Graft-versus-host Disease-free, Relapse-free Survival After HLA-identical Sibling Peripheral Blood Stem Cell Transplantation With Tacrolimus-based Graft-versus-host Disease Prophylaxis in Japanese Patients.

The ideal post-allogeneic hematopoietic cell transplantation recovery is not just the cure of hematologic malignancies but also freedom from ongoing morbidity. Recent studies have revealed that HLA-identical sibling peripheral blood stem cell transplantation (PBSCT) had been providing impaired graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) due to a higher risk of GVHD. Study on GVHD prophylaxis bears clinical reliance when focused on Japanese population because risk of GVHD differs among races. We identified 15 consecutive Japanese patients who received tacrolimus-based GVHD prophylaxis after myeloablative HLA-identical sibling PBSCT. No episode of grade ≥ II acute GVHD and only one episode of grade III toxicity were documented, with the control of mean weekly blood tacrolimus concentrations during the first 4 weeks at 13 to 17 ng/mL. An estimated 46.7% (95% CI: 21.4% to 71.9%) of the patients enjoyed their GRFS at 3 years after transplantation, and failure in the treatment of chronic GVHD was not reported during the median follow-up period of 1059 days (range, 784 to 1778 days) after the development of chronic GVHD. The results suggest that the application of tacrolimus with the optimization of its blood concentrations may effectively prevent ongoing morbidities after HLA-identical sibling PBSCT.

The lingual lymph node identified as a sentinel node on CT lymphography in a patient with cN0 squamous cell carcinoma of the tongue.

We performed CT lymphography on an 81-year-old female patient with a histologically confirmed squamous cell carcinoma of the tongue with no clinical or radiological evidence of cervical lymph node involvement. The lateral lingual lymph node was identified as a sentinel node, which is the first lymph node to receive drainage from a primary tumour. CT lymphography also showed draining lymphatics passing through the sublingual space, the medial side of the submandibular gland and near the hyoid bone and connected with the middle internal jugular node. Although metastasis to the lateral lingual lymph node is known as one of the crucial events in determining survival outcome in cancer of the tongue and floor of the mouth, very few reports are available on the imaging of the lateral lingual lymph node metastasis. This is the first report regarding the lateral lingual lymph node identified as a sentinel node demonstrated on CT lymphography.

Clinical significance and usefulness of quantification of telomerase activity in oral malignant and nonmalignant lesions.

We quantified telomerase activity (TA) in patients with oral and maxillofacial malignant and nonmalignant lesions, and compared it with their clinical status and grade of malignancy. Fifty-two malignant and 52 nonmalignant lesions were analyzed. All malignant lesions were pathologically diagnosed as oral squamous cell carcinoma (OSCC). Normal gingival tissue served as a control. These specimens were obtained by biopsy or surgical resection, and stored at -80 degrees C until use. TA was quantified by a fluorescence-based TRAP method. TA levels ranged from 0.00 to 95.24 (average 33.24)U/microgP in 52 malignant lesions, and from 0.00 to 79.35 (average 11.91)U/microgP in 52 nonmalignant lesions (P < 0.0001). TA was detected in 96.2% of malignant and 65.4% of nonmalignant lesions. There was no relationship between TA levels and clinical stages or YK classification. However, under WHO classification, there were significant differences (P < 0.05) between Grades I and III or II + III. Among nonmalignant lesions, epithelial dysplasia showed a significantly higher TA level than that of oral lichen planus (P < 0.05) and other benign lesions (P < 0.0001). Oral lichen planus also significantly differed from other benign lesions (P < 0.05). These results suggest that TA is related to the histological grade of malignancy, and is also useful as a prognostic predictor for precancerous lesions and conditions.

Malignant melanoma of mandibular gingiva; the usefulness of fat-saturated MRI.

Case report of a histologically validated malignant melanoma affecting the mandibular molar gingiva in a 31-year-old woman. Tumour was evaluated by magnetic resonance (MR) imaging at 1.5-T, spin-echo 3 mm slice thickness with T1-weighted and fat-saturated T1-weighted images. The fat-saturated T1-weighted images demonstrated the lesion more clearly than conventional T1-weighted images.

Changes in masticatory function after orthognathic treatment in patients with mandibular prognathism.

Changes in masticatory function were measured in 27 patients in whom mandibular prognathism was corrected surgically. The mean value of masticatory efficiency before treatment was 46% of that of control subjects with normal occlusion. It improved, but remained at 60% of the control value postoperatively. Similar changes were seen in the number and area of occlusal contacts and the integrated muscle activities of the masseter and temporalis on the chewing side, but the postoperative improvement in masticatory efficiency was mainly the result of improvement in masseter activity. The mean values of masticatory cycle variables in the patient group did not differ significantly from those of the controls. Their preoperative mean coefficients of variation, which were significantly higher than those of the controls, decreased significantly postoperatively. These results suggest that the stability of masticatory rhythm was improved by orthognathic surgery.

