When total thyroidectomy is performed without regard for the parathyroid glands, permanent hypoparathyroidism is a frequent result. To avoid the hypofunction, it is necessary to presrve the blood supply of at least one gland or transplant more than two glands of the parathyroid.
The superior parathyroid gland generally lies along the posterior aspect of the thyroid at the crico-tracheal junction. It is a small lustrous oval of about 5mm, its color a pale orange (similar to that of sea urchin).
Method of preservation: The superior parathyroid gland and inferior parathyroid artery are identified and gradually dissected away from the thyroid. If there is a feeding artery from the posterior branch of the superior thyroid artery, this should be preserved.
Method of autotransplanation: The parathyroid glands which can be transplanted after total thyroidectomy should be removed at once. A slice of tissue is submitted for frozen section study to assess histologically. The gland is cut into slice (10-15 slices) using a fine pair of scissors. Several transplantation beds are made in the muscle of the neck and chest (the pectoralis major, sternocleidomastoid and posterior neck muscle) to transplant the slices. Knowledg of the anatomy and careful technique are required when operating on the parathyroid glands.

View full abstract

Result of operation in 83 cases of hyperparathyroidism (Primary 33 cases and secondary 50 cases) were reported and operative procedures were disscussed
It was a principle in our surgery that all of the four parathynoids glands must be searched without reference to preoperative diagnosis.
Result were succeeded in all cases except a cese in secondary.

View full abstract

Since 1976, parathyroidectomy was performed in 132 patients with primary hyperparathyroidism and in 31 patients with secondary hyperparathyroidism. Adenoma, in 110 cases, was the most common type of pathology found. Carcinoma was found in nine cases. Of the hyperplasia in primary hyperparathyroidism, two were multiple endocrine neoplasia type 1.
Principles of parathyroid explorations summarised by H. A. Bruining were modified as follows
1. Gain practice during thyroid operations
2. Knowledge of normal anatomy and variations
3. Schematic approach
4. Bloodless field
5. Resect enlarged glands only
6. Unilateral neck exploration in cases of adenoma
7. Beware of supernumeraly glands in hyperplasia
8. Avoid tumor cell dissemination
9. Minimal scar formation
To achieve schematic approach under bloodless field, a conscientious separation of the sternothyroid fascia, surgical capsule and anatomical capsule of the thyroid was emphasized.

View full abstract

There are several surgical approaches to tumors of the parapharyngeal space. The choice of surgical approach depends upon the tumor size, location and vascular status, and on the degree of suspicion of malignancy preoperatively. A transparotid approach is one of sugical exposure for tumor resection. In this paper, I reported the main application and surgical technique of the transparotid approach to the parapharyngeal space tumors.

View full abstract

The push up method, a new surgical approach to the parapharyngeal space, is described. The essential points of the method are 1) mucosal incision of the oral floor is minimized for mandibulotomy, and 2) the resected mandibula is pushed upward rather than swung back as in the conventional method. The advantages of the method are 1) an adequate surgical field can be achieved in a short period of time, 2) postoperative trismus and masticatory disorder are mild, and 3) sensory disturbance and never damage are rare. It is possible to immediately switch to the mandibular swing method, if it is necessary. A surgical scar remains over the mental region to the lower lip, which is an only one disadvantage of the method. The push up method is useful for resection of most benign tumors arising in the parapharyngeal space. The indication of the method depends on the location of tumors. Tumors should be directly inspected during surgery. In cases where the tumor is superiorly located adjacent to the skull base, other methods with more adequate exposure should be used.

View full abstract

The midline mandibulotomy, a procedure to the parapharyngeal space, is generally preceded by splitting a lower lip. This incision often creates the cosmetic problem of the potoperative scaring in the midline face. Here, we report a procedure to avoid this problem by forming a flap of a lower lip.
The skin incision extends to the contralateral mental foramen over the hyoid bone. After the division of the mental nerve and the mucosal incision along the gingivobuccal gutter, the lower lip, cheek and masseter muscle is elevated as the strap flap (visor-like flap) from the mandible. This flap makes it possible to perform the midline mandibulotomy without split of the lower lip. The oral cavity is then widely exposed by rotating the flap upward as a visor over the upper lip. The parapharyngeal space is opened widely by retracting the mandible latelally and superiorly.

