Gene therapy is thought to be one of the most promising treatments of malignant diseases. Gene therapy for cancers has been intensively investigated in recent years, and now the majority of these clinical trials are related to cancers. Gene therapy offers hope for cancer patients, especially those who are not cured by some therapies such as surgery, radiation, and chemotherapy. The targeted genes are categorized into two groups, 1) oncogenes and oncosuppressor genes such as p53 and E1A to directly kill tumors, and 2) immunoregulatory genes such as TAA, cytokines, and T-cell costimulatory molecules to enhance anti-tumor immunity. Vectors of the latter have been more actively developed, and many clinical trials are now being conducted around the world.
Until 2005, I was involved in the NCI translational research program, which had been conducted in the Laboratory of Tumor Immunology and Biology (LTIB), NCI/NIH, USA, for the purpose of developing cancer immunotherapy. LTIB developed novel recombinant poxviral vectors encoding transgenes for tumor-associated antigens (TAAs) and a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), designated as “TRICOM”. The preclinical studies using murine tumor models have demonstrated the anti-tumor efficacy of TRICOM vectors, in which TAA-specific T-cell immune responses could be enhanced followed by cure of mice, and the efficacy has been evaluated in many clinical trials. The preclinical findings upon a scientific basis are now being used to develop new strategies to achieve maximum anti-tumor immune responses, leading to the maximum clinical efficacies on a range of human cancers. This paper demonstrates the importance of logical preclinical studies for successful clinical trials and the possibility of cancer gene therapy targeting immuno-activation, through showing the combinatorial approaches of using several strategies with TRICOM.

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To evaluate the association between polymorphisms of alcohol-metabolizing enzymes and folate-metabolizing enzymes and the risk of oral cancer, we conducted a case-control study with 119 oral squamous cell carcinoma cases newly and histologically diagnosed and 357 age- and sex-matched non-cancer controls. Alcohol drinking showed a higher increased risk of oral cancer among population with the less active alcohol the dehydrogenase 1B (ADH1B) or aldehyde dehydrogenase 2 (ALDH2), compared with the subjects with active enzymes. In combination analysis of ADH1B and ALDH2 polymorphisms, we observed a synergistic increased risk in the heavy drinkers with less active ADH1B and ALDH2. Dietary folate intake was inversely associated with oral cancer risk. We found a non-significant decreased risk in MTHFR 677 TT genotypes. Examining the polymorphisms can allow us to identify the high-risk group in oral cancer susceptibility, thus such studies will produce useful information for oral cancer prevention.

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Inductive chemoradiotherapy has played an important role in preserving organs and functions in patients with oral squamous cell carcinoma (SCC). To determine whether a reduced form of surgery should be performed after chemoradiotherapy, accurate evaluation of residual tumor cells is essential. We investigated the clinical value of positron emission tomography with ¹⁸F labeled fluorodeoxyglucose (FDG-PET) in the management of oral SCCs. Forty-five patients underwent two FDG-PET studies, one prior to and one at 6 weeks after the chemoradiotherapy. Pretreatment FDG-PET was useful in predicting the response to treatment. Posttreatment FDG-PET could evaluate residual viable cells and prognosis. Organ preservation may be feasible based on PET evaluation. Hence FDG-PET is a valuable tool in the treatment of oral cancer.
¹¹C-Methionine (MET) is another promising tracer for PET that can be used to assess metabolic demand for amino acids in cancer cells. A MET-PET and FDG-PET study was performed during the same period to investigate diagnostic accuracy in 40 oral malignancies. Sensitivity and positive predictive value of MET-PET were 95% and 100%, respectively, and were comparable with those of FDG-PET. Further study is required to determine the diagnostic significance of MET-PET in evaluating response to chemoradiotherapy.

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Superselective intra-arterial chemotherapy via superficial temporal artery (HFT method) is feasible for daily concurrent radiotherapy and chemotherapy for oral cancer. The possibility of organ preservation in cases of advanced oral cancer was evaluated. Treatment consisted of superselective intra-arterial infusions (DOC total 60 mg/m², CDDP total 100 mg/m²) and concurrent radiotherapy (total 40Gy) for four weeks. Patients with T3 and T4 oral cancer were treated with four-week daily concurrent chemoradiotherapy, and the clinical response was evaluated after treatment. Clinical CR of primary sites was obtained in 23 patients, and the same treatment was continued for one or two weeks. Local recurrence was observed in four patients (17.4%), all of whom all patients underwent salvage operation, and the final local control rate was 95.6% (22 of 23 cases). One patient died of neck metastasis, and one died of local recurrence. One-year and 3-year survival rates were estimated by Kaplan-Meier's method to be 95.5% and 79.5%, respectively. In this treatment, it is important to identify the tumor's feeding artery and deliver a sufficient amount of anticancer drug to the tumor. Superselective intra-arterial chemotherapy for oral cancer has the advantage of delivering a high concentration of chemotherapeutic agents into the tumor bed with fewer systemic toxic effects than seen with systemic chemotherapy. Superselective intra-arterial chemotherapy using the HFT method can preserve organs and minimize functional disturbance, thus contributing to patients' QOL.

