In 1960, Sato performed conservative surgery called tumor reduction in combination with intra-arterial infusion of anti-cancer drugs and radiotherapy to obtain satisfactory clinical results while minimizing facial deformation. We have used the Sato's method for maxillary cancer since the late 1960s, and achieved a five-year survival rate of 41.8% for the 78 patients treated between 1970 and 1980. In order to further improve treatment outcome, we incorporated imaging diagnosis using CT and MRI and switched to a method involving en bloc resection based on the effects of preoperative radiation therapy. As a result, a five-year survival rate of 62.1% and a five-year local control rate of 75.2% were obtained for the 136 patients who underwent en bloc resection between 1980 and 2008. Five-year survival rates by the T classification were as follows: T1 + T2, 88.9%; T3, 64.7%; T4a, 61.9%; and T4b, 38.5%. Rates for patients given preoperative arterial infusion and radiation therapy were as follows: T3, 82.0%; T4a, 73.4%; T4b, 50.0%. In terms of preoperative treatment, arterial infusion combined with radiation therapy was more effective than radiation therapy alone. We herein report outcomes at our department for en bloc resection for squamous cell carcinoma of maxillary sinus.

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In the management of the neck for early-stage tongue cancer, the wait-and-see policy is not recommended because of high occult cervical metastasis, which occurs in more than 20%, and poor survival rates.
Sentinel node (SN) biopsy has been used for deciding neck dissection for early-stage tongue cancer since 2000 in our department.
A series of 25 cases of stage I and II carcinoma of the tongue was analyzed prospectively. SN was detected in all 25 cases. In frozen pathological diagnosis, five cases were upstaged as a result of a positive sentinel node, of which neck dissection was performed in four cases. In 20 cases, there were no metastases in sentinel nodes.
Because two cases were staged as late T2, they underwent the pull-through method to manage the primary tumor, and then underwent neck dissection.
Eighteen cases were observed without neck dissection, of which 16 cases did not show evidence of metastasis. Although they were salvaged, post-operative submandible node metastasis (POSNM) occurred in two of 20 cases with negative SN. As a countermeasure to avoid POSNM, we use a lead plate to separate the cervical area from the injected oral area, and POSNM did not occur in 12 cases.
The sentinel node strategy provided a favorable outcome, as good as routinely performing neck dissection for early-stage tongue cancer.

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Sentinel node (SN) biopsy in the head and neck region has not been widely used in Japan, except at a few facilities. In order to elucidate the usefulness and drawbacks of this technique in head and neck cancer, 177 patients who had undergone SN biopsy at 7 facilities were retrospectively reviewed. As a result, frozen section analysis, particularly multislice sectioning, offers a relatively reliable intraoperative diagnostic method. We were able to perform immediate neck dissection based on the results of multislice sectioning as a single-stage procedure. T3 oral cancer had a significantly high false-negative rate compared with T1 and should not be indicated for SN biopsy. Patients identified as SN-negative by multislice section analysis had significantly better survival than SN-positive patients.

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According to many clinical practice guidelines, adjuvant chemoradiotherapy for postoperative high-risk patients with squamous cell carcinoma of the head and neck (SCCHN) is recommended as level 1 evidence.
However, in contrast to Western countries, adjuvant chemoradiotherapy for postoperative high-risk patients with SCCHN is not yet prevalent in Japan. The survival benefit of 3-weekly cisplatin at a dose of 100 mg/m² concurrent with radiation in a postoperative setting was shown in the EORTC 22931 trial and RTOG 95-01 trial, both of which were reported in the New England Journal of Medicine in 2004. Therefore, it is very important to analyze the safety and feasibility of this regimen and to encourage broad use of this treatment in the Japanese population.
This paper introduces the approaches to promoting adjuvant chemoradiotherapy for postoperative high-risk patients with SCCHN and the future prospects in this area in Japan.

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Immunotherapy with cancer-testis antigen is expected as a new therapy for cancer. We studied the expression of MAGE-A4 antigen in head and neck cancers, and planned a clinical trial with MAGE-A4 peptide. The expression of MAGE-A4 in head and neck cancer specimens in our department was observed in 29 of 75 (38.9%) by real-time PCR methods. Based on the results of our study, we planned a first-phase clinical trial of combined immunotherapy with MAGE-A4 peptide and cultured T lymphocyte for patients with head and neck squamous cell carcinoma. After standard chemotherapy (CDDP 70mg/m², 5FU 700mg/m² × 5 days), cultured peripheral T lymphocyte (1 × 10⁹ to 9 × 10⁹ cells/ml) and MAGE-A4 peptide bound to HLA-A*2402 by subcutaneous injection was administered. We treated a case of pharyngeal cancer safely without side effects related with MAGA-A4 peptide, and MRI showed the efficacy of the therapy. Spots of MAGE-A4 peptide-specific T lymphocyte were increased by ELISPOT after two cycles of peptide injection.