View full abstract

Removal of tumors from the parapharyngeal space is often difficult because of limited surgical access. The surgical approaches to the parapharyngeal space include: 1) transcervical approach, 2) transparotid approach, 3) intraoral approach, 4) mandibular swing approach and so on.
In this paper, we discuss surgical approaches to the parapharyngeal space tumors by the horizontal osteotomy of the ascending ramus of the mandibule. The inferior alveolar nerve can be preserved by making a burr hole around the mandibular canal prior to osteotomy. We present two cases of large pleomorphic adenoma occupying the parapharyngeal space which were totally excised by this approach. Our lateral mandibular osteotomy provides an excellent access to the space avoiding damage to the inferior alveolar nerve.

View full abstract

In this paper, we presented the surgical techniques of intracranial facial nerve reconstruction and evaluated the postoperative facial nerve function.
We have used four methods for the intracranial facial nerve reconstruction; 1) End-to-end anastomosis, 2) Re-routing (re-route the facial nerve from Fallopian canal to the internal auditory canal), 3) Transposition of GPN (re-route the greater superficial petrosal nerve to the internal auditory canal), and 4) Sural nerve graft. One of the benefits of the intracranial facial nerve reconstruction is that we can perform these procedure in the same surgical field as the tumor removal.
Although the facial nerve function was excellent in any type of those four intracranial reconstruction methods, the facial score after the end-to-end anastomosis was the best after more than 1 year follow-up. In 7 out of 9 patients after the end-to-end anastomosis, the facial nerve function was grade II or III in House-Brackmann grading system.
Thus, we highly recommended the intracranial facial nerve anastomosis to repair the intraoperative facial nerve damage in the internal auditory meatus. The end-to-end anastomosis should be done as a first choice for the facial nerve reconstruction.

View full abstract

Nerve grafting has been accepted as the surgical choice for facial rehabilitation when facial nerve is sacrificed and end to end anastomosis is unsuccessful in ear surgery or acoustic neuroma surgery. The greater auricular nerve is most commonly used for grafting due to its appropriate diameter and accessibility. When the proximal facial nerve is unavailable or unsuitable for reanastomosis, hypoglossal nerve is commonly employed as nerve substitution. The hypoglossal-facial anastomosis bring good facial symmetry at rest and voluntary movement one to two years postoperation, although hemitongue paralysis and severe synkinesis occurs. To address the drawbacks and limitation of the classic procedure, hypoglossal-facial jump graft is developed. This procedure involves interposing a nerve graft between a partially severed but functionally intact hypoglossal nerve and degenerated facial nerve. The advantage of this procedure is to prevent hemitongue paralysis and to minimize synkinesis, although the recovery of the voluntary movement dose not appear to be as strong. To achieve good reanimation of the paralyzed face, other reanimation procedures such as suspension and muscle transposition should be combined with above neural reanimation.

View full abstract

Recently, several genes encoding tumor rejection antigens recognized by cytotoxic T lymphocytes (CTL) have been identified. We investigated the expression of MAGE-1, MAGE-3, and GAGE genes in 108, 111, and 63 patients, respectively, with squamous cell carcinoma of the head and neck (SCCHN). Reverse-transcription and polymerase chain reaction (RT-PCR) analysis using primers specific for each gene revealed that MAGE-1, MAGE-3, and GAGE genes were expressed 27.8%, 47.4%, and 41.3% of patients with SCCHN, respectively. We also tried to achieve in vitro CTL induction against MAGE-3 encoding tumor rejection antigen (FLWGPRALV), which is presented by HLA-A2 molecule, using peripheral blood mononuclear cells (PBMCs) from HLA-A2-positive donors. Dendritic cells were propagated from the PBMCs with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The dendritic cells were pulsed with the peptide FLWGPRALV and used as antigen-presenting cells. The PBMC including the peptide-pulsed dendritic cells, were cultivated with medium containing IL-1, IL-2, IL-4 and IL-6. These in vitro -induced effector cells showed significant cytotoxicity against a SCCHN cell line expressing both HLA-A2 and the MAGE-3 gene. These results suggest that patients with SCCHN would be good candidate for specific immunotherapy against tumor antigen peptide.

