When apply the osseointegrated implants especially in bone grafted bed and irradiated site after cancer treatment, it is indispensable to understand the proper treatment procedures and the scientific background such as bone healing and remodeling around implant fixtures to restore the jaw function and esthetics. In the paper, we showed the treatment steps of osseointegrated implants and the bone healing process around fixtures in animal study. In addition, bone healing and remodeling in case of long-term loaded implants and implant placement in bone grafted site and irradiated bed in human jaws, were histologically analyzed using retrieved specimens.

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Patients who have undergone resection of oral tumors suffer from disorders of oral functions, restoration of which is a great challenge for clinicians. In this paper we present our experiences in rehabilitation of oral functions with dental implants in patients who have been treated for oral tumors. The dental implants used in this study were apatite flame-sprayed titanium with an overlay denture-type superstructure. Our experiences strongly suggest that bone-anchored dental prostheses are useful for the rehabilitation of masticatory and speech functions.

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Conventional treatment of jaw reconstruction with autogenous bone graft and titanium plate is not able to recover the function of mastication. In such cases we have tried to apply dental implants for the denture after resection of mandible. Bränemark implant system was applied to the iliac bone transplant after tumor surgery. And we obtained excellent stability of the denture and the function of mastication.
Surgical techniques were demonstrated with video and various problems about implant denture were discussed.

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We have developed maxillofacial prosthesis using direct bone anchorage by extraoral placement of osseointegrated implant. Many of the previous limitation of conventional maxillofacial prosthesis mainly caused by less stability have been minimized by this method. Whenever possible, the treatment of choice for a craniofacial defects is surgial reconstruction of the part. The etiology of craniofacial defects falls into three group; 1) Congenital absence 2) Traumatic loss 3) Surgical removal. Surgial procedure and prosthodontic treatment are basically same as those of usual dental implant tratment; 1) Fixture installation 2) Abutmen connection 3) Impression 4) Facial cast model 5) Mental frame wark 6) Wax prosthesis forming 7) Plaster model 8) Silicon prosthesis. In Department of Oral Surgery, Nagoya University Hospital, seven orbital prosthesis, three auricular prosthesis and one nasal prosthesis of this type of treatment have been performed. As a result, this group of patients can well rehabilitated to a higher level and many such individual enjoy greatly improved lifestyle. However, long long-term success depend on an intimate understanding of the variables involved and total comitment to the multidiscipinaly teamwork philosophy of treatment. In this paper, general concepts of this kind of treatment were introduce and presented the representative cases.

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Reconstruction of the masticatory function with osseointegrated implants involves troublesome and challenging problems in resected jaw cases.
Twenty eight patients whose jaws were resected due to the tumor or the cyst were analyzed clinically.
The problems, reported in this paper, affecting the implant rehabilitation were as follows. 1) Anatomical structure of jaw bones
2) Morphology and location of the residual jaw bone
3) Size and shape of the grafted bone
4) Incompatibility of the skin flaps surrounding the implants
5) Handling of the instrument to set up implant denture into the mouth
6) Timing of the implant rehabilitation after tumor surgery
7) Success rate of osseointegrated implants into reconstructed jaw
8) Cost for implant rehabilitation
Dental implants provide the optimal functional and cosmetic rehabilitation for patients who have sustained disabling deformity. However we must solve the many kind of problems concerning with the application of the dental implants to the resected jaws.

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This paper described our principle and the outlin of the surgery for laryngeal carcinoma, and the most popular two basic surgical procedures, i. e. frontolateral partial laryngectomy and total layngectomy, which were presented with VTR in the symposium.
To prevent the recurrence, it is mandatory to evaluate the extent of the lesion accurately by endoscopy, CT, VTR and so on, and to make sure of it directly through the operation.
Our method for the direct ascertainment in total laryngectomy is to open the larynx, which is reversed after separating from the trachea, by resecting the cricoid lamina in the midline with scissors.
The rate of local recurrence of total laryngectomy was only 3/420 (0.7%) at our clinic. From this result, our method seemed to be very effective.
On the other hand, those of partial laryngectomy were 5/44 (11.4%) for the initial treatment, 3/29 (10.3%) for the salvage of failure which had been irradiated at our clinic and 3/13 (23.1%) for the salvage of failure irradiated at other clinics. This result suggested that the information of the tumor's extent before radiotherapy was very important, if partial laryngectomy was indicated.
The goal of surgery for laryngeal carcinoma is not only to iradicate the lesion but also to preserve the functions.

