Between 1978 and 1993 we experienced 143 mediastinal surgery for the head and neck cancer. Indications for this surgery include 1) tumor extension to the mediastinum, 2) presence of mediastinal metastasis, 3) postoperative tracheal necrosis, 4) stomal recurrence, 5) postoperative esophageal stenosis and fistulas. the extent of mediastinal dissection was to the level of the carina and tumors extending to the pleura or vessels were not necessarily contraindicated in selected patients. The maximam tracheal resection was 1.5cm from the carina.
The most significant problem of mediastinal surgery is postoperative complications around the tracheostoma in post-laryngectomy patients which easily resulting in fatal innominate artery hemorrhage. In our series we have experienced 4 postoperative innominate artery hemorrhage and two patients died because of it. To prevent these complications careful attention must be paid to the following points, to avoid undue tension at the tracheal cutaneous suture line, to keep sufficient blood supply to the tracheal stump, to protect major arteries using some type of the muscule flap if necessary. In case of the short trachea We usually resect the sternum, the clavicular head and the ribs as wide as necessary, and rotate a myocutaneous or muscle flap such as pectoralis maior, latissimus dorsi, rectus abdominal etc, to insert between the trachea and the innominate artery to prevent tracheo-innominate fistulas. And then in case of extremely short trachea we use the free radial forearm flap on it for resurfacing of mediastinum. The 5-year survival is as follows; thyroid 47.1%, hypopharynx 38.7%, cervical esophagus 30.6%, larynx 21.4%, stomal recurrence 15.2%.

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From 1962 through 1993 the mediastinal operations were performed in 63 cases: thirty cases of pharyngoesophagial carcinoma, eighteen cases of thyroid tumors, four cases of stormal recurrence, three cases of parathyroidoma, three cases of thymic carcinoma, two recurrence cases of laryngeal carcinoma, tracheal carcinoma, and one case of metastatic carcinoma to the thoratic wall from the kidny.
The prognosis of malignant cases but tyroid carcinomas was poor, but it seemed meaningful that such patients were save from the air way obstruction and became possible to take foods through the mouth even if it was short term.

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The rates of lymph node metastases in the upper mediastinum for carcinoma of the larynx, hypopharynx and cervical esophagus were 5.1%, 17.0% and 75.0%, respec tively. In the hypopharyngeal carcinoma, the rate for the lesions extended to the cervical esophagus was higher than that for those not extended (42.9% vs 10.6%).
Our principal approach for upper medias tinal dissection (UMD) has been through the neck without sternal manubrectomy, except for the case of apparent preoperative upper mediastinal metastases or lower tracheal stump which necessitates mediastinal tracheostomy. There was no recurrence in the upper mediastinum in the patients with hypopharyngeal carcinoma extended to the cervical esophagus who underwent UMD without sternal manuhrectomy, compaired with 58.3% in the patients who underwent no UMD. From this result, the usefulness of this procedure was suggested.
Nine cases were reported who underwent laryngopharyngoesophagectomy, UMD with sternal manuarectomy and mediastinal tracheostomy. In four of the nine cases a pectoralis major myocutaneous flap was used to construct a tracheal stoma. Both pectoralis major muscle flap and local skin flap were used in two cases, local skin flap only in the remaining three. The trachea was relocated to the right side of the right brachiocephalic artery in four cases. Two operative deaths occurred.
One died of bleeding from the brachioce phalic vein at the eighth day postoperatively after disruption of a tracheocutaneous suture line. The other died of MRSA pneumonia with tracheal necrosis at the 42th day. Up to now, only two has been alive for 13 and 24 months.

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The concept of mediastinal dissection differs much from the conventional radical neck dissection mainly for the singularity of the mediastinal lymphatic flow. The access to the upper mediastinum is critical to get enough operative field. We developed a new approach to the upper mediastinum using curretage of the upper part of the sternal manubrium together with half of the clavicle. The inverted T incision at the third intercostal level is also available for less invasive mediastinal dissection. The highpoints of mediastinal dissection are, to perform thorough dissection of the upper thoracic paraesophageal lymph nodes (No. 105) and the thoracic paratracheal lymph nodes (No. 106) preserving the vascular network around the trachea and the innominate artery, and to be ready for the reconstruction of the trachea or the recurrent laryngeal nerve for better prognosis. A reduction surgery, however, should be considered when the patient is complicated with severe diabetes mellitus or liver cirrhosis.