View full abstract

Apoptosis is a programmed cell death that is activated under physiological conditions and may be an important safeguard against tumor development.
Fas antigen of the cells has been well-known as a membrane protein that mediates apoptosis. The Bcl-2 protein promotes cell survival by preventing the onset of apoptosis.
In this study, we show the role of Fas and Bcl-2 expression in the induction of apoptosis by cisplatin (CDDP) in vitro. The treatment of cancer cell lines with antisense oligonucleotides for bcl-2 gene decreased Bcl-2 protein level, and augmented cell death induced by CDDP. Also, we demonstrate some significant correlations between Fas or Bcl-2 protein by an immunohistochemical approach and chemo-sensitivity measured by ATP assay in head and neck cancers. These results suggest that regulation of Fas and Bcl-2 expression may have clinical potential in chemotherapy.

View full abstract

To detect chromosomal abnormalities on tumor cells in early stage and chromosomal changes depending on tumor progression, DNA cytofluorometry and fluorescence in situ hybridization (FISH) were performed. 13 tongue carcimomas and 16 thyroid carcinomas were investigated about ch1, 7, 11, 17, X, Y and 1p36. In 4 of 6 diploid tongue tumors, chromosomal aberrations were detected. Community of abnormalities was not found. All of 14 diploid thyroid carcinomas showed no chromosomal abnormality. In 7 tongue and 2 thyroid aneuploid tumors, increasing of number of chromosomes were detected frequently and most of them were tetrasomy. This indicated these abnormalities arisedafter tetraplidization. Disomy 1 and 11 were found remarkbly in some aneuploid tumors. To investigate the origin of disomy 1 and 11 in aneuploid tumors, we detected the differences between earlier chromosomal changes already presented in diploid component and later changes in aneupoid component after tetraploidization. It was necessary to correlate nuclear DNA content and FISH signals directly in each nucleus using a cytofluorometer epuiped with auto-scanning stage system. The origins of disomy 1 and 11 were thought to be either from tetrasomy cells through repeated loss of chromosomes after tetraploidization nor from monosomy cells through genome duplication. The results of double-target FISH also showed loss of 1p36 was worthy of note. In conclusion, loss of one of the 2 copies of chromosome 1, 11 and 1p36 in diploid tumor may play an important role in the emrgence and progression of aneuploid tumor.

View full abstract

E-cadherin is one of cell-cell adhesion molecules and is thought to play an important role in the mechanism of tumor metastasis. In this work, significance of E-cadherin in the metastasis of head and neck cancer was studied using animal models and clinical samples. When human cancer cell lines derived from E-cadherin-positive differentiated maxillary carcinoma were treated with anti-E-cadherin antibody, SHE78-7, showed enhanced invasiveness into the reconstructed basement membrane in invasion assay, and promoted metastasis in nude mice. Our results indicated that suppression of E-cadherin function promoted invasiveness and metastatic capacity of carcinoma cells. Suppressed E-cadherin function may be associated with 1) an increase of cell motility by loss of intercellular connection, 2) an elevation of proteolytic activity by stimulating matrix metalloproteinase (MMP-2) and tissue type plasminogen activator (t-PA), 3) an induction of angiogenesis by releasing vascular endothelial growth factor (VEGF).
For clinical aspect of E-cadherin, immunohistochemical examination showed that reduced E-cadherin immunoreactivity was associated with poor prognosis. Soluble fragments of E-cadherin (sE-cadherin) was examined by ELISA in sera of patients with head and neck cancer, malignant lymphoma, benign diseases, and healthy volunteers. sE-cadherin was significantly elevated in patients with head and neck cancer, and decreased after the successful treatment. In addition, increased level of sE-cadherin was observed in head and neck cancer patients with locaregional recurrence.
We conclude that the function of E-cadherin is closely correlated with invasiveness and metastasis, and may be of diagnostic importance for monitoring tumor progression.