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1) Among 24 parotid cancer patients which we operated during 1985-1989, definite preoperative diagnosis of malignant tumor could not be obtained in 5 cases after evaluation of signs and symptoms, ultrasonography, MRI, sialo-CT and find needle aspiration cytology. These cases consisted either of the small tumor without apparent invasion, the low grade malignant tumor or the cystic tumor. 3 cases with high grade malignant tumor received fast neutron irradiation postoperatively. All are living free of tumor for more than 5 years at the present time. However one developed postradiation myelopathy. For fine needle aspiration cytology in cystic tumor, utmost attention should be paid to obtain cytology materials from solid portion of the tumor.
2) In one patient with pleomorphic adenoma of the parotid gland, we performed fine needle aspiration cytology 4 months preceding superficial parotidectomy. In serial section of the surgical specimen, we observed a microscopic second tumor 0.5×0.5mm in diameter, adjacent to the main tumor in direction to which an aspiratiom needle was inserted. Aspiration cytology should be performed in selected cases in which definite diagnosis of benign tumor can not be obtained after ultrasonographic examination with recognition that it may cause dissemination of the tumor cells along the needle.
3) During 1978-1993 we operated 15 cases of recurrent plemorphic adenoma of the parotid gland. Among 15 cases the tumor was multiple in 12 cases and 7 cases visited us after the second or the third recurrence. First recurrence was noted more than 5 years after the initial operation in 13 cases and after more than 10 years in 6 cases. Malignant transformation developed in one of two case who had the third recurrence. In all except one who had malignant transformation, we preserved facial nerve with residual minimum facial nerve palsy in 3 cases. For prevention of recurrence in plemorphic adenoma, complete preservation of the tumor capsule is essential in the initial surgery.

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According to UICC, the oral cavity is classified into six sites and there are different problems depending upon subsites where operation is performed. This time, basic operative procedure for lower alveolus and gingiva was presented, because the operation for mandibular malignant tumor included typical difficult problems antomically related such as airway obstruction, temporomandibular disturbances, proper occlusion, prosthetic device, facial cosmetics etc. The present operation consisted of upper neck dissection, continueous resection of half mandible except for condyle head and reconstruction using titanium mandibular reconstruction plate. For the treatment of malignant tumor, the complete en bloc removal of tumor is very important. However, we should try to keep oral function and facial cosmetics as possible. Consequently, we should recognize the accurate condition at first consultation by inspection, palpation and various kinds of imaging examination such as radiography, CT, MRI etc. Moreover, histopathological type and histopathological grade of malignancy should be taken into acount. Then, the decision of the resection area with an adequete safety surgical margin is made according to the above factors. Extraoral incision was made parallel and 3 cm below the inferior border of the mandible. During operation, mandibular branch of facial nerve, facial artery and vein, hypoglossal and lingual nerve, inferior alveolar neurovascular bundle so on were identified and some were cut and ligated and some were left. Before resection of the mandible, reconstruction plate was adapted and temporary fixed to retained mandible to keep proper position. Then, the plate was once removed and the mandible was resected using Gigli saw and bur. The mandible was rotated laterally and the connected soft tissues were incised along the medial aspect of the mandible. After the en bloc removal of tumor, reconstruction plate was rigidly fixed at the same position as it was temporary adapted. At first intraoral sutures were made. At that time, for fragile soft tissues matress sutures were acompanied with single sutures. After that instruments were renewed and the wound was washed out with saline. Then, skin sutures were carried out by 5-0 monofilament nylon after continueous beried sutures by 3-0 PGA.
Conclusively, accurate recognition of the tumor condition and the knowledge of surgical anatomy were the most important to avoid functional and cosmetic disturbances as was classically stated.

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During the last four years, a total of 125 cases with head and neck defects were repaired with 151 free tissue transfers. Among them, anterolateral thigh flap (33 flaps), anteromedial thigh flap (19 flaps), combined flaps with anterior thigh flap (33 flaps), abdominal flaps (19 flaps) including rectus abdominis flap, radial forearm flap (15 flaps), and others. Regarding indications of these flaps, radial forearm flap is used for resurface small and thin defects. Large and thick defects are repaired with rectus abdominis MC flap and anterior thigh flaps. Forearm flap can be transferred as osteocutaneous flap, tendocutaneous flap with the palmaris longus tendon, and sensory providing flap. Rectus abdominis MC flap can be used as reduced muscle MC flap, perforator-based flap, and thin flap. Anterior thigh flaps can be applied as FC flap and combined flaps such as thigh flap-iliac bone, thigh flap-groin flap, and thigh flap-abdominal flap-iliac bone.

