PCNA (proliferating cell nuclear antigen) is a 36 KD polypeptide that is maximally expressed in late G1 and S phases of the cell cycle, and correlates with DNA synthesis. Although the rates of proliferating tumor cells have been reported to be a marker for the malignant potential of several tumors, the clinical significance of proliferative activity in oral malignancies has not yet been fully investigated. This article presents the results of an immunohistological analysis of 22 squamous cell carcinomas of the tongue using anti-PCNA monoclonal antibody. The rate of PCNA positive cells was significantly related to clinical stage (p<0.05), histological grade (p<0.05), mode of invasion (p<0.05) and DNA ploidy (p<0.05). The percentage of PCNA positive cells was higher in cases with recurrence of the primary lesion than in cases without recurrence, although the difference was not statistically significant. On the other hand, a positive relationship was observed between the rate of PCNA positive cells and the incidence of cervical lymph node metastasis (p<0.05), with the incidence of lymph node metastasis being significantly (p<0.01) higher in cases with more than 30% PCNA positive cells than in those with less than 30% positive cells. In addition, the cumulative 3-years survival rate was significantly (p<0.01) worse in cases with more than 30% positive cells than in those with less than 30% positive cells. These results suggest that the rate of PCNA positive cells can be utilized as a diagnostic parameter which predicts the propensity for cervical lymph node metastasis and the prognosis in squamous cell carcinomas of the tongue.
In 127 cases of oral cancer, the serum tumor marker levels, and in a portion of the cases, the localization of tumor markers within the tissue were examined. The results were as follows: 1. There was a propensity for the serum SCC levels prior to treatment to be elevated with increasing tumor size as well as with progression in stage. 2. The serum IAP and SCC levels prior to treatment were significantly higher in secondary cases than in primary cases, indicating that elevated levels were related to recurrence. 3. In our department, groups with recurrence following primary treatment showed significantly higher SCC levels prior to treatment as compared to the groups without recurrence. 4. The serum IAP levels dropped significantly following preoperative therapy with a combination of chemotherapy, radiation and hyperthermia. Measurement of these levels was useful for evaluating the effectiveness of chemotherapy, radiation therapy and hyperthermia. 5. In cases showing recurrence after operative therapy, there was a statistically significant elevation in IAP levels as compared to preoperative levels 6 months and 1 year postoperatively. There was also an elevation in SCC levels 3 months postoperatively. 6. Compared to the group without recurrence, the group with recurrence had significantly higher IAP levels at 3 and 6 months, and higher levels at 3 months postoperatively. 7. Recurrence is suspected in cases with high elevations of IAP and SCC levels 3 and 6 months postoperatively. 8. Upon immunohistological staining, IAP and CEA reacted strongly with tumor cells, indicating the border of tumor cell infiltration. 9. CEA was found in the central area of the cancer pearl. IAP was found in the surrounding regions with high cancer activity. This suggests the high sensitivity of serum IAP. These results indicate that serum tumor marker levels and intra-tissue tumor markers are useful for asessing the pathological status, selecting the method of treatment, evaluating the effectiveness of treatment, and determining the prognosis in oral cancer.
Progressive resorption of the alveolar ridge after tooth extraction results in diminished retention and stability of a denture. Preprosthetic augumentation of the alveolar ridge is therefore required to provide a firm base for a denture and reconstruct the functional occlusion in the field of oral and maxillofacial surgery. Octacalcium phosphate (OCP), the putative precursor of biological hydroxyapatite, was implanted into the subperiosteal pocket adjacent to the mandibular alveolar ridge in 7-week-old male Wistar rats. Soft radiographic and the histological examinations were performed to investigate the biological response to the OCP implant and assess possibilities for the clinical application. OCP was prepared using the method of LeGeros; granules between 32 and 48 mesh were used for implantation. Four rats were used in each experimental group. The animals were perfused with 4% paraformaldehyde in 0.1 M phosphate buffer at pH 7.4. After soft radiographic examination, the specimens were decalcified in a mixed solution of sodium citrate and formic acid, embedded in paraffin, sliced into thin sections, and stained with hematoxylin and eosin. In the experimental group, signs of radiopacity were not obvious at the implantation site at one week. At two weeks, increased signs of radiopacity were noted at the implantation site. The radiopacity increased markedly by four weeks after implantation and seemed to be relatively homogeneous, well amalgamated to the contiguous bone. Bone resorption was not obvious at the implantation site after eight weeks. Histologically, the implanted-OCP (i-OCP) was stained by hematoxylin at one week. The ridge was augumented at the region corresponding to the implantation site. Numerous connective tissue cells and inflammatory cells were surrounding i-OCP. Additional bone formation increased with time. I-OCP tended to aggregate and be resorbed. Two weeks after implantation, inflammatory cells decreased. After four weeks, i-OCP was surrounded by new bone. The newly formed bone was observed to mature with time and was not resorbed after eight weeks. The present study suggested that OCP is a useful material to augument the atrophic alveolar ridge in preprosthetic surgery.