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A high prevalence of depressive disorder, between 15% and 50%, has been reported in head and neck cancer patients, although it is difficult to distinguish physical symptoms such as general fatigue, insomnia, and loss of appetite, which are common among cancer patients, from the psychiatric symptoms seen in depressive patients. Furthermore, co-occurrence of depression has been shown to be one of the risk factors of poor prognosis in cancer patients, partly because depressed patients are less likely to adhere to their medication regimen and modify their lifestyle appropriately. The efficacy of comprehensive psychiatric interventions (“liaison psychiatry”), including pharmacotherapy and psychotherapy, has been examined for head and neck cancer patients with co-occurrence of depression. Randomized controlled trials of psychiatric interventions for depression in head and neck cancer patients are needed to investigate the impact of such interventions on depression, quality of life, and mortality.

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Positron emission tomography (PET) can obtain functional information about tumors. There are some reports that intensity modulated radiation therapy (IMRT) planning was made using hypoxic imaging information obtained by PET. We used a semiconductor PET which was developed by the Department of Nuclear Medicine in Hokkaido University, where hypoxic imaging by [¹⁸F] fluoromisonidazole (FMISO) PET is available. We are investigating a dose escalation planning study of IMRT using FMISO PET imaging, and report on the usage of PET for radiotherapy in Hokkaido University.

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In cooperation with Chiba City Dental Association, we established an oral cancer screening program in 1992. In this article, we report the results of 20 years' experience and evaluate the effectiveness of oral cancer screening in oral cancer patients who presented to our clinic during this period. In the screening, member dentists of Chiba City Dental Association interviewed the subjects, and then carried out visual inspection and palpation. Suspected cases and those who required treatment were referred to secondary care institutions. The total number of subjects screened in the program was 3,429 over 20 years. Of the subjects who were referred to secondary care institutions, oral malignancy was diagnosed in 3 subjects (detection rate 0.09%). Treatment was instituted rapidly in all three cases, and all patients were discharged after surgery without any functional impairment. We divided the 20-year period into an early period (10 years from 1989 to 1998) and a late period (10 years from 1989 to 2008), and compared the patient characteristics between the two periods. The proportion of advanced stage cancer was smaller in the late compared to the early period, and the proportion of early stage cancer was greater in the late period. The 5-year survival rate was 78.1% in the early and 86.3% in the late period during the oral cancer screening program. Although the screening program may not be the only cause of these changes, the program is considered to be one factor that contributed to the changes in patient characteristics in the community.

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Concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion demonstrates good local control and overall survival rates due to the advantage of simultaneous infusion of anticancer agent with the synergistic effects of chemotherapy and radiotherapy. This study evaluated the therapeutic results, overall survival and local control rates in patients with advanced oral cancer treated with definitive concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion.
A total of 688 patients with carcinoma of the head and neck were referred to our institution between January 2001 and December 2006. Among them, 175 patients with carcinoma of the oral cavity underwent definitive concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m², cisplatin, total 125-150 mg/m²) and daily concurrent radiotherapy (total 50-60 Gy) for 5-6 weeks. Four weeks after the completion of all treatments, patients underwent biopsy of the primary lesion and radiological examinations. Complete response (CR) of the primary site was achieved in 160 (91.4%) of the 175 patients. Residual disease at the primary site was seen in 15 patients (8.6%), and 14 patients (8.0%) showed local recurrence during follow-up. Five-year survival and local control rates were 71.6% and 82.2%, respectively.

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We proposed transoral videolaryngoscopic surgery (TOVS) as a laryngeal preservation strategy for laryngo-pharyngeal cancer. By using a distending laryngoscope and rigid laryngeal endoscope, a large field of view and working space could be obtained which enabled us to resect tumors in en-bloc fashion. The indications for this surgery are oro-hypopharyngeal and supraglottic cancer in superficial, T1, T2 and selected T3 categories. TOVS can also be used for selected cases with recurrent tumor after radiation therapy. For resectable nodal metastasis, neck dissection can be performed simultaneously or 1-2 weeks later. In cases with more than a 1-year observation period (n = 42), 5-year crude survival, disease-specific survival, and laryngeal preservation rate were 74%, 85% and 89%, respectively.
A second advantage of TOVS is thorough evaluation of primary cancer lesion. Evaluation of tumor invasion depth is a promising way for optimizing the indication for neck dissection for clinically node negative cases.

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We performed a retrospective analysis of the association between tumor HPV status and the demographic and clinicopathological parameters of 83 patients with oropharyngeal squamous cell carcinoma at Hokkaido University Hospital, Japan, between 1998 and 2010. The parameters included age, gender, tumor subsite, Tumor-Node-Metastasis (TNM) stage, and overall survival. HPV status was established by multiplex polymerase chain reaction analysis.
Of the 83 oropharyngeal cancers, 22 were positive for HPV-16, two for HPV-18, and one for HPV-35 and HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumors (p = 0.0024) compared with HPV-negative tumors. Of the 51 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients (p = 0.0024).
HPV status is a significantly favorable prognostic factor in oropharyngeal cancer in Japan.