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Delayed neck metastasis and occult cervical lymph node metastasis are challengings issues in oral cancer. An earlier study showed that delayed neck metastasis of N0 oral tongue cancer represented a critical prognostic factor in survival. In this study, the risk of metastasis to level IV in patients with oral tongue cancer undergoing elective neck dissection was 5.3%. A previous study also showed that 15.8% of tongue cancers had either level III or IV nodes as the only manifestation of disease in the neck. To identify occult lymph node metastases, detection of micrometastases is essential. Sentinel lymph node biopsy (SLNB) in conjunction with serial tissue sections and immunohistochemistry provides high reliability and accuracy in the detection of micrometastases, supporting its usefulness as a staging tool in the future. A study in the Aichi Cancer Center reported that analysis of the three severest SLNs was sufficient to predict a patient's neck status. Moreover, in their clinical trial, frozen serial sections were useful for an intraoperative histopathologic diagnosis by SLNB to detect micrometastases. Reliable prediction of cervical lymph node metastases from a primary tumor biopsy sample would provide tremendous advantages for optimal treatment selection. However, the process of metastasis is a cascade of linked serial steps involving multiple host-tumor interaction. Metastatic cells therefore possess several properties to be able to perform all of these steps. The objective of our current study is to elucidate mechanisms in the early stages of metastasis. MMPs, which degrade extracellular matrix, play an important role in invasion and metastasis. We focus on MMP-2 and -9 because of their ability to cleave type IV collagen and investigate the role in invasion and migration of SCC cells. We also examine tissue microarrays from biopsy samples and investigate the relation to patient survival.

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Recently, the concept of regenerative medicine has been attracting much attention. Regenerative medicine utilizes cells, bioactive molecules and biodegradable scaffolds to regenerate lost tissues. Since the concept of regenerative medicine does not require donor tissue, it is considered as a novel and less invasive treatment for patients. At present, the applicable tissues and defect size are limited and the regeneration of larger tissue defects after tumor resection is not feasible. However, it is expected that at least a part of current reconstructive surgery will be replaced by regenerative medicine in the future. Currently, a clinical trial of bone regeneration using mesenchymal stem cells is underway in our facility. Other than bone, blood vessels and peripheral nerves are important target tissues for regenerative medicine. In this paper, the current research activities on those tissues are also discussed.

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The pathological majority of maxillary sinus cancers are squamous cell carcinomas (SCC). Patients with non-squamous cell carcinomas (NSCC) are rare. 105 patients who presented with maxillary sinus carcinoma between 1979 and 2006 were treated with combined therapy with surgery, radiotherapy, and regional chemotherapy. Among those, only 13 patients were diagnosed as NSCC. The 5-year and 10-year overall survival rates were both 78% with SCC patients. On the other hand, the 5-year and 10-year overall survival rates were both 59% with NSCC patients. The 5-year and 10-year local control rates were both 78% with SCC patients. On the other hand, the 5-year and 10-year local control rates were 51% and 41% with NSCC patients. There were significant differences in overall survival rates and local control rates among these groups. Especially, local control rates of patients with T4 NSCC showed poor results. Combined therapy with surgery, adiotherapy, and regional chemotherapy is an effective method for local control among SCC and non-advanced NSCC patients. However, performing combined therapy in patients with advanced NSCC disease must be considered carefully.

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Parotid gland carcinoma is characterized by various grades of malignancy related with many different types of histopathology. The ideal therapy for this carcinoma would include precise resection of the tumor based on histopathological diagnosis before and/or during surgery. However, in the current situation where fine needle biopsy cytology (FNA) and frozen section diagnosis (FS) as well as diagnostic imagings can not achieve high diagnostic rates, I have suggested utilization of FNA, FS, and postoperative radiotherapy as practical measures to eradicate the tumor and to increase the survival rates of the disease. En-bloc extirpation including the facial nerve is also chosen for those cases with preoperative facial nerve palsy, a notoriously poor prognostic factor. On the other hand, the facial nerve can be preserved for the patients without facial nerve palsy before surgery and tumor adhesion to the nerve during surgery. Further studies on the diagnosis and treatment may help improve the therapeutic outcome of parotid gland carcinoma such as high grade malignancies.