Recently, artifical biologic materials have been extensively applied for clinical treatment but chronological follow-ups have rarely been reported. At present, chronological evaluations are made with X-ray photos and computed tomography. There for, detailed observations of changes in artificial biologic materials have been difficult. Here we clinically employed these materials and determined the time course of minute changes in bone tissue by X-ray image analysis systems.
Osseointegrated implants are currently recognized to be effective when used in preprosthetic surgery. Simultaneous bone grafting procedures to treat severely atrophic maxillae has, however, been little reported. Surgical procedures vary depending on the site and extent of bone resorption and bone quality; therefore, surgical planning should be carefully executed. We have simultaneously placed osseointegrated implants in conjunction with bone grafting in 9 of 10 extremely absorbed maxillae. In this report, the clinical course of alveolar bone resorption around the fixtures, survival rate of the installed fixtures, and masticatory efficiency in relation to surgical procedure were discussed. 1. The patients consisted of nine females and one male, ranging in age from 16 to 58 years. 2. A total of 59 fixtures were placed. In totally edentulous cases, six to eight fixtures were placed. In partially edentulous cases, two to five fixtures were placed. Four fixtures failed to achieve osseouintegration. Mean overall survival rate was 93.2% for a 1.5 year followup period. 3. The degree of bone resorption was 0.6 mm in 6 months, and 1.0 mm in one year after initial surgery. After the first year, bone resorption rate is stabilized at 0.2 mm per year. 4. Regarding masticatory efficiency assessed pre-and post operatively, all of the cases showed extreme improvement. The mean masticatory score in totally edentulous cases was 32 points preoperative and 92.5 points postoperative; that in partial edentulous cases was 44 points preoperative and 97.5 postoperative. These results indicate that osseointegrated implants in conjunction with bone grafting is a satisfactory procedure to restore masticatory function in patients with extreme atrophic maxillae.
We investigated the changes of signs and symptoms in 18 cases suffering from persistent closed lock. The results were as follows: 1. Severe pain was present in all patients at the beginning of treatment. At the end of treatment, severe pain was noted in only one patient. Pain disappeared or improved in the other patients. Continued improvement was found during follow-up. 2. Average maximum mouth opening was increased from 25.2 mm to 35.3 mm after conservative treatment. This trend also continued during follow-up (ave. 37.3 mm). 3. Crepitation was noted in 44.4% of the patients at first visit. It increased during conservative treatment, and was noted in 77.8% at the end of treatment. However, crepitation decreased, and was recognized in 55. 6% during follow-up. 4. The incidence of radiographic bone changes (erosion, osteophytes and/or deformity) of the condylar head was 66.7% initially and increased during treatment and follow-up. 5. These results indicate that severe pain and trismus in these patients improved to some degree by long-term conservative treatment, but prolonged careful follow-up is required in persistent cases, especially those with bone changes and/or crepitation.
Clinicopathological features associated with secondary cervical lymph node metastases (SLM) of squamous cell carcinomas of the head and neck were investigated. SLM were found in 27 (17. 2%) of 157 TXNO head and neck carcinoma cases from November 1975 to June 1991. The most common primary site was the tongue (21 cases), and approximately 80% of SLM occurred within one year after primary treatment; this period was therefore felt to be the most appropriate for follow-up. The five-year cumulative survival rate for SLM cases was 40. 7%. Reasons for decreased survival in these cases included the following: 1. Tumors in metastatic nodes were histologically more invasive than those in the primary site. 2. Multiple metastases to cervical lymph nodes were present. 3. Spreading to multiple levels of the cervical lymph node chains had occurred. 4. Extra-nodal spread and metastases to distant cervical levels were observed in many cases. Extra-nodal spread, the number of positive nodes and the level of positive nodes were the most important prognostic factors in SLM cases. No factor predicted which patients were more likely to have SLM in tongue carcinoma. Thus, there were no absolute indications for elective neck dissection (END). END should, however, be considered in carcinomas showing diffuse invasive (grade 4C and 4D) or endophytic growth types or those cases where invasion of the floor of the mouth, retromolar region and base of the tongue is present.