View full abstract

For the purpose of achieving individually effective chemotherapy against head and neck cancers, the chemosensitivity was determined by using the intracellular ATP analysis (ATP assay).
The evaluable rate of ATP assay was 94%. The positive evaluation of this assay was defined as more than 50% depletion of the intracellular ATP contents, compared with the non treatment tumors. The positive rates were 5-FU 26.5%, CDDP 24.2%, CBDCA 24.2%, MTX 22.9%, PEP 22.7%, ADM 22.5%, and MMC 19.7%, respectively. In squamous cell carcinomas, the positive rates of 5-FU and CDDP were high compared with the other antitumor drugs. And the positive rates were high in the specimens derived from oral cavity tumors and mesopharyngeal tumors compared with the other anatomical sites.
Also fifteen clinical trials according to the results of ATP assay were evaluated prospectively and retospectively. The true positive rate was 75% and the true negative rate was 100%. Overall accuracy of this assay was 87%. From these results, it is suggested that ATP assay is useful in determining the chemosensitivities of head and neck cancers and performing the individual chemotherapy.

View full abstract

SDI test were carried out for 55 head and neck cancers (74 specimens), including 51 squamous cell carcinomas, two adenocarcinomas and two undifferenciated carcinomas, to assess the drug sensitivity of the tumor. As a result, the evaluable rate of SDI test was 80.0% (44/55). Cancer cells from the involved cervical lymph nodes showed a tendency of a low calculated Inhibition Index (I. I.) as compared with those of primary tumors. The in-vitro results were compared with the clinical responses of the 9 recurred patients who were treated by combination chemotherapy (5FU+CDDP). The following results were obtained for CDDP and 5FU (the positive evaluation of this assay was defined as more than 40% of I.I.): true positive rate, 25% (CDDP) and 33% (5FU); true negative rate, 80% (CDDP and 5FU); and predictive accuracy, 56% (CDDP) and 62.5% (5FU). Therefore, the SDI test might serve as a tool for the selection of non-effective chemotherapy in patients with head and neck cancer.

View full abstract

Multicellular tumor spheroids (MTS) have certain characteristics similar de novo solid tumors. They contain such extracellular matrix as fibronectin, laminin, collagen and hyaluronic acid, comprise a chronically hypoxic cell population in core and show heterogeneous cell cycle times. Comparison of the three-dimensional culture methods (MTS) with two-dimensional culture methods (monolayer) has shown differences in the behavior of chemotherapeutic drug responses. Generally, monolayer culture methods are over estimate drug responses. Practical applications of MTS is significant for drug sensitivity test. Biopsy material from human head and neck squamous cell carcinoma was cut with scalpels into pieces less than 0.5mm in diameter and maintained in agar plate by liquid overlay culture technique. A head and neck tumor is composed not only of tumor cells, but also of normal mesenchymal, endothelial, lymphocyte, macrophages and fibroblast. Therefore heterogeneous cultures of tumor cells, currently used for chemosensitivity test should be accurately model in situ tumor.
In this paper, we discussed the merit and demerit of chemosensitivity testing using MTS.

View full abstract

The chemosensitivity for head and neck tumor in our department (1985-1993) was evaluated by the two methods of subrenal capsule, which were tumor growth inhibition rate (TGIR) and inhibition rate of specific activity of succinate dehydroge nase (SSDI). 100 cases were carried out by measuring tumor size and 67 cases were new method. Furthermore the clinical correlativity was evaluated about 44 cases of oral malignant tumor by these two methods.
These two methods showed high evaluability (94%), SSDI method reflected the positive rate of clinical response.
The clinical correlativity of normal SRCA was low value (59.1%) and SSDI showed 74.2%.