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Salivary gland carcinoma (SGC) is a relatively uncommon malignancy. In many articles only a few patients could be included and the data are insufficient to conclude that combination therapy is superior to single-agent therapy. There is no clear evidence to establish a recommended regimen as the standard treatment. To summarize previous reports, in single-agent therapy, objective responses were observed in 21/158 patients, 13% of adenoid cystic carcinoma (ACC), 9/36 patients, 25% of mucoepidermoid carcinoma (MEC), and 15/42 patients, 36% of adenocarcinoma (ADC). Cisplatin-anthracycline-5FU-based combination regimens also had activity in 36/127 patients, 28% of adenoid cystic carcinoma (ACC), 10/22 patients, 45% of mucoepidermoid carcinoma (MEC), and 19/39 patients, 49% of adenocarcinoma (ADC). Combination chemotherapy regimens have demonstrated higher response rates compared with single-agent therapy but there are no differences in the response duration, survival time and mean survival time (MST) among these two groups. In our study of concurrent chemoradiotherapy with CDDP/5FU, 17/19 patients, 89.5% were completed with the planned treatment. The response rate was 100% (10 cases of PR). 3-year overall survival rate and progression-free survival rate were 76.9% and 66.9%. In 10 cases of ACC, the mean disease-free time and survival time were 37.1 months (14.1-77.8) and 39.1 months (14.1-77.8). All patients of ACC were alive, including 2 patients with disease. Concurrent chemoradiotherapy can improve the overall survival rate of SGC.

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Between April 1997 and February 2006, 239 patients with malignant head and neck tumors were treated by carbon ion radiotherapy. The patients consisted of 130 males and 109 females aged from 16 to 79 years (average age 56.5 years). Histologically, the tumors were classified as follows: 85 with malignant mucosal melanomas, 70 with adenoid cystic carcinomas, 27 with adenocarcinomas, and 57 with other histological types of tumors. Although grade 3 acute reactions in normal tissues of skin and mucosa appeared in approximately 10% of the patients, the late reactions were grade 2 or less. Carbon ion radiotherapy can be therefore described as presenting no clinical problems.
Five-year local control by histological type was 75% for the malignant mucosal melanomas, 78% for the adenocarcinomas, and 67% for the adenoid cystic carcinomas. The therapeutic effectiveness of the carbon ion radiotherapy was particularly outstanding for locally advanced non-squamous cell carcinomas which make a tumor intractable to photon radiotherapy.

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Donor site morbidity from harvesting conventional flaps which have commonly been used cannot be overlooked. The authors prefer to use perforator flaps harvested from the anterior aspect of the thigh, which causes minimum donor site morbidity and facilitates simultaneous flap harvesting with the head and neck procedure. The authors studied 101 consecutive cases that underwent reconstruction using anterolateral and anteromedial thigh flaps between January 1995 and March 2005 at Okayama Saiseikai General Hospital. The utility and problems of these flaps along with a safe method of flap harvesting based on findings of anatomical variation are also described.

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Although perforator flaps have become popular for head and neck reconstruction, they have not been used for as many cases in our facility as we had expected, because conventional flaps surpass perforator flaps in some cases. We reviewed the postoperative complications of 603 cases with rectus abdominis myocutaneous flap (RAMCF) from 1986∼2006. Among them, 99.3% of cases succeeded in elevating flaps and 25.5% had surgical complications postoperatively. Twenty-seven flaps had pedicle thrombosis, but 6 of them (22.2%) were salvaged by secondary microvascular anastomosis, and the flap failure rate was 3.5%. The points of the reconstruction for head and neck cancer are discussed and the advantages of RAMCF are mentioned. Our methods of harvesting RAMCF are introduced.

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Hyperfractionated radiation therapy has been established as a radical treatment for head and neck cancer although the radiobiological hypothesis and its clinical implications are not new. The radiobiological hypothesis for hyperfractionation is derived from that of fractionated radiation therapy, and enables us to improve the therapeutic benefits by delivering a small fraction dose with optimal interfraction interval, i.e., 1) reduction of normal tissue complication while maintaining tumor control probability, and 2) improvement of tumor control probability while maintaining the incidence of normal tissue complications within an acceptable level. It is important to understand the radiobiological hypothesis or theory in the clinical application of hyperfractionation, and also necessary to predict or translate clinical outcomes including acute and late radiation morbidity especially after clinical trials such as combined hyperfractionation with concurrent chemotherapy.

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Altered fractionation schedules are based on two different concepts of radiobiology. One concept is that the radiation repair capability of cells in late responding tissues is higher than that of cells in acute responding tissues which include tumor tissues. Hyperfractionation utilizes this concept. The other concept is that accelerated repopulation of tumor cells occurs in a later period of radiation therapy. In order to overcome repopulation of tumor cells, the technique of accelerated hyperfractionation has been developed. Clinical results of altered fractionation schedules of radiation therapy could be predicted with the linear quadratic model thery for fractionated radiation. However, in the case of concomitant chemotheraoy and altered fractionation, it is difficult to predict its results with a simple radiobiology model. Randomized trias are required to examine the significance of chemoradiotherapy using altered fractionation.