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Twenty two patients of advanced head and neck cancer underwent mediastinal dissection at our institution between 1981 and 1993. There were eleven men and eleven women, ranging in age from 42 to 82 years (average: 60.5). Ten patients had extended thyroid cancers, three laryngeal cancers, two hypophryngeal cancers, two cervical esophageal cancers, two mediastinal lymphnode metastases of which origins were unknown and other three mediastinal lymphnode metastases of which origins were nasopharyngeal cancer, cancer of the parotid gland and cancer of the colon respectively. The postoperative complications occurred in six (27%) of twenty two patients. These complications were three vascular catastrophe (caused by mediastinitis and necrosis of the trachea), two pneumonias and a necrosis of the trachea which was rescued by immediate debridement. Five year survival was 45% in thyroid cancers (papillary cancer 75%, anaplastic cancer: 0%) and 31% in other cancers.

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Reconstruction of recurrent nerve palsy is two methods, one is static, the other is dynamic.
Static methods are mediofixation of vocal cord, silicone injection, etc. Dynamic methods are nerve reconstruction, transplantion of nerve-muscle complex. But, dynamic methods are rare of recovery from paresis. In operating time of thyroid cancer or esophageal cancer, immediate anastomosis of cut end is easy and expected recovery from paresis. In addition to end-to-end anastomosis, anastomosis with cervical vagal nerve is available for cut in thoracic space.

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Recent advances in plastic & reconstructive surgery have dramatically improved the result of head and neck reconstruction. In order to meet the growing need for the three-dimensional, anatomical reconstruction, a reliable flap with multiple skin paddles and multiple bone segments has been searched for. We believe that the subscapular system composite flap is best suited for this purpose. The latissimus dorsi (LD) mc flap and scapular flap can be used as a main flap. The lateral border and inferior angle of the scapula can be elevated as one or separate bone flaps. We have also developed pedicled rib bone flaps vascularized with perforating branchs of the 8th-11th posterior intercostal arteries which can be attatched to the LD mc flap. It should be atressed that all these bone flaps are well vascularlized and can be arbitrarily and three-dimensionally positioned. The LD muscle can be splitted and used for dynamic reconstruction (smile restoration). Thus with the only one pair of long and reliable vessels a versatile and “multifunction” flap can be elevated and tailored to fit each patient's unique defects. We also found that the angular branch is better used with the LD mc flap than with the scapular flap because it gives longer pedicle.
Thirteen maxillary reconstruction and 9 mandibular reconstruction was done with good and predictable result and with very low rate of complication. Our operative technique and representative case is shown.

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Large massive defects of the head and neck regions following resection of the advanced or recurrent carcinoma often consist of losses of bone and muscle as well as skin. These massive composite defects have been reconstructed with a few large composite tissue transfers. With these transplants, the cosmetic and functional results are limited because (1) they lack volume, (2) the components of the flaps cannot be separated, (3) the pedicle vessels are too short, and (4) the donor sites are close to the head and neck.
Combined “chimeric” composite flaps with microanastomoses consist of two or more flaps or tissues, each with an isolated pedicle and a single vascular source. Based on 32 patients, a combined anterolateral thigh flap and vascularized iliac bone graft based on the lataral circumflex femoral system and the deep circumflex iliac system was the most commonly used combination. An anteromedial thigh flap and a paraumbilical perforator-based flap were also combined with this principal combination. The advantages of this flap are: (1) The flap is relatively thin and pedicle vessels are up to 10cm longer for harvesting of the flap and larger than those of other flaps. (2) It is unnecessary to reposition the patient. (3) The vascular pedicle to the skin can be separated from that of the bone. (4) The donor site is not close to the recipient site. (5) The donor scar is in an unexposed area. (6) The skin territory of this flap is extremely wide. (7) A combined anterolateral and anteromedial thigh flap and vascularized iliac bone graft can be easily obtained as an extended combined osteocutaneous flap. (8) Other neiboring skin flaps such as a groin flap, a paraumbilical perforato-based flap or a medial thigh flap can be combined with this flap because several major muscle branches to be anastomosed derive from the lateral circumflex femoral system. This composite flaps are considered suitable for the repair of large massive composite defects of the head and neck.