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Erythropoietin (EPO) is a hematopoietic growth factor which stimulates the production of red blood cells. EPO has been widely used in various fields of clinical medicine including the therapy of renal anemia. Intravenous or subcutaneous administration of EPO is also effective in the treatment of the anemia of cancer. EPO administration to anemic cancer patients brings about the improvement of anemia and quality of life of cancer patients. EPO is also useful in autologous red blood cell transfusion resulting in prevension of development of anemia.

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G-CSF is applied to various fields in cancer chemotholopy. Myeloid leukemia cells have often G-CSF receptor.
Administration of G-CSF to myeloid leukemia needs carful observation.
For infection in patients with hematological diseases non responders to 3 day antibiotic therapy were randomized to two groups of antibiotic therapy with or without G-CSF. Significant difference in the response rate was obtained. In bone marrow transplantation G-CSF treated group showed significantly shorther granulocyte recovery. After 5 year follow up the group showed also significantly lower incidence of chronic GVHD. This data is now reexamined in the international cooperative study of Asian Pacific BMT study group.

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Peripheral blood stem cells (PBSC) are increased transiently but substantially during hematologic recovery from myelosuppressive chemotherapy. Mobilization of PBSC is enhanced effectively when G-CSF is administered prior to PBSC collection during the hematologic recovery. These PBSC can be collected by apheresis using a continuous blood cell separator. Hematological reconstitution after marrow-ablative therapy is feasible by autologous PBSC transplantation (PBSCT). Autologous PBSCT has been increasingly used in the treatment of hematologic malignancies and solid tumors. Recent clinical trials clearly indicate that PBSCT is characterized by rapid hematologic recovery and low transplant-related mortality, and clinical results of high-dose chemotherapy facilitated by PBSCT seem to be encouraging. Autologous PBSCT provides several advantages over autologous bone marrow transplantation (BMT). They include 1) rapid hematologic engraftment, 2) avoidance of risks and discomfort associated with general anesthesia, and 3) less requirement for blood transfusion, antibiotic therapy and hospitalization days. Furthermore, it has been demonstrated that G-CSF alone can mobilize a large number of PBSC in heathy adults. These observations strongly suggest that allotransplantation of G-CSF-mobilized PBSC from normal donors as an alternative to bone marrow may be feasible in humans. Some successful cases of allogeneic PBSCT have been reported. Further experience with more patients and longer follow-up will be required to assess the efficacy and feasibility of allogeneic PBSCT.

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Stem cell factor (SCF), is a ligand for c-kit, has a broad range of acitvities including effects on cells at or near the level of the multipotential stem cell as well as on committed cells. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow celluarity, and increase circulating periperal blood stem cells (PBSC).
Recombinant human SCF has clinical potential through its synergy with other cytokines, especially granulocyte colony-stimulating factor to enhance mobilization of PBSC.

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Various cytokines have been investigated to test the effect on thrombocytopenia. Interleukin-3 has escalated nadirs of thrombocytopenia induced by chemotherapy and promoted recovery of thrombocytopenia. Major toxicities occured were fever, flu-like symptomes, headache and othtrs but these were relatively mild.
Interleukin-6 has shown effect on thrombocytopenia induced by chemotherapy but toxicities such as fever, fatigue and others were relatively severe.
Interleukin-11 has shown thrombostimulatory effects in phase I trial and phase II trials are in progress.
Thrombopoietin has demonstrated stimulatory effects on production and maturation of megakangocyte and has promoted recovery of thrombocytopenia induced by chemotherapy and radiotherapy. Phase I trials are in progress in western countries.

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Biological evidence supporting the effectiveness of hyperfractionation, accelerated fractionation and accelerated hyperfractionation was discused in the treatment of head and neck cancers. A number of clinical trials on altered fractionation schedule have shown an improvement in the local control of advanced head and neck cancers. Despite of the clinical improvement, altered fractionation has a limitation for the local control of large tumors caused by increased in situ cellular radioresistance rather than large number of tumor cells. This was shown by multivariate analysis of the data on cervical lymph node-metastases.

