Fifty patients with advanced head and neck cancer (stage III or IV) at the age of 75 or older were treated surgically between 2002 and 2006. We investigated the medical complications and the problems of radical surgery in these elderly patients. The major complications and the ratio of each of them were as follows: hypertension 36%, heart disease 20%, central nervous system disease 14%, respiratory disease 16% and diabetes mellitus 12%. About half of them needed consultations with other medical specialists prior to surgery. The grade of preoperative performance status (PS) was 0 in 26 patients, 1 in 12 and 2 in 12. There were no patients with PS 3 or 4. The surgical procedures of them were almost the same as those of younger patients, e.g., reconstructive surgery in 30 patients including free flap in 20, free jejunum in 9 and pedicle flap in one. The frequency of postoperative complications and delirium was about 20% or lower, but it seemed difficult to prospect them preoperatively because no correlation was found between the surgical procedures and their frequency. We conclude that it is possible and reasonable for elderly patients to undergo radical surgery for advanced head and neck carcinomas, if they have good comprehension and the grade of their PS is 0, 1 or 2.

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Herein, we report the current treatment outcomes and measures for improving the QOL of 295 patients with hypopharyngeal squamous cell cancer treated at the Department of Head and Neck Oncology at the Cancer Institute Ariake Hospital during the five-year period between 1999 and 2003.
Among the 295 patients, 245 (83%) underwent radical treatment. Five-year cause-specific survival rates were as follows: stage I, 100%; II, 88.8%; III, 80.8%; IVa, 53.8%; IVb, 28.6%. Although satisfactory results were obtained up to stage III poor outcomes were observed for stage IV, which accounted for 67% of all patients. Metastasis primarily included distant metastasis (38%) and neck metastasis (25%). As postoperative treatment for improving outcome, the present department mainly provides radiotherapy and chemotherapy (CDDP, 5-FU or TS-1) for patients with ≥ 4 pathological metastases.
As measures for improving QOL, two-stage shunt formation using voice prosthesis (PROBOX2^®) was actively performed for post-laryngectomy voice restoration, and has produced favorable results.

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We analyzed 387 primary head and neck cancer patients with oral, laryngeal, mesopharyngeal or hypopharyngeal cancers in our hospital from 2002 to 2006 to study the diagnosis and treatment of multiple primary cancers. There were 23 multiple primary cancer patients out of 121 oral cancer patients including 3 synchronous cases, 19 metachronous cases, and 1 synchronous and metachronous case. There were 27 multiple primary cancer patients out of 130 laryngeal cancer patients including 5 synchronous cases, 20 metachronous cases, and 2 synchronous and metachronous cases. There were 19 multiple primary cancer patients out of 50 mesopharyngeal cancer patients including 6 synchronous cases, 12 metachronous cases, and 1 synchronous and metachronous case. There were 44 multiple primary cancer patients out of 86 hypopharyngeal cancer patients including 21 synchronous cases, 19 metachronous cases, and 4 synchronous and metachronous cases. Esophageal cancer was the most common second primary malignancy and gastric cancer was the second. Seventy to eighty % of the second primary cancers was expected to be detected by examination of the upper digestive system. Patients with oral cancer had head and neck cancers as second primary malignancies, whereas head and neck cancers as second primary malignancies were rare in the patients with laryngeal and hypopharyngeal carcinoma. Prognoses of the patients with second primary malignancies were significantly poorer than those of the patients without them. We report here the treatment strategy for the patients with head and neck cancer and second primary malignancies. It is important to consider the site, stage and degree of malignancy for the treatment of patients with head and neck cancer and synchronous second primary malignancy to determine the treatment methods and strategies.

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The zinc finger transcription factor, Snail, functions as a potent repressor of E-cadherin expression that can induce an epithelial-mesenchymal transition (EMT). Down-regulation of E-cadherin is thought to play a major role in the abnormal manifestation of EMT in epithelial-derived cancer types. Wnt signaling can also induce EMT and impact on multiple cell functions in neoplastic tissues. Although Wnt signaling could conceivably stabilize the pool of cytosolic β-catenin that is released from E-cadherin-bound sites as a consequence of Snail-mediated E-cadherin repression, direct interplay between the Wnt and Snail systems has remained a subject of conjecture. We demonstrate that Wnt-1 induces the up-regulation of endogenous levels of nuclear Snail protein as well as those of β-catenin, coupled with its ability to repress E-cadherin expression and support a tissue invasive EMT program. These data suggest that Wnt signaling stabilizes Snail and β-catenin proteins in tandem fashion so as to induce cancer invasion and metastasis via EMT program.