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Radiotherapy for head and neck cancer (HNC) is very useful. If patients with HNC have been cured with radiotherapy, radiotherapy will have been highly beneficial to them. However, the prognosis of advanced HNC is poor. To improve the treatment results of advanced HNC, hyperfractionated radiotherapy and accelerated radiotherapy have been employed. Our institute has treated 117 cases (nasopharynx 5 cases, oropharynx 23 cases, hypopharynx 44 cases, larynx 45 cases) with HF since 1996. Local control rate and overall survival rate of all cases were 67.4% and 65.3% at 5 years, respectively. Compared with conventionally treated cases, our results with HF radiotherapy were better in hypopharyngeal cancers (local control p=0.0005, survival p=0.0023) and oropharyngeal cancers (local control p=0.0003).
Recent randomized trials and meta-analyses have demonstrated improved disease-free and/or overall survival rate by altering the schedule. Further trials with chemoradiotherapy in advanced HNC are needed to evaluate the effect and effective regimen.

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There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years. The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years). The effect was greater for the primary tumor than for nodal disease. The effect was also more pronounced in younger patients and in those with good performance status. Hyperfractionation seemed to yield a more consistent advantage for survival than accelerated fractionated radiotherapy. However, accelerated radiotherapy might be associated with higher non-cancer related death. We have to evaluate whether the benefit of hyperfractionated radiotherapy versus standard radiotherapy persists when combined with concomitant chemotherapy and the benefit of IMRT compared with altered fractionation.

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We report the 20-year experience of a single institution about accelerated hyperfractionation (AHF). We retrospectively analyzed the efficacy, and early and late toxicity associated with AHF in a series of patients with head and neck cancers. Between 1985 and 2002, 359 patients were treated with radical AHF. Primary sites were: larynx 237, nasopharynx 50, oropharynx 34, and hypopharynx 38. The AHF schedule was as follows: total dose 60-63 Gy, delivered in 40 fractions during 4 weeks. All cases were treated with twice-daily fractions. The 5-year actuarial loco-regional control rate was 98%, 85%, and 73% in stage I, II, and III-IV glottic laryngeal cancer, respectively. The 5-year actuarial loco-regional control rate was 80%, 69%, and 50% in stage I-II, III and IV oropharyngeal cancer, and 75%, 100%, and 40% in stage I-II, III and IV hypopharyngeal cancer, respectively. These data with AHF were superior to conventional radiotherapy. However, there was no therapeutic gain in nasopharyngeal cancer. Acute mucosal morbidity was significantly more frequent with AHF, but was transient and tolerable. Late complication rate was similar to conventional radiotherapy. AHF (60-62 Gy/40 fractionations/4 weeks) was a good fractionation regimen for head and neck cancers except for nasopharyngeal cancer.

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One huudred and seventeen elderly patients with advanced head and neck squamous cell carcinoma were treated at the Division of Head Neck Surgery, National Hospital Organization Kyushu Cancer Center between 2000 and 2006. Radical treatment was possible in 84% of the patients aged 65 to 75, and in 68% of those over 75. The 3-year relative survival rates were 78% and 75% respectively.

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Chemoradiotherapy plays an important role in the treatment of hypopharyngeal cancer. At Kyushu University, patients with hypopharyngeal cancer are initially treated with 30-40 Gy of irradiation with chemotherapy. The patients who demonstrate a good response continue to receive further radiotherapy. The other patients with poor response to radiotherapy receive surgery. In 44 patients with stage I-II hypopharyngeal cancer, 32 patients received chemoradiotherapy and 11 patients received surgery. There were no significant differences in 5-year disease-specific survival rates between the two groups (88.4% vs 90.9%). Local control with laryngeal voice preservation was achieved in 8 (88.9%) of 9 patients with stage I disease, and in 23 (67.6%) of 34 patients with stage II disease. In 175 patients with stage III-IV hypopharyngeal cancer, 90 patients were treated with chemotherapy, and 85 patients were treated by surgery after preoperative chemoradiotherapy. There were no significant differences in 5-year disease-specific survival rates between the two groups. However, 5-year local recurrence-free survival rates in radiotherapy group was 90.9% in T1, 59.7% in T2, 46.0% in T3, and 34.9% in T4. Patients with radiosensitive hypopharyngeal cancer seem to be curable with chemoradiotherapy, although local control rates should be improved.

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Concurrent chemoradiotherapy (CCR) plays an important role as one of the treatment choices for squamous cell carcinoma (SCC) of the head and neck, however, many problems such as patient selection and treatment method for cases with hypopharyngeal SCC have not been clarified yet. The good indication of CCR to SCC cases of the hypopharynx was examined based on the result of CCR in our department.

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We report an approach to the resection of oropharyngeal cancer with the following three important viewpoints in mind: 1) neck dissection approach, 2) approach to resection of primary tumor, and 3) how to divide the mandible. We must also consider salvage surgery as an option for high-risk cases which have already been treated with very high intensity chemotherapy or chemoradiotherapy. These cases must be treated very carefully because of the high risk of complications. Informed consent is very important when undertaking these operations. The safety and necessity of the surgery selected are paramount. Age, PS (performance status), and other factors have to be considered when selecting the operative approach. In the light of these above considerations, a safe and definitive resection of oropharyngeal cancer must be undertaken.