The impact of extranodal spread of lymph node metastases in patients with oral cancer.

A retrospective study of 61 patients with histologically confirmed lymph node metastases was undertaken to evaluate the prognostic significance of extranodal spread (ENS) of metastases on the patterns of treatment failure and survival. ENS was present in 28 (46%) of the 61 patients and it was significantly associated with N stage. T stage, clinical stage, number of positive nodes, level of metastases, mode of treatment, and histological differentiation, however, did not influence the incidence of ENS. The 5-year disease-specific survival rate was 57%. The values for patients with and without ENS were 40% and 72%, respectively, which were statistically significant. The univariate analysis showed that the presence of ENS was a significant predictor of patient survival (P = 0.008). The number and level of positive nodes and postoperative radiotherapy had no prognostic importance. ENS, however, was also associated with an increased risk of distant metastases.

Temporomandibular joint symptoms and disc displacement in patients with mandibular prognathism.

Our objective was to find out the incidence of signs and symptoms of temporomandibular joint (TMJ) and disc displacement in patients with mandibular prognathism. Fifty-one patients were examined clinically and by axial computed tomography(CT). The incidence of TMJ signs and symptoms was 6/25(24%) in patients with simple mandibular prognathism and 12/26(46%) in patients with mandibular prognathism and asymmetry. No discs were displaced in patients with simple mandibular prognathism, but 15(58%) of the patients with mandibular prognathism and asymmetry had displaced discs. There was no association between signs and symptoms of TMJ and disc displacement. Patients with mild protrusion and severe asymmetry of the mandible had a high incidence of disc displacement, which interestingly was on the deviated side in 14 of the 15 patients affected. We conclude that skeletal morphology may have a role in the development of TMJ disorders but the mechanism is obscure.

Oral carcinomas detected after extraction of teeth: a clinical and radiographic analysis of 32 cases with special reference to metastasis and survival.

A study was performed of 32 oral carcinomas that were diagnosed after recent dental extraction with particular reference to metastasis and survival. Eighty-four per cent of the patients complained of local swelling and/or pain. Infection had been suspected in 74% of the patients by the referring doctors. The involved teeth had been extracted in all patients. Ulceration and granulomatous tissue suggestive of carcinoma were found in the extraction sites in 24 patients when they were referred to us. Radiographs at presentation, available in 26 patients, showed diffuse radiolucencies with irregular borders around the extraction sites. Tumor or carcinoma were the clinical diagnoses in 27 patients. All patients underwent chemotherapy, irradiation and/or surgery, or a combination of these with curative intent after the diagnosis was confirmed histologically. Compared to a group of patients in whom dental extraction was not performed, the incidence of pathologically positive lymph nodes was significantly higher in the extraction group (52% vs 26%). The five-year survival in the extraction group was also lower (35% vs 48%).

Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological variables.

We analysed 32 primary, 8 recurrent and 16 metastatic squamous cell carcinomas of the head and neck by flow cytometry to assess tumoural heterogeneity. Intratumoural heterogeneity was found in 9 of 30 primary tumours (30%). All heterogeneous tumours had diploid and aneuploid cell lines. DNA indices were different from those of the primary tumours in 3 of the 8 recurrent lesions (38%) and in 8 of the 12 metastatic lesions (67%). The results indicate that new cell lines evolve during the process of recurrence and metastasis. The incidence of recurrence, metastasis, and heterogeneity increased with the size of the tumour. Histologically, there were tumours in which the degree of differentiation and mode of invasion of primary lesions were not consistent with the results of flow cytometry in both homogeneous and heterogeneous tumours. In conclusion, multiple sampling for flow cytometric analysis is essential for better characterization of oral carcinomas.

Current evaluation of dental implants: a review of the literature.

The literature concerning the success rates and the causes of failure of dental implants is reviewed in this paper, and the factors influencing clinical outcome are discussed. Most dental implants seem to be clinically acceptable during the first few years of installation, as long as the initial healing is uncomplicated. On a long-term basis, however, osseointegrated implants are the most reliable among those currently available for routine use. The lack of sufficient scientific data and well-controlled clinical studies with adequate criteria for assessing successful outcome are the main reasons why most other dental implants cannot be clinically recommended without criticism.

Predicting factors for distant metastases in head and neck carcinomas: an analysis of 103 patients with locoregional control.

PURPOSE: This study evaluated the ability of certain clinical and pathologic parameters to predict distant metastases (DMs) in patients with squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