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Free vascularized scapular osteocutaneous flaps were used in 26 consecutive cases of mandibular reconstruction following tumor surgery. Our operative procedure is presented. Subscapular vessels that derive from axillary vessels are dissected for the vascular pedicle. Subscapular artery bifurcates into cicumflex scapular and thoracodorsal arteries. Bone flap can be made bipedicled, one is osteal branch from circumflex scapular artery and the other is angular branch from thoracodorsal artery. That makes it safer to do the osteotomy within the bone flap to mimic the anterior curvature of mandible. Thin and malleable miniplates were successfully used to fix the bone in our cases. Good bone union was obtained at the sites of osteotomy and at the connection between bone graft and mandible remnants as well. After the durable mandible was accomplished, dental reconstruction was carried out by implanting the artificial dental root into the grafted scapular bone in 8 cases. The dental implantation into the reconstructed mandible was done in a similar manner as into the normal mandible, in outpatient base of dentistry. We experienced 4 patients who have been able to masticate ordinary foods for more than 5 years. This fact means the scapular osteocutaneous flap is the method of choice to create a sound mandible not only cosmetically but also functionally.

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In a mandibular reconstruction following mendibulectomy, alveolar ridge reconstrution is indispensable. Porous hydroxyapatite blocks can freely make peculiar form of the mandible. The material fragility can conquer by using metal reconstruction plate. And free forearm flap, which is currently the most thin large flap, can fully correspond to large defect of the oral mucosa. Since 1985, we have performed 39 cases of the alveolar ridge reconstruction by porous hydroxyapatite block and free forearm flap. Although neccesity of more improvement we can set usual type of prosthesis without resections-prosthesis.
In this paper, the authors describe our alveolar ridge reconstruction method by demonstrating recent case.

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Autogenous iliac particulate bone and marrow (PCBM) grafts have many advantages, such as high cellular content, early bone formation, ease of moldability, and other beneficial characteristics. For these reasons we perform mandibular reconstruction using PCBM grafts. The PCBM and two cortical bone plates are separated from a block of iliac crest. The PCBM, with bone plates serving as a tray, is then used to reconstruct the mandible. Results of a morphologic study, our clinical experience with this method, and the application of dental implants to the grafted area are described in this paper.

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The surgery for head and neck cancers invading cavernous sinus has still controversy, because both the sufficient prognosis and the probabiliy of radical excision are not expected in such advanced cases. From 1986 to 1992, we experienced combined resection of cavernous in 8 patients of head and neck malignancies with cavernous sinus involvement. The procedure of surgery of thses 8 patients were combinaton of transcranial and tranfacial approach followed by skull base reconstruction using free musculocutaneous flaps. 4 patients (one: osteosarcoma, 3: adenoidcystic carcinoma) are still alive without recurrence more 21 months after surgery. 2 of 4 patients of squamous cell carcinoma died in less than 10 days after surgery due to carotid thrombosis. another 1 of 4 had a hemiplegia due to carotid thrombosis. Another one of 4 is alive without any major complications 6 months after surgery.
As a result that the 4 patients with cavernous sinus involvement are alive after surgery, the combined resection of the cavernous sinus can be indicated in some cases with cavernous sinus involvement of the head and neck cancer.