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Upper subtotal maxillectomy results in defects of the orbital floor, the maxillary anterior and lateral wall, and the nasal lateral wall with preservation of the palate. It also deforms the face with orbital dystopia, enophthalmos, diplopia, superio-posterior deviation of the alar base and the upper lip, and concavity of the cheeks. To treat this maxillary defect, an immediate reconstructive procedure with a free radial forearm osteocutaneous flap and titanium mesh plate is described in this article. The flap is harvested with linear skin flap (about 1.5cm in width) so that the donor site can be closed directly and thin radial bone (about 3mm in thickness) with precaution against pathologic fracture. The skin paddle is divided into two islands for coverage of the vascular pedicle in the maxillary sinus and obturation of the fistula between the upper oral vestibule and the nasal cavity. The radius is divided into two pieces, and made into an L-shape, one slat of which is for the naso-maxillary buttress, and the other is for the inferior orbital rim. The orbital floor is reconstructed with the titanium mesh plate and the plate remains exposed to the maxillary sinus. The flap is vascularized through the ipsilateral facial vessels.
Two patients underwent reconstruction by this method. The titanium mesh plate was not ued in one of them because of a high risk of recurrence at the orbital floor, which would have resulted in orbital dysfunction. Both of them were satisfied with their nose and lip remaining in the normal position.
A problem of this procedure is the volume for the cheek. Because the maxillary anterior wall is not reconstructed, the cheek after reconstruction becomes flat. But this procedure is easy, reliable, and with lower morbidity.

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Pharyngocutaneous fistula occasionally develops after total laryngectomy. Some fistulae are accompanied by wound infection and can affect the major cervical vessels. Because these complications are potentially life-threatening, prompt and appropriate treatment is required.
Pectoralis major myocutaneous (PMMC) flaps are often used to treat pharyngocutaneous fistulae. When the mucosal defect is small enough for direct closure, the muscular body of the PMMC flap is used to eliminate cervical dead space, and the skin island is used to cover the cervical skin defect. In some cases, the excess volume of the PMMC flap droops on the tracheal stoma and causes respiratory or esthetic problems and might need to be reduced through secondary surgery.
To solve such problems during surgical repair of pharyngocutaneous fistulae, we resect the skin paddle and fat tissue from the PMMC flap at the time of transfer. The resected skin paddle is used as a skin graft on top of the pectoralis major muscle. From 1997 through 2006, this method was used for 8 patients, including 7 men and 1 woman, with a mean age of 65 years.
With our resection method, flap drooping was eliminated and additional surgery became unnecessary. The appearance of the neck was also better than with our previous method. In addition, our resection method has several advantages. First, the flap donor site is smaller, and nipple resection is not needed. Second, the PMMC flap is safer when transferred as a muscle flap rather than as a myocutaneous flap. Our newly devised method for PMMC flap transfer is useful for salvage surgery when a pharyngocutaneous fistula develops.

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Since 1998, we have introduced the superselective intra-arterial chemotherapy method in order to decrease postoperation recurrences at the primary site for patients with carcinoma of the head and neck. Thirty-three patients with oropharyngeal carcinoma were treated with superselective intra-arterial chemotherapy. A catheter was inserted under fluoroscopic guidance via the right femoral artery (seldinger method). 80-100 mg/m² of CDDP was infused weekly. After completion of the CDDP infusion, sodium thiosulfate was simultaneously administered for systemic drug neutralization. Local control rates were 81.8% for all patients. The 5-year cause-specific survival rates were 69.1% for all patients, 72.0% for patients with base of tongue lesion, and 70.1% for patients with tonsillar lesion.
Our treatment policy for base of tongue lesion of oropharyngeal cancer was changed from surgery to intra-arterial chemotherapy. An important point in superselective intra-arterial chemotherapy is to appropriately select the feeding artery of the tumor.