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It is not known why nose remains to be nose after radiotherapy of nasal cancer. Molecular biology behind the mechanism of morphological preservation by radiotherapy comes to be investigated. Fibroblasts surviving after 10Gy irradiation seemed to produce more chemoattractant than non-irradiated fibroblasts. Anti-fibrinonection and anti-hepatocellular growth factor made the cell motility smaller. These substance may be one of the chemoattractant produced by the fibroblasts after irradiation. Cadherin was demonstrated on the cell surface of laryngeal epithelium even 5 years after the irradiation of 65Gy in 26 fractions. Administration of cell adhesion molecules and growth factors may have a role to improve radiotherapy in future. Stereotactic technique and the understanding about volume effect is now improving the accuracy of radiotherapy dramatically to preserve morphological and functional status.

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Diagnostic imaging in the head and neck has evolved as a result of continuing technical advances. The utility of ultrasound in the evaluation of lesions of the neck is well established, particularly in the thyroid glands. MR imaging may offer more information on the precise characterization of tumors and on the determination of tumor extent than CT in the head and neck region. So we have to choose the opitimal modality of imaging depening on the region of the head and neck.
Magnetic resonance (MR) imaging is widely used in evaluating various lesions of the head and neck. By providing shorter imaging times with comparable image contrast and quality, Fat-suppressed MR imaging shows promise in replacing T₂-weighted fast-spin-echo (FSE). Fat-suppressed MR imaging is T₂-weighted fat-suppresed FSE or STIR. Usually these images improve visibility of small lesions and early changes secondary to spread of tumor. The radiologist have to consider increasing patient's cooperation and throughput while decreasing cost.

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Based on the Phase I/II study, from January 1992 through December 1993 we treated 49 head and neck carcinoma in 48 patients with high dose rate fractionated interstitial radiotherapy (HDR-ISR) using micro Selectron. Local control rate of HDR-ISR for tongue carcinoma was higher than that of LDR continuous radiotherapy using ²²⁶Ra needles or ¹⁹²Ir hair pins. There are three major advantages in HDR-ISR compared with low dose rate continuous radiotherapy. 1) Complete fixation of guide applicators during the interstitial treatment resulted in the accurate estimation of the dose distribution. 2) The source arrangement of HDR brachytherapy using the linked double-button technique is better than that of LDR brachytherapy. 3) Using dose optimization program of dose distribution, the more homogeneous dose distribution can be obtained. HDR fractionated interstitial radiotherapy can be an alternative to traditional LDR interstitial radiotherapy.

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Sharply defined distribution is important characteristics of heavy charged particle therapy delivering high treatment dose to the target volume and reduced irradiation dose to the surrounding normal tissues. A pilot study of heavy charged particles with Heavy Ion Medical Accelerator in Chiba (HIMAC) for advanced H & N cancer has been carried out from June 1994 at National Institute of Radiological Sciences (NIRS). As of the begining of August 1994, three patients were treated by 290MeV carbon ions. The patients had adenocarcinoma of the cheek mucosa, squamous cell carcinoma of the ethmoid sinus and adenoid cystic carcinoma of the sublingual gland. Patients were immobilized by individual head coach and thermosplint facial shell. Individual collimators and boulous were also prepared for each ports. Dose fractionation for the initial pilot study group was 16.2GyE/18 fractions/6 weeks, which would be equivalent to standard fractionation of 60.0Gy/30 fractions/6 weeks with photons. This dose fractionation was considered to be 20% lesser than 75GyE/37.5 fractions/7.5 weeks, which is estimated to be maximum tolerance dose for advanced H & N cancers. HIMAC worked well and there was no major trouble causing any treatment delay. Acute skin reactions of 3 patients were 2 cases of bright erythema with patchy moist desquamation and one of dull erythema, which were evaluated as equivalent reaction with irradiated dose. Acute mucosa reactions appeared to have less reaction than predicted mucositis. Tumor reactions of three patients were partial reaction (PR) at the end of treatment and nearly complete remission (CR) after 6 months of treatment. From October 1994, we started to treat patients with advanced H & N cancer with 10% high dose than previous dose. And new candidates of pilot study with non small cell lung cancer, brain tumor and carcinoma of the tongue were entered into pilot study. At the end of February 1995, a total of 21 patients were treated by carbon ions.

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