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We have performed en bloc craniofacial resection containing both anterior and/or middle cranial base for the extensive nasal and paranasal sinus carcinoma invading the skull base since 1987, and we also proposed a new method of the intradural resection of the extensive cancer in 1990. En bloc resection of both anterior and/or middle cranial base with a maxillofacial segment is composed of two kinds of bone cutting lines on the skull base, one of which is a sagittal line throgh the cribriform plate and the other is a transverse line throuth the foramen ovale from the mandibular fossa to the carotid sulcus on the middle cranial base, and which access over the sphenoid body between the planum sphenoidale and the carotid sulcus. The area surrounded by these osteotomy lines contains the base of the pterygoid process, the superior orbital fissure, and the foramen rotundum where nasal and paranasal sinus carcinomas frequently invade. The en bloc resection is not considered to be indicated from such investigations as CT, MRI, 3D-CT and large sectioned specimens, in cases when such cancers invade further deep beyond the posteromedial margins of this area into 1) the sphenoid body, 2) the sphenoclival junction, 3) the cavernous sinus 4) the foramen lacerum and around the interal caratid artery and/or 5) the dura near this area with skip lesions on the skull base.

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For the surgical treatment of the benign or low grade malignant tumors in the skull base, the minimum cosmetic or functional deformity are required. However, the surgical access to the skull base is very difficult because this area is surrounded with facial skeleton and dense connective tissue. We usually employ two approaches for the treatment of the skull base tumor. One is a transfacial approach and another is a lateral approach.
In order to gain a good access using these approaches and minimize the morbidity, anatomic study of the skull base was performed. The findings indicate that several anatomical landmarks can be utilized in order to identify the vital structures in the skull base.

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The combined craniofacial approach was performed for en bloc resection of the sino-nasal cavity carcinoma invaded to skull base, orbit, temporal fossa, pterygopalatine fossa, et al.
Occasionaly, the cancer is not free, histologically, in the carcinomas of en bloc resection with safety margin. And so, we suggest that the histopathological study of the style and direction of cancer invasion is necessary by the microscopic observations in extra large specimens. We performed the histopathological study on the sino-nasal cavity carcinoma invaded to skull base by the microscopic observations in 9 extra large specimens of 15 cases of skull base surgery.

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Anterior skullbase surgery with transbasal approach via frontal craniotomy has been performed in fifteen cases. Eleven patients underwent combined transbasal and transfacia procedure. Eleven cases were the malignant tumors of paranasal sinuses and nasal cavity.
Galeopericranial flap were used for the reconstruction of the anterior skull base. The patients in this series suffered no major complications such as CSF leak, meningitis, flap necrosis. The patients who underwent combined procedure and were widely resected of facial and nasal bone structure had minor deformation of feature and nasal dysfunction. On the other hand four patients who underwent transbasal procedure alone could be remained the normal nasal function and feature. We can get the good access to the nasal cavity by transbasal approach rather than by transfacial approach, and we can extend the operation field further more with osteotomy of supraorbital bar. The transbasal approach is the first choice of procedure for en bloc resection of tumor of the paranasal sinuses and nasal cavity invading to the anterior cranial fossa.

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Anterior skull base surgery employing a team approach was introduced with a report of a typical case. In total 13 patients (11 cases with malignant tumor and 2 cases with benign tumor) underwent this surgery. Five cases showed recurrence of their disease. In these five five cases, two died from primary lesion and one died from distant metastasis. Another two recurrence cases under went secondary therapy and are now free of tumor. Other eight cases are now free of recurrence and in total 10 cases are still alive free of tumor. Three year survival rate using Kaplan-Meier method is 69% in total and that of the 11 cancer cases studied is 66%.
Advantages of this team approach are: 1) otolaryngologist can concentrate his effort on removal of the tumor, 2) operationgoes smoothly with a better result, 3) patients can obtain the best after-care.
We should bear in mind that the final outcome of the team approach is depending mainly upon the specialist whose level is lowest in the team.