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A retrospective study was performed to evaluate the efficacy of chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil (TPF) for squamous cell carcinoma of the pharynx. Primary tumor sites were epipharynx (5 cases), mesopharynx (11 cases) and hypopharynx (12 cases). Stage classifications were stage II in 6 cases, III in 5 cases and IV in 17 cases. They received 1-3 courses of chemotherapy of Docetaxel (80 mg day 1), Cisplatin (10-30 mg days 2-5), and 5-fluorouracil (500-1000 mg days 2-5), following radiotherapy for the patients with complete response. Local response rate was high at 90-100% (partial response + complete response). However, the response to neck node metastasis was not good and the remaining neck nodes were treated by salvage neck dissection in 10 cases. Larynx preservation after the present therapy was achieved in 6 patients with hypopharyngeal carcinoma.

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In this study, we present the treatment results of salvage surgery in 34 patients with residual primary tumor or local relapse tumor in the hypopharynx and cervical esophagus after radiotherapy (15 patients) or chemoradiotherapy (19 patients) at the Division of Head and Neck Surgery, National Cancer Center Hospital East between 1997 and 2006. All patients underwent total pharyngolaryngoesophagectomy (TPLE) as salvage surgery. Among these patients, postoperative complication was observed in 11 patients (32.4%). Fisher's exact test revealed no significant difference in postoperative complication rate between the RT group and CRT group. Tumors in the neck recurred in 10 patients (55.6%) after surgical resection. The tumor recurrence control rate for cervical lymph nodes was 84.7% for patients with clinically N0 disease after CRT who had not undergone neck dissection. The median survival time was 392 days.
We consider that salvage surgery can be safely performed by considering the necessity and method of operation, and the outcome of patients receiving CRT would be improved by salvage surgery.

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A retrospective evaluation of 71 patients with hypopharyngeal carcinoma in Akita University Hospital was carried out from 1991 to 2001. Actual disease-specific 5-year survival rate was compared between cases with primary surgical treatment and cases with radical concurrent chemoradiation. The disease-specific 5-year survival rate of 56 operation cases was 54%. When compared with stage of the tumor, 62.5% (8 cases) was found in stage I·II, and 45.5% (48 cases) in stage III·IV. On the other hand, only 42.7% (15 cases) was found in the radical concurrent chemoradiation group. Except for cases which are not suitable for statistical analysis due to small number belonging to stage I·II, 45.5% (13 cases) was found in stage III·IV. As a result, the disease-specific 5-year survival rate in operation cases was 11.3% better than that of radical concurrent chemoradiation cases. As for the stage III·IV groups, the number of operation cases was 6.9% higher than that of radical concurrent chemoradiation cases.
Curative multidisciplinary treatment dedicated for functional preservation requires close consideration in future.

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A total of 84 patients with untreated cervical esophageal carcinoma underwent resection in our hospital between 1984 and 2004. We reviewed clinical data on these 84 patients. Five-year overall survival rate by pathological stage was 50.3% for Stage II, 34.2% for Stage III and 32.7% for Stage IVa. The reason for poor prognosis of cervical esophageal carcinoma was that 77.4% of cases were Stage III or more. Head and neck doctors and esophageal endoscopic physicians need to perform positive medical examination of the border domain, and early detection is required if prognosis is to be improved. Lymph node metastasis is an important prognostic factor, as with other head and neck cancers. Primary lesion was not associated with prognosis. From examinations of lymph node metastasis, dissection of No.103 was considered unnecessary and a cervical approach appears sufficient for upper mediastinal dissection.

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The clinical features of 100 patients (82.0% benign, 18.0% malignant) with parotid gland tumors treated (operated, in principle) from January 2003 to December 2007 were retrospectively investigated. Approximately 85% of cases which were benign were pleomorphic adenoma (54.9%) and Warthin's tumor (30.5%). The pathological types of malignancy were various. If malignancies were accompanied by whole parotid gland tumors as one group, it accounted for 88% in these three groups. Moreover, by addition of basal cell adenomas to make it about 96% and based on the clinical findings and so on, mainly based on the diagnostic imaging, we created a preoperative (pathologically) diagnostic flow-chart. In the diagnostic imaging, MRI (contrast enhancement) and nuclear medicine inspection (99mTcO4, especially) were useful. However, 67Ga-citrate was not useful. Ultrasonic-guided FNA or needle biopsy (when absolutely necessary, within 2 weeks preoperatively) was additionally used for a patient which wavers about the operative indication and the one which needs preparation due to the choice of reconstruction method after resection and so on.