The immunohistochemical staining of p53 was detected not only in squamous cell carcinoma but also in normal stratified epithelium. The immunostaining of p53 and PCNA was localized in similar areas of cancer tissue. The number of positive cells was counted using image analysis system PIAS LA 555. PCNA and p53 positive rates were 74.0%(108/146) and 22.6%(33/146), respectively. PCNA and p53 scores were 34.6 ± 2.4%(n=108) and 26.8 ± 4. 1%(n=33) as mean ± SE. Flow cytometrical analysis revealed 20 cases of diploidy and 6 cases of aneuploidy among 146 cases of squamous cell carcinomas. PCNA score was 49.9 ± 5.2%(n=16) in diploidy and 37.5 ± 13.8%(n=5) in aneuploidy. p 53 score was 35.6 ± 12.6%(n=5) in diploidy, and 25.9 ± 16.5%(n=2) in aneuploidy. These results suggested similarities in immunostaining between p53 and PCNA, and that p 53 score was smaller than PCNA score. Further investigation is required to clarify the relationship between p53 and DNA ploidy pattern.
Natural killer (NK) cell activity of OK-432-stimulated peripheral blood mononuclear cells (PBMC) was examined. Low concentrations of exogenously added recombinant interleukin 2 (rIL-2) were able to augment OK-432-induced NK cell activity. This kind of augmenting effect depended on the dose of rIL-2 and manifested itself only in PBMC stimulated with OK-432 (OK-MC) followed by rIL-2; augmentation did not happen when drugs were applied in the reverse order. The existence of CD16+ /CD25+ (IL-2 receptor positive; IL-2R+) and CD57+ /CD25+ double positive cells which possess NK cell surface markers in OK-MC markedly increased in a long-term culture (12 days). A strong positive correlation was observed between the IL-2-dependent augmentation of NK activity and the quantitative changes in cell populations that possessed NK cell phenotypes. Furthermore, this augmenting effect was detectable within 4 h after addition of rIL-2 at single cell level, suggesting that the effect did not require NK cell's DNA synthesis. Thus, the use of OK-432 activated NK cells in combination with IL-2 in clinical trials is expected to afford high efficiency in cancer immunotherapy.
We analyzed 10 maxillary ameloblastomas clinicostatistically for the past 23 years from 1970 to 1992. The incidence of maxillary ameloblastoma was 6. 5% of all ameloblastomas in the jaw bones. Age at the initial visit was the fifth decade or over in eight patients. Many tumors extended from the anterior or premolar to molar region and 6 cases involved the maxillary antrum. There was no case with an embedded tooth in the tumor. Radiographically, unilocular and multilocular radiolucency was seen in the majority of cases. Histologically, follicular type was seen in six cases, basal cell ameloblastoma in 3, and desmoplastic ameloblastoma in 1. Two cases of follicular type and 1 of basal cell ameloblastoma were malignant ameloblastomas. Recurrence was noted in 2 of the cases; both of these 2 cases were malignant ameloblastomas.
In this paper, we report a case of maxillary osteosarcoma which was suspected to be radiation-induced cancer. The patient, a 67-year-old male, received 35 Gy of 60Co external beam, 2, 000 mg of 5-FU via the superficial temporal artery and an antrostomy at another hospital in 1977. In, 1986, nine years after the radiotherapy, a maxillary osteosarcoma arose in the irradiated field. The possibility of radiation-induced osteosarcoma is very high, because the tumor is categorized into group A of Sakai, et al. definition of induced cancer. Gastric cancer was also concurrently present. In spite of the operation, he died of recurrent gastric cancer and liver metastasis. It was suggested that double cancers involving the gastrointestinal system should be surveyed in cases of head and neck cancer.
The authors report three cases of unilateral soft palate hypoplasia without any other major malformations. Case 1: A 9-year-old boy had a left velar defect, which consisted of unilateral hypoplasia of the levator palatini, the tensor palatini, palatoglossus, and the palatopharyngeus muscles. He manifested no signs of velopharyngeal incompetence before the age of 7 years. However, mild rhinolalia appeared at 7 years old. No articulatory disorders were found. Case 2: A 3-year-old girl had similar findings on the left side and a hamartoma at the base of the tongue. Velopharyngeal incompetence had not been manifested yet. She is under follow-up. Case 3: A 9-year-old girl had similar findings on the right side. No velopharyngeal incompetence has been manifested.