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This study is on-going as Group Study supported by Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan. Ninety-three cases were collected from 8 institutions, and were analyzed. About 89% of the patients have malignant tumors of the nose and paranasal sinuses. As for the histologic type, squamous cell carcinoma is most common in 49 cases, followed by olfactory neuroblastoma in 11, adenoid cystic carcinoma in 10, and so on. Sixty-three patients had no prior treatment. In terms of craniotomy, we performed frontal craniotomy in 30 cases, fronto-temporal craniotomy in 30, and so on. As for repair of dura mater, fascia lata was used in 24 cases, then pericranial flap in 13, and galeopericranial flap in 11. For reconstruction of the skull base and the face, free rectos abdominis flap was most commonly used in 59 cases. The 5-year survival was 40% for all the patients, 45% for squamous cell carcinoma, and 50% for adenoid cystic carcinoma. The results obtained were very encouarging. The incidence of surgical complication was 36%.

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Fourteen patients underwent reconstruction of skull base defects between 1989 and 1993. In this series, two patients required reoperations because of postoperative extradural abscess. Statistical analysis of the results of our series shows that the use of a bone graft is significantly associated with postoperative wound infection (p=0.033: Fisher Exact test). Although both patients with postoperative wound infections had preoperative radiation therapy, this is not significantly associated with infectious risk (p=0.308). The size of a bony defect, selection of a flap, and materials for a dural graft are not also significantly associated with postoperatve extradural abscess in this series. Eventually, all but one patients were well reconstructed without bone grafts. We feel that the use of bone grafts in reconstruction of skull base defects could lead to dead space and an increased chance for infectious complications. Although the number of patients in this series is not large, this study demonstrates that the use of bone grafts in reconstruction of skull base defects could be one of the factors in increasing the chances of infectious complications. We think that a bone graft is not necessary to reconstruct a moderate-sized skull base defect.

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According to current concepts of cancer therapy, the platinum coordination complexes can modulate radiation damege. Past Clinical data indicate encouraging preliminary results with concurrent cisplatin and radiotherapy. Carboplatin (CBDCA, Bristol-Myers), a second generation platinum analog has comparable antitumor activity in the head and neck cancer but less toxicity than cisplatin. In order to evaluate the efficacy and safety of concurrent CBDCA and radiotherapy, previously untreated 138 patients (pts) with head and neck carcinomas were treated with weekly CBDCA at 100mg/m² given simultaneously for the conventional radiotherapy (2.5Gy×4/week) from November 1990 to June 1994. At the dose of 40Gy, pts were evaluated. NC cases underwent planned surgery and PR+CR cases continued this modality up to a dose of 65 Gy.
Of 107 evaluable pts, 71 (66%) had a alive without disease and 42 month survival rate (Kaplan-Meier mothod) revealed 57% as a whole. Toxicity over Grade III was primarily hematological. Leucocytopenia was observed in 13cases (9.8%), thrombocytopenia in 4 cases (3.0%) and mucositis in 8 cases (6.0%) out of 132cases. Fortytwo months survival rate in laryngeal carcinomas revealed 89%. From the viewpoint of organ/function preservation, the laryngeal preservation rate was 74% (20/27) in T2, 71% (5/7) in T3 and 33% (1/3) in T4 cases. We considered this treatment modality demonstrating fairly well 42 months survival rate and the laryngeal preservation rate particullary in T3 cases to be a significant choice of treatment in laryngeal carcinoma.

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Carboplatin, a second-generation cisplatin analogue, has shown potentiation of radiation effect comparable with cisplatin in vitro and in vivo.
Furthermore, carboplatin has antitumor activity comparable with cisplatin in head and neck squamous cell carcinoma (SCCHN). To determine toxicity and response, carboplatin was given simultaneusly with stage 3 and stage 4 disease of SCCHN. Caboplatin was given weekly in the dose of 75mg/M² during radiation therapy. Twenty-two patients showed CR (68.8%) and total response rate was 93.8%. Two patients showed NC. Thirteen patients with CR have no recurrent disease, and 5 patient have been alive without disease for more than 2 years. As for nasopharyngeal cancer, 7 patients out of 11 showed CR and all the seven patients have been alive without recurrent disease. Ten patients showed stomatitis (31.3%) and 5 patients showed leukopenia (15.6%). The toxic effects were reversible and all the patients could accomplish this regimen. Simultaneous Carboplatin and radiotherapy seemed to have tolerable toxicity and excellent effect against advanced SCCHN.