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It is important to reconstruct the tongue by adequate flaps to use remaining tissues with some functions for patients with tongue cancer. We present our device for tongue reconstruction in 110 cases. One of the keys to obtain good postoperative results is to reconstruct the tongue as a protuberant shape which helps the remaining oral function in articulation and swallowing.
In case of wide excision of the tongue we apply diaphragm reconstruction of the oral floor as well as tongue reconstruction by using a rectus abdominis musculocutaneous flap. Diaphragm reconstruction has two important meanings in functional reconstruction. One is to prevent postoperative decrease of intraoral volume of the flap and the other is to prevent misswallowing by pulling up the larynx. In the case of hemiglossectomy, a forearm or rectus abdominis musculocutaneous flap can be applied. In fatty patients a forearm flap is better and in slender patients a rectus abdominis flap is suitable. An elliptical-shaped design is usually adopted with partial deepithelialization of the flap, which is transferred to the base of the tongue. The long axis of the flap is about 15 cm with a width of 5 cm. After the flap is fixed, it is checked whether the tip of the reconstructive tongue has enough mobility.

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IMRT with non-uniform beams delivered by planned dynamic multi-leaf collimators can provide a better dose distribution within a target volume compared with conventional radiotherapy with uniform beams. The first step of treatment planning for IMRT is to acquire volumetric CT data by scanning the patients in the treatment position. Then, the clinical target volume (CTV) and the organ at risk (OAR) are outlined interactively on these CT images and a 0.5-cm margin is added around the CTV to define the planning target volume (PTV). Dose distribution of IMRT is calculated by using inverse-planning (IP). The parameters of beam weight optimization based on the inverse planning technique include some factors such as dose limits for each critical anatomical structure relative to the target volume and the penalty for exceeding the relative dose limit values in the regions of overlap. The optimum plan should be verified clinically and physically prior to the actual treatment of the patient.

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There are some OARs (organs at risk), such as the retina, optic nerves, optic chiasm, spinal cord, cochlea, and parotid glands in head and neck tumors. Usually the target is not geometrically well separated from OARs, and adding intensity modulation of the beam may be the only way to adequately treat the target while limiting the dose to surrounding OARs. IMRT enables us to deliver higher dose to the target while maintaining a low dose to OARs. It appears that patients treated with IMRT recover their salivary flow faster and more completely than those treated with conventional radiotherapy. IMRT is a good indication for nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus cancer, and cervical esophageal cancer. Usually, the dose distribution is quite inhomogeneous within the field from the high neck to upper mediastinum using the conventional radiotherapy technique. On the other hand, we can deliver a homogenenous dose distribution to this region with IMRT. IMRT is an effective treatment method for head and neck tumors.

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We introduced the clinical pathway to manage the post-operative care of supracricoid laryngectomy with Cricohyoidoepiglotto-pexy (SCL-CHEP). Before introducing the clinical pathway, all medical care including surgery, post-operative care, and swallowing rehabilitation, was managed within one admission. To improve the relatively long admission period (8 to 10 weeks), the medical care was subdivided into two admissions (1st admission: surgery + post-operative care and 2nd admission: swallowing rehabilitation). The clinical pathway was introduced to the 1st admission; the clinical data from the six patients were analyzed.
By introducing the clinical the pathway to a rather new treatment, in this case SCL-CHEP, complicated medical care was systematically understood and the problems elucidated, team care was reinforced among the different medical staff members, and the key factors for future revision of the updated pathway became evident.

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It is generally pointed out that the advantage of the clinical pathway is the useful progress schedule for a medical team approach as well as the opportunity for medical improvement by reviewing the pathway.
The clinical pathway of laryngopharyngoesophagectomy with free jejunum reconstruction in our hospital was improved twice to decrease the incidences (fall, self-withdrawal of the lines) related to post-operative delirium between November 2002 and June 2006. The improved clinical pathway, especially the decrease of ICU stay (from 2 days to 1 day) and reduction of bed rest, led not only to a decrease of delirium but also the elimiation of intravenous hyper-alimentation, earlier start of ingestion, and increase of patient's calorie intake on the day before discharge.
If a suitable clinical pathway according to each hospital's situation is introduced first, it may cause the medical improvement as a result that the clinical pathway should be reviewed to solve the problem that occurred afterwards by the whole medical team members.