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Spinal accessory nerve palsy caused by the retractor during operation is often observed in the early postoperative period even in neck dissections in which the spinal accessory nerve was preserved. The range of active arm abduction, which is related to the trapezius muscle innervated by the accessory nerve, was measured to evaluate trapezius muscle paralysis and recovery.
Various degrees of paralysis were seen within 2 months postoperatively in 10 neck dissections in which the accessory nerve was preserved: it was less than 100 degrees in 4 cases of severe neck paralysis, 100-150 degrees in 3 cases of moderate neck paralysis, and more than 150 degrees in 3 cases of almost normal necks. It is considered that the various degrees of paralysis were caused by the different intraoperative damage to the spinal accessory nerve which was affected by the retractor and electric scalpel. Afterwards, the active arm abduction test results were almost recovered in all patients at around 6 months postoperatively.
In conclusion, the probability of temporary accessory nerve palsy is high even in neck dissections in which the accessory nerve was preserved. Appropriate physical rehabilitation according to the degree of spinal accessory nerve palsy is necessary to prevent adhesive capsulitis by trapezius muscle paralysis.

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A total of 827 head and neck squamous cell carcinoma (HNSCC) cases were treated at the Hyogo College of Medicine between 1986 and 2003. They consisted of 126 cases of the tongue, 59 cases of the oral cavity, 122 cases of the oropharynx, 174 cases of the hypopharynx, and 346 cases of the larynx. Of these, 38 cases (4.6%) were found to have other primary HNSCC, in which double cancers were 63.2%, and triple or more cancers were 36.8%.
The primary site of the first HNSCC was the hypopharynx 16/38 (42.1%), and it was the highest region of secondary or more HNSCC (9.2%). Heavy smokers with a Brinkman index of more than 601 were 62.2%, and heavy drinkers with alcohol intake of more than 31 g/day was 86.5%. Eighteen of 38 (47.4%) cases had multiple cancers in other areas, and 14 of 18 cases (77.8%) had esophageal cancer. In seven cases the treatment for second HNSCC was restricted as a consequence of the treatment of first HNSCC. The prognosis of allochronic multiple HNSCC was comparatively good, i.e., cases with no evidence due to disease were 62.5% and cases with death of disease were 20.8%.
About 40% of the allochronic multiple HNSCC were found more than 5 years after the first HNSCC was treated, and most of them were found with the appearance of subjective symptoms rather than by follow-up examination. In order to detect double or more cancers in the early stage after the treatment for the first HNSCC, it is important to inform patients about multiple HNSCC and to examine more frequently high-risk patients subject to heavy smoking and high alcohol intake.

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We reviewed outcomes of head and neck squamous cell carcinoma in 82 patients (69 males and 13 females) older than seventy in our hospital from April 2000 through March 2005. Laryngeal cancer was the most common cancer. Except laryngeal cancer, the number of advanced cases was larger than that of early cases. Other malignant tumor, hypertension, diabeties, and/or vascular disease were major past and concomitant illnesses of the patients. Nineteen cases were treated with treatment modalities less invasively changed from those planned for several reasons. In T3 and T4 cases, the post-treatment function for oral intake and prognosis were poor in oropharyngeal cancer, while surgical resection showed better control of locoregional tumors with good oral intake function in oral, laryngeal, and hypopharyngeal cancers.

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Objective: To evaluate preservation of organ function in the treatment of superselective intra-arterial chemoradiotherapy for advanced head and neck cancers.
Materials and Methods: Among 96 patients receiving concomitant radiation and intra-arterial docetaxel, systemic cisplatin and 5-FU chemotherapy, we identified laryngeal preservation rate, studied tracheostomy cases and gastrostomy cases, and evaluated videofluoroscopic examination and videoendoscopy.
Results: Laryngeal preservation rate of hypopharyngeal cancer is very high at 96.2%, and that of laryngeal cancer is high at 71.4%. Videofluoroscopic examination revealed improved swallowing function in 2 of 12, no change in 3, slightly worse in 5, and worse in 2 patients. Following treatment, the incidence of aspiration increased to 4 patients. Videoendoscopy revealed residual vallecula in a few cases. Only 7 patients (7.3%) required a tracheostomy and 4 patients (4.2%) required a gastrostomy. Most of the patients are able to swallow after chemoradiation.
Conclusions: Our new chemoradiation protocol is as good as other treatment modalities for maintaining organ preservation and function.

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