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One hundred and twenty-eight patients with advanced head and neck squamous cell carcinoma were entered in to a feasibility stydy of low-dose cisplatin (CDDP) with concurrent radiation therapy. Minimum follow-up time was 1 year. As an intial treatment, the radiotherapy regimen consisted of 1.8-2.0Gy given 5 days a week for 4-5 weeks (40-50Gy), and the CDDP (daily dose of 5mg m² or 6mg/body, iv) was administered of a loco-ragional major response (complate+partial) within 2 weeks after completion of initial treatment was 95%. Thirty-one patients underwent surgery, and 87 patients had boost radiation (10-25Gy), although 10 patients refused additional treatment. The 1-year relapse-free survival rate for oropharynx (37pts), hypopharynx (11pts), glottis (16pts), and supraglottis (16pts) were 74%, 80%, 62%, and 84%, respectively. The 1-year cause-specific survival for those were 92%, 100%, 100%, respectively, the high response and survival rates obtained.

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Thirty-two patients with squamous cell carcinoma of head and neck which had no distant metastasis were treated with radiotherapy combined with chemotherapy (Cisplatin based chemotherapy) at Department of Radiology, Sapporo National Hospital, Hokkaido Cancer Center. Primary Lesion were 12 patients with nasopharyngeal cancer, 8 patients with oropharyngeal cancer, 5 patients with hypopharyngeal cancer, 5 patients with tongue or intraocular cancer and 2 patients with laryngeal cancer. There were twenty-seven male patients and five female patients. The age range was 20 years to 72 years with a median of 58 years. Twenty-five patients had grade 1 of performance status, 2 patients had grade 2, 2 patients had grade 4 and none had grade 3.5 year survival rate of all patients was 44.2%, of patients with complete response (CR) was 67.8% and of patients with partial response was 0%.
CR rate of patients with concurrent combination of radiation and chemotherapy was 71.4% (10/14) and non-concurrent combination (neo-adjuvant or adjuvant) was 72.2% (13/18). Survival rate of two group was almost same. Acute reactions of pharynx of patients with concurrent combination was more severe than non-concurrent combibnation. Then treatment time of concurrent combination was longer than non-concurrent combination.

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Radiotherapy combined with chemotherapy is still used for standard treatment in patient with locally advanced unresectable cancer.
A study was undertaken to compare a sequential (neo-adjuvant) with a simultaneous (concurrent) chemotherapy and radiotherapy program.
Neo-adjuvant chemotherapy with cisplatin (80mg/m² i. v. day 1) and 5FU (600mg/m² continuous i. v. day 1-5) every 3 weeks prior to definitive conventional radiotherapy (60-65Gy), or cisplatin (20mg/m² i. v. day 1-5) and 5FU (250mg/m² continuous i. v. infusion, day 1-14) were given simultaneously for same radiotherapy.
Complete response rate was 45% in the sequential treatment and 43% in the simultaneous arm.
Leukopenia and other adverse effect were obtained sligthly more frequeut in the simultaneous arm, but there were no sigmificant differences.
These results suggested that individualization of treatment planing and establishment of optimum treatment were most important for combination of chemotherapy and radiotherapy.

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In human thyroid tissues obtained surgically from 3 non diseased tissues, 2 Graves' diseases, 3 follicular adenomas, 3 papillary carcinomas, 4 follicular carcinomas, cathepsin L activities were measured and elastin was stained. These results were compaired with histopathological findings, extracapsular invasion and metastasis.
Mean of cathepsin L activity in malignant diseased group significantly showed higher than in normal thyroid group. There were found no relationship between cathepsin L activity and TN M classification. But thyroid tissues with destructions of elastin and hard cell proliferation ha da tendency to show high cathepsin L activity.

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