Cancer occuring in the dorsum of the tongue is very rare. Several reports indicate that the rate of cancer occurrence in the dorsal tongue ranges from 2.8% to 7.2 % of all tongue cancer. In our clinic, there has been only one case of dorsal tongue cancer among 89 cases of tongue cancer from 1979 to 1992. The patient was a 68-year-old male who visited our clinic with a chief complaint of a tumor mass in the left dorsum of the tongue in November 1983. The tumor was a round, circumscribed, raised, and centrally depressed mass with a red surface. It was 15 mm in diameter and elastic but firm in consistency. Macroscopically, the tumor was doughnut-shaped. Pathologically, the tumor was diagnosed to be a squamous cell carcinoma. He was treated by intraoral electron therapy, one time (10 Gy) per week. The total dose amounted to 40 Gy. Clinically and pathologically, the tumor disappeared at that time. Nine years after intraoral electron therapy, he is still alive without primary recurrence or distant metastasis.
We report a case where Kaposi's sarcoma was seen in the hard palate of a patient with AIDS. Kaposi's sarcoma could be controlled by radiotherapy. During follow-up, no other oral changes were found. There have been few Japanese patients with Kaposi's sarcoma in our hospital. Only one patient has died due to Kaposi's srcoma of the lung.
We presented two cases of calcifying epithelioma in the parotid-masseteric region. One was a 59-year-old woman, and the other was a 38-year-old man. Both cases had been aware of persistent subcutaneous nodules in the region for about thirty years. The nodules were painless, well-defined, movable and firm. A clinical diagnosis of calcifying epithelioma was made and the tumors were enucleated. There was minimal adherence between the tumors and the surrounding tissues. The enucleated tumors measured 28 × 17 × 7 mm and 20 × 13 × 7 mm, respectively. Histopathologically, they were composed of distinctly bordered nests or masses of shadow cells which possessed a central unstained area due to nuclear loss. Few basophilic cells and large areas of calcification were observed. In part of the tumors, a little bone formation was also observed. The postoperative progress of the two patients is satisfactory without recurrence.
Angiofibroma is a rare type of benign tumor. It mostly occurs in the nasopharyngeal area of juvenile males. A huge angiofibroma in the right cheek of a 76-year-old female is described. The tumor was removed under local anesthesia with an intraoral approach. It measured 70×85 mm and weighed 150 g. The histopathological diagnosis was angiofibroma. Her progress has been favorable 23 months after the operation.
A 3-year-old boy was referred to our clinic with swelling of the neck, submandibular region and tongue. The patient had been previously treated in our clinic with local injection of bleomycin. We therefore resected the neck tumor and performed tongue reduction. After the operation, the patient was applied a chin-cap to manage progenia and open bite which were caused by congenital swelling of the tongue. Application of the chin-cap for 3 years brought about cure of the progenia and open bite. At the age of 7 years and 6 months, a huge cystic lymphangioma appeared in the parapharyngeal space. MRI was very effective in allowing us to estimate the characteristics of this cystic lymphangioma of the parapharyngeal space. Fortunately, OK-432 local injection therapy was effective for the lymphangioma, and no recurrence has been noted for 2 years and 3 months.
We report a case of neurofibroma that was considered to be a solitary lesion at the left submandibular region. A 44-year-old female patient complained of swelling at the left submandibular region. Her physique and nutritive status were good and there were no signs of dermal abnormalities. An elastic hard tumor, the size of the tip of the forefinger was detected by paplation at the left submandibular region. The clinical diagnosis was a benign tumor of the left submandibular region. The tumor was surgically resected under local anesthesia. The result of histopathological examination was neurofibroma. Although almost one year has passed since the operation, there has been no evidence of recurrence.
A 49-year old female with palatal perforation due to congenital syphilis is reported. She was diagnosed on the basis of clinical, serological and epidemiological features. Clinical examination showed a ‘Saddle nose’ deformity, and ‘palatal perforation’. Her clinical course was as follows: Her hard palate perforated at the at the age of 10 years. At the age of 16, a fistula closure operation was executed, but soon after the operation perforation of the hard palate recurred. At the age of 37, she lost all teeth of the upper jaw. She has been using a complete denture of the upper jaw since age 41. She recently felt uneasiness with the denture, probably due to thinning of the bone around the premaxilla. She therefore visited our clinic through the introduction of a dental practitioner for examination of the palatal perforation. Her disease history was unnoteworthy. Her laboratory data were all within the normal except for a positive TPHA reaction. Her father was treated for syphilis before her birth. Due to advances in treatment against syphilis, progressively fewer cases of syphilis are encountered. Late congenital syphilis has become particularly rare recently.