View full abstract

To improve clinical results of cancer chemotherapy, it is important to select the most effsctive anti-cancer drug among many agents based on chemosensitivity test in each patient. We described in this paper, history, classification, and charachteristics of each sensitivity test. We also stated the outline and clinical usefullness of the succinate dehydrogenase inhibition (SDI) test that we have introduced in our institute as a clinical chemosensitivity test since 1984. The SDI test is a useful chemosensitivity test of clinical tumor specimens, since it is rapid, inexpensive, reliable, and convenient so that it has now been widely employed. To date, we have had data of clinical results with regard to SDI test against 4649 specimens from various human tumors. The data indicated that the chemosensitivity might be related to several factord such as histology, defferentiation, cell proliferative activity, intracellular enzyme concerning DNA synthesis, DNA ploidy pattern, and hormone receptor, and so on. We also found that the clinical results of chemotherapy were well correlated with the chemosensitivity by SDI test. We concluded that further improvement of clinical results of chemotyerapy for various human cancer will be brought in accordance with the progress of in vitro chemosensitivity test in future.

View full abstract

Hyperfractonation radiotherapy has been originally proposed based on the differential repair capacity of cells between early responding and late responding normal tissues to radiation. Clinical effectiveness of hyperfractionation has been evaluated in the phase III rondomized prospective trial in EORTC which showed a significant improvement in local control at 5 years for head and neck cancers.
Accelerated repopulation of tumor stem cells during radiotherapy had been predicted for head and neck aquamous cell carcinomas as shown by a short potential doubling time compared to usually a longer volume doubling time. This was a basis for the accelerated fractionation and was further supported by the evidence that tumor control dose in head and neck cancers increased with increase in the overall treatment time. Recent several clinical reports showed that improvement of patients survival could be obtained by accelerated hyperfractionation for tumors with a short potential doubling time.
Mathematical model describing effectiveness of altered fractionation roughly predicts clinical outcome of tumor and normal tissue response when incorporating corrections for incomplete repair and accelerated repopulation. However, individual variation in potential doubling time of tumors and in factors affecting late normal tissue reaction such as hyertension, arteriosclerosis and diabetes seems significant and important for furhher study.

View full abstract

The present status of clinical trial on multiple fractions per day (MFD) for head and neck tumors was reviewed and the problems and utility were discussed. The analysis of several phase I/II studies except a clinical trial of HFX, revealed, 1) significant improvement in local control, 2) statistically significant tendency or borderline significance in most studies concerning survival, 3) more severe acute reaction compared with CF and 4) the same reaction as CF, or weaker in Type A (CHART) concerning late injury. In conclusion, MFD is expected useful to improve the therapeutic ratio, although the effect on survival period is not clear. At present randomized phase III study on Type A is on going in England, also clinical trials including Type B, Type C and CF are on going in the US (RTOG). In the near future we will be able to obtain the final conclusion about the utility of MFD from these phase III trials. Only if the results are coclusive! If not, then there won't be a “final conclusion”!!

View full abstract

To improve the local control rate in radiotherapy for hand and neck cancer, several prospected twice-a-day fractionated tradiotherapy (TDRF) were conducted in Tokyo Women's Medical College. [I] T2 glottic cancer was irradiated with 1.5Gy/fraction, 2 fraction/day to a total dose of 72Gy. Five cumulative local control rate was 88.2%, [II] Locally advanced head and neck cancer was treated with TDFR and systemic chemotherapy. Response rate was 100%. [III] Palliative radiotherapy with TDFR was done to relive from the pain and other symptoms for advanced and recurrent cases. Nine cases of 11 were relieved from the symptoms. These results was suggested the TDFR was usefull to improve the local contro rate.

View full abstract