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The Japanese Cooperative Study Group for Basic Research in Head and Neck Cancer performed a multicenter prospective study to clarify the prevalence and genotype distribution of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (SCC) in Japan. Tumor tissues from 148 patients with newly diagnosed oropharyngeal SCC were tested for the presence of HPV genome by using polymerase chain reaction (PCR) and Hybrid Capture 2 (HC2). Non-cancerous palatine tonsils from 53 patients with tonsillectomy due to habitual tonsillitis or tonsillar hypertrophy were also examined as controls. High-risk HPV was detected in 76 (51.4%)of 148 tumor cases and none of 53 controls by PCR. HPV type distribution revealed HPV16 in 69 cases (90.8%), HPV18 and 58 in 2 cases each (2.6%), and HPV31, 35, and 56 in 1 case (1.3%) each. Compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among smokers and drinkers. In addition, detection of HPV using HC2 in oral brushing revealed that sensitivity and specificity were 90.7% and 97.1% respectively. This HC2 detection for HPV is considered to be effective and less invasive for patients with oropharyngeal SCC.

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Objective: To investigate therapeutic strategies for oropharyngeal squamous cell carcinoma based on an examination of clinical outcomes in our department.
Patients and methods: The patients were 99 cases with oropharyngeal squamous cell carcinoma treated in our hospital from March 2000 to March 2009. Five-year overall survival (OS) and 5-year cause-specific survival (CSS) were examined by the Kaplan-Meier survival curve. Subsite, stage, treatment (surgery group or radiotherapy or/and chemotherapy group) and prognosis were reviewed retrospectively.
Results: Five-year OS and 5-year CSS were 50% and 59%. Compared with the Stage I and II groups, the prognosis of Stage III and IV groups was significantly worse. As for the treatment, 5-year CSS of the surgery group was 76%, while that of the radiotherapy or/and chemotherapy group was 52%.
Regarding the subsite, 5-year CSS of the lateral wall type Stage I and II groups was 90% (surgery group: 100%, radiotherapy or/and chemotherapy group: 83%), and that of the Stage III and IV groups was 63% (surgery group: 87%, radiotherapy or/and chemotherapy group: 55%). Five-year CSS of the superior wall type Stage I and II groups was 85% (surgery group: 100%, radiotherapy or/and chemotherapy group: 66%), and that of the Stage III and IV groups was 50% (surgery group: 75%, 5-year CSS was not obtained in the radiotherapy or/and chemotherapy group).
Conclusion: The good outcome of the surgery group suggests that the indications for the operation were appropriate, and expansion of transoral resection should be considered in the near future. The outcomes of the radiotherapy or/and chemotherapy group require improvement.

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Surgical resection is the only salvage method for recurrent cancer at the base of the tongue after chemoradiotherapy. When widespread invasion of tumor to the larynx is observed, total laryngectomy is inevitable. However, if the tumor is localized, a glosso-valleculo-epiglottectomy (GVE) with preservation of the vocal cords might be feasible. It is generally recommended to reconstruct the defect after GVE with either primary closure or a small local flap (e.g. cervical apron flap). However, the reconstructed morphology of the supraglottic space is different from the original, and moreover excessive tension arises between tissues. As a result, it could cause frequent postoperative leakage, infection, aspiration pneumonia, placement of permanent tracheotomy, unnatural voice, and airway disorder. In view of these issues, we performed GVE and reconstructed the defect as follows, and obtained favorable functional results for phonation and swallowing in a patient with recurrent cancer at the base of the tongue. (1) The sensory and motor nerves of the pharynx: the superior laryngeal nerve and vagus were preserved. (2) The left half of the hyoid bone and the muscles attached to it were preserved. (3) Laryngeal suspension was achieved using the preserved thyroid cartilage and hyoid bone. (4) Using a relatively bulky rectus abdominis myocutaneous (RAMC) flap, we attempted to reconstruct the bulging curve of the base of the tongue. (5) To prevent transplant tissue atrophy of the RAMC flap in the long term, we anastomosed the cervical motor nerve and the intercostal nerve of the RAMC flap. Here, we describe the surgical techniques and the postoperative voice and swallowing function.