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In recent years, many institutions have tried to introduce clinical pathways for the treatment of head and neck cancer. The main purposes are reducing health care costs, establishing a standard treatment and improving risk management by emphasizing evidence-based intervention and reducing variability in care. For the patient, this trial is acceptable for meeting their requirements for information disclosure. Until now, in the field of otorhinolaryngology, most of the clinical pathways have been used only for surgeries of benign tumors, laryngomicrosurgery, endoscopic endonasal sinus surgery, sudden deafness and facial paralysis. On the other hand, it has been considered that chemotherapy for head and neck cancer is easily given incorrectly, so the clinical pathway in this field is unpopular.
This time, we desiged, implemented, and studied the effectiveness of clinical pathways in chemotherapy for head and neck cancer. We report the merits and demerits of pathways in chemotherapy.

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Background: In an attempt to improve survival and keep organ function for cases with advanced head and neck carcinoma, recently concurrent chemoradiotherapy is widely used.
Objective: To evaluate complications of salvage surgery following organ preservation therapy.
Setting: University referral hospital.
Method: Six-year retrospective outcome analysis of 22 patients with resectable head and neck squamous cell carcinoma of the hypopharynx (15), mesopharynx (5), larynx (1) and tongue (1).
Results: The overall complication rate was 13/22 (59%). There were four major complications such as carotid rupture soon after wound infection. The operation time and total blood loss were clearly increased in salvage surgery compared to the control. Complications were greatly reduced by decreasing the area of neck dissection or using DP flap instead of injured cervical skin. Overall five-year survival rate of hypopharyngeal cancer with salvage operation was 50% in early cases and 30% in advanced cases.
Conclusion: Using DP flap and reducing the operation area (super-selective neck dissection) was effective to decrease the complication rate of salvage operation.

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Chemoradiotherapy (CCRT) is one of the standard treatments for advanced head and neck cancer patients. Radical neck dissection (RND) is one of the treatment options for residual neck. The procedure is difficult and it is required to consider carefully the indication of RND. Sixteen patients in 93 treated with CCRT under went RND. The internal jugular vein was preserved in 7 patients, sternocleidomastoid muscle was preserved in 5 patients, and accessory nerve was preserved in 5 patients. Mean operation time was 4 hours and 2 minutes, and mean blood loss was 258 ml. Five of in 9 patients are alive with functional larynx and pharynx. Major surgical complications were not observed in our series. The late complication of restriction of arm elevation was observed in 3 patients among 5 patients with functional larynx and pharynx. RND for residual neck after CCRT can be safely conducted and may contribute to the survival of eligible patients.

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Surgical complication rates of salvage laryngectomy after chemoradiotherapy (CRT) have been reported to be high. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed. Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital between 1990 and 2006 were divided into three groups according to preoperative treatments received: TL group (n = 35) without radiotherapy (RT) or CCRT, RT-TL group (n = 17) with RT alone, CRT-TL group (n = 34) with low-dose CCRT. Major wound complications were defined as major pharyngocutaneous fistulas which caused inpatient care for more than eight weeks or which were closed by surgery, bleeding that required surgical reintervention, and wound infection or skin necrosis that caused inpatient care for more than eight weeks. Minor complications were self-limited, managed with local wound care, and did not prolong inpatient care for more than eight weeks. We also analyzed wound complications of larynx preservation surgery after CCRT. Overall wound complications, both major and minor, were observed in 26% of the TL group, 35% of the RT-TL group, and 47% of the CRT-TL group. Major wound complications were observed in 11%, 18%, and 29%, respectively. A considerable but not statistically significant increase in the incidence of overall and major wound complications was observed between the TL and CRT-TL groups (p = 0.082 and 0.078, respectively). Pharyngocutaneous fistulas were the most common complication, occurring in 14/86 (16%) of patients. Patients who developed pharyngocutaneous fistulas after CCRT tended to require surgical reintervention and longer periods before the initiation of oral intake. Wound complications were observed in 2/3 (67%) of patients who had undergone larynx preservation surgery. High incidences of wound complications and poor wound recovery in patients undergoing salvage laryngectomy following CCRT should be taken into account before the initiation of CCRT.

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We clinically reviewed 214 patients with mesopharyngeal cancer who had been registered in the Niigata Prefecture Head and Neck Malignant Tumor Registration Committee during the past 14 years. The subregions included the lateral wall in 36.9% of the patients, anterior wall in 29.4%, superior wall in 18.7%, and posterior wall in 0.9%. The stage was evaluated as I, II, III, and IV in 6.1%, 19.4%, 23.3%, and 51.1% of the patients, respectively. The incidence of cervical metastasis was the highest (62.3%) in the patients with lateral wall lesions, followed by the patients with anterior, posterior, and superior wall lesions (58.1%, 50.0%, and 40.0%, respectively). In our subjects, the 5-year survival rate was 50.8%. In stage I, II, III, and IV patients, the 5-year survival rates were 75.0%, 71.8%, 50.2%, and 42.9%, respectively. There were significant differences in the 5-year survival rate between early and advanced cancer as well as between the presence and absence of cervical metastasis, suggesting the importance of early detection. There were no marked differences in the 5-year survival rate among the surgery, irradiation, and combination therapy groups consisting of patients without cervical metastasis. Among patients with cervical metastasis, the 5-year survival rate was higher in the surgery group, although there were no significant differences. However, in the surgery group, the primary disease-related mortality rate was significantly lower than those in the other two groups, suggesting the importance of surgical resection in advanced cancer patients.

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We analyzed 10 patients with oropharyngeal cancer and 17 patients with hypopharyngeal cancer who underwent Planned Neck Dissection (PND) after Concurrent Chemoradiotherapy (CCRT) from December 2001 to November 2005. Among patients with a positive surgical specimen, 22% had oropharyngeal cancer and 73% had hypoharyngeal cancer. The pathological status of positive neck specimens was honeycomb keratinized tissue at the center, and viable cancer cells in the peripheral zone. One of three previously clinically negative patients had a positive surgical specimen. It may be difficult to predict surgical outcome after CCRT.

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Treatment results of neck dissection with the preservation of cervical nerves for hypopharyngeal cancer were analyzed retrospectively by comparing neck dissection with the preservation of cervical nerves and that with the resection of cervical nerves.
Pharyngolaryngectomy or pharyngolaryngoesophagectomy with bilateral neck dissection was performed in 76 hypopharyngeal cancer cases between January 1992 and November 2001. Neck dissection with the resection of cervical nerves was performed on 42 sides of the neck in 21 cases (the cervical nerve-resected group). In 55 cases we attempted to employ neck dissection with the preservation of cervical nerves, but in 9 cases the cervical nerves were resected because of their nodal adhesion or involvement. Neck dissection with the preservation of cervical nerves was performed on 92 sides of the neck in 46 cases (the cervical nerve-preserved group). There were significant differences between background factors of two groups about age, sex, induction chemotherapy, preservation of accessory nerve, and pN classification. The 5-year cumulative control rates of cervical lymph nodes were 81.3% for the cervical nerve-resected group and 79.7% for the cervical nerve-preserved group. There was no significant difference between the two groups. It was suggested that neck dissection with the preservation of cervical nerves for cases whose cervical nerves were able to be preserved from metastatic lymph nodes under induction chemotherapy and post-operative irradiation was as effective to control cervical lymph nodes as neck dissection with the resection of cervical nerves.

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Recent advances in reconstructive surgery for the treatment of head and neck cancers have made it possible to radically resect the cancers. However, prognosis in hypopharyngeal cancer is poor and the choice of treatment is rather difficult. To better understand ways to improve the surgical management of hypopharyngeal cancer and to choose an appropriate treatment, we conducted a retrospective analysis of 54 patients who underwent surgery for hypopharyngeal cancer in our department in the past 8 years.
Twenty of the patients died. Neck metastases including retropharyngeal lymph node metastases and distant metastases were the main cause of death. Eight of these 14 patients had multiple neck metastases preoperatively, however, 5 of these patients were evaluated as N0. This result indicated that N-stage might not be a good indicator for the prognosis of disease. On the other hand, eleven of l4 the patients had multiple neck metastases in the pathological N-stage. Analyses of the numbers of patients with recurrence according to the pathological N-stage suggested that the pathological N-stage was a better indicator for the prognosis. Furthermore, the 5- year survival rate of patients with pN2c was worse than that with others.
These results indicate that accurate evaluation for neck metastasis is the most important predictive factor for the prognosis of hypopharyngeal cancer. The choice of treatment for cases with bilateral neck metastases might be reconsidered.

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A patient with metastatic carcinoma from a primary tumor of the salivary gland was successfully treated with concurrent chemotherapy (TPFL-Cepharanthine) and radiation therapy.
Two years 9 months after resection of a primary squamous cell carcinoma of the submandibular gland with radical neck dissection, a 68-year-old male was diagnosed with metastasis to the sternoclavicular joint region.
Concurrent chemo-radiotherapy treatments were conducted. Three courses of TPFL-Cepharanthine (TXT 40mg × 3, CDDP 100mg × 3, 5-FU 200mg × 3, Cepharanthine 50mg × 3) and 46 Gy, 23 fractions, radiation treatments were completed without severe adverse effects.
There has been no tumor recurrence or tumor marker elevation for 1 year 9 months post-treatment.
It is suggested that this chemoradiotherapy is effective for the treatment of primary salivary gland squamous cell carcinoma.

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The average life span of the Japanese is long and therapy for advanced aged cancer is done so often. However, how old is “advanced age” of each cancer? The high-risk cancer rate is higher in advanced aged thyroid cancer compared with that in low aged cancer. We defined advanced aged thyroid cancer by evaluating 251 cases operated in our department. The high-risk cancer rate was higher in the group of over 75 years old compared with the group of under 75 years old. Furthermore, in the group of over 75 years old, the rate of Ex2, anaplastic cancer, and distant metastasis was higher compared with the group of under 75 years old. From the rate of high-risk cancer, advanced aged thyroid cancer was defined as the cases of over 75 years old.

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A low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor, originally described by Evans in 1987.
We experienced a 73-year-old male who presented with a mass in his left deep neck. As a treatment, the mass was surgically removed and it was diagnosed as a low-grade fibromyxoid sarcoma (LGFMS), a very rare tumor.
LGFMS is not only a rare sarcoma, but also shows a high rate of local recurrence and distant metastasis.
Additional radiotherapy was performed because of a positive surgical margin. The postoperative course of the patient has been uneventful without any recurrence or metastasis.

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The non-circumferential hypopharyngeal defect following partial hypopharyngectomy has often been reconstructed either with a free jejunal patch graft or forearm flap. Conventionally, free jejunal patch graft was transferred in an isoperistaltic fashion, but pool of diet was occasionally seen due to the peristaltic constriction and circular folds of the jejunum. To overcome the disadvantage, we recently transferred the jejunal patch in a 90-degree transposed fashion. Functional results of the study group (new method, n = 8) were compared with those of the control group (conventional method, n = 7). The validity of the new method was assessed based on the time required for initiation of oral intake and postoperative swallowing function. On the first video-fluorographic study, pool of contrast medium was observed in no patient of the study group but was observed in 5 of 7 patients of the control group. The patients in the study group began to have oral intake 8 days earlier on average than patients in the control group. As a result, all 8 patients achieved adequate oral intake with rare dysphagia or regurgitation in the study group while in the control group 5 of 7 patients had dysphagia or regurgitation to some extent. Our modified procedure provides safer hypopharyngeal reconstruction with stable swallowing function, overcoming the disadvantage of the conventional jejunal patch graft, and can be applied for non-circumferential hypopharyngeal defects so long as the patient's general condition permits a jejunal segment to be harvested.

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The accuracy of panoramic radiography for diagnosing the depth of bone invasion by squamous cell carcinoma of the mandibular gingiva was assessed by comparing the radiological depth (D_x-ray) and the histological depth (D_Histol) of bone involvement. D_x-ray was consistent with D_Histol in most tumors showing the oppressive type of histological intraosseous invasion. On the other hand, tumors of the infiltrative type had a tendency of underestimation in D_x-ray compared to D_Histol. Those data suggest that the intraosseous invasion pattern could predict the magnitude of difference between D_x-ray and D_Histol. The present study, however, failed to identify predictive factors for the intraosseous invasion pattern preoperatively.

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It is how possible to perform precise intensity-modulated radiation therapy (IMRT) thanks to modern radiation apparatus and innovation of computer technology. However, it needs very time-consuming procedures such as difficult treatment planning, examination of complex beam data, precise registration before treatment, and beam delivery of multiple various beams with intensity-modulated beams. Helical tomotherapy is designed to deliver intensie IMRT with several sophisticated techniques, and the machine reduces the time and procedures required to prepare and deliver IMRT. In Aichi Cancer Center Hospital, helical tomotherapy was used to deliver IMRT for patients with head and neck cancer from June 2006. We report here our clinical experience of 56 cases head and neck cancer treated with helical tomotherapy in our first year.

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Many methods have been reported for mandibular reconstruction after ablative tumor surgery. Particulate cancellous bone and marrow (PCBM) combined with platelet rich plasma (PRP) and a titanium tray make it easy to reshape the contour of the mandible. Recently, this method has been advancing, because of the ability to harvest PCBM from the posterior ilium and the use of PRP.
Reconstruction following ablation of two malignant and five benign tumors was performed with this method in our hospital. Sufficient PCBM was harvested from the posterior ilium and postoperative complications were very few. Infection did not occur even with an intra-oral approach. We inserted osseointegrated implants in three cases.
We believe that this method has many advantages.

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We have begun to apply arterial redistribution and preoperative embolization in superselective intra-arterial chemotherapy from the superficial temporal artery. This study examines two typical cases of upper gingival cancer.
Case 1 was a male, age 61, with T4N0M0 upper gingival cancer. Drug dosage began with 50∼100 mg/m²/day of 5-FU, while 15 mg/m²/hour of Docetaxel was also given once a week for three weeks. At the same time, radiation therapy with a total of 30 Gy (2 Gy at a time) was given. Immediately before the operation, embolization in the internal maxillary artery was performed in order to limit bleeding. Case 2 was a female, age 73, with T3N0M0 upper gingival cancer. This patient was also given 5-FU and Docetaxel for four weeks respectively with a total of 40 Gy radiation therapy. No operation was performed. Both cases gained CR with a sole side effect of grade 3 mucositis.
Superselective intra-arterial chemotherapy with arterial redistribution in the oral area is highly effective due to local, concentrated dosage of anticancer drug and reduced side effects. It is a promising method to replace surgical operation especially in cases of upper gingival cancer, whose tumor is often limited to the internal maxillary artery alone.

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