, and weekly infusions of relatively low doses can be applied together with simultaneous intravenous sodium thiosulfate for systemic drug neutralization, or concurrent radiotherapy. This superselective intraarterial method is associated with a high response rate for primary carcinomas, only relatively mild systemic side effects, and acceptable common local toxicity. We consider that a combination of superselective intraarterial chemotherapy through the STA and concurrent radiotherapy has great potential for improving treatment results with organ preservation.

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