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The treatment results of 49 patients with hypopharyngeal carcinomas treated at our institute between 2000 and 2007 were analyzed. In general, concurrent chemoradiotherapy (CRT) with low doses of anti-cancer agents (low-dose CRT) was used as an initial treatment. Local tumor responses were evaluated after CRT with radiation doses of 40Gy. Patients whose local tumors showed a complete or almost complete response (CR) to 40Gy CRT subsequently received curative CRT with radiation doses of 70Gy. Patients whose local tumors did not show CR to 40Gy CRT underwent radical surgery for local tumors and cervical lymph nodes. The CR rates of local tumors to 40Gy CRT were 83% for 12 patients with T1 or 2N0 diseases, 67% for 15 patients with T1 or 2N1-3 diseases, and 32% for 22 patients with T3 or 4N0-3 diseases. The disease-specific 5-year survival rates and the larynx preservation rates were 81% and 67% for T1 or 2N0, 47% and 67% for T1 or 2N1-3, and 49% and 27% for T3 or 4N0-3, respectively. It is suggested that larynxes could be preserved in about 70% of the patients with T1 or T2 diseases by low-dose CRT whereas radical surgery or CRT with high doses of anti-cancer agents (high-dose CRT) might be necessary for about 30% of the patients with T1 or T2 diseases whose local tumors show poor response to CRT. High-dose CRT and/or neck dissection should be conducted as appropriate for patients with T1 or 2N1-3 diseases to improve their survival rates. Radical surgery is necessary for most of patients with T3 or 4N0-3 diseases. However, larynxes could be preserved by low-dose CRT for about 30% of patients with T3 or T4 diseases whose local tumors show high sensitivities to CRT. Moreover, intensive CRT such as high-dose CRT or CRT with selective intra-arterial infusion might improve larynx preservation rates for patients with T3 or T4 diseases. Multidisciplinary treatment based on the tumor response to 40Gy CRT is a treatment modality based on tumor sensitivity to CRT and is a useful method for the survival and larynx preservation of patients with hypopharyngeal carcinomas.

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Twenty-three patients (8 males, 15 females, age 40-88 years) with poorly differentiated thyroid carcinoma (PDTC) were treated at the Shikoku Cancer Center between 1999 and 2009. Of these PDTC patients, there were 15 cases of recurrent nerve invasion, 8 cases of tracheal invasion, 8 cases of esophageal invasion and 1 case of laryngeal invasion.
The 10-year overall survival rate was 52.4%, the 10-year cause-specific survival rate was 76.9%, and the 10-year disease-free survival rate was 58.3%.
The 10-year overall survival rate, the 10-year cause-specific survival rate and the 10-year disease-free survival rate of our 23 PDTC patients were statistically worse than those of 180 patients of papillary carcinoma of thyroid who were treated at our hospital during the same period.

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Because the Estlander-Abbe flap includes red and white lips, it is best suited to treating full-thickness lip defects. However, when the flap is used at the corner of the mouth, the corner becomes rounded, and as a result, secondary modifications are needed. If the upper lip is the donor site, Cupid's bow deformation is also an issue. We overcame these problems by the following measures:
1. A triangular flap was left in the upper red lip to prevent Cupid's bow deformation.
2. A small triangular flap was made in the red lip to serve as the lip commissure at the corner of the mouth.
3. The Abbe flap was made of two flaps, mucosal and dermal flaps, to make it easier to adjust the red lip volume.

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As nutrition support for head and neck cancer patients who receive chemoradiotherapy (CRT) and whose oral cavity or pharynx is exposed to radiation, we perform percutaneous endoscopic gastrostomy (PEG) tube placement. We examined 235 patients who underwent PEG in our division between January 2003 and December 2009. For 64% of them, the purpose of performing PEG was nutrition support for CRT, of whom 74% actually used the tube. However, the situation varied according to the primary sites of patients. Forty-four percent of laryngeal cancer patients who underwent PEG actually used the tube, which was a significantly lower rate than others. Also, 81% of them removed the PEG tube within one year. These findings suggest that PEG-tube placement for nutrition support is not indispensable for all CRT cases. Therefore, we recommend performing PEG for oral, oropharyngeal, and hypopharyngeal cancer patients.

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Pharyngocutaneous fistula (PCF) is one of the most troublesome postoperative complications after head and neck cancer surgery, such as total laryngectomy, and especially in patients with previous radiotherapy, it takes longer to be completely cured. Generally, PCF is treated with adequate drainage, neck compression and frequent dressings. When spontaneous closure is not achieved with these conservative treatments, surgical closure with free or local flap is needed.
In this report, we review two cases of postoperative PCF treated with Negative Pressure Wound Therapy (NPWT). NPWT is a relatively new method which is thought to promote healing of complicated wounds by utilizing topical negative pressure. Initially, there was concern that NPWT for PCF may promote salivary leak or air leak which would inhibit wound healing. However, in both of our cases, excellent wound healing was obtained and the fistula was successfully closed without surgical procedure. In addition to the effect of promoting healing, NPWT could save the time and effort of medical staff for performing frequent dressings.
We consider that NPWT is a useful option for the treatment of postoperative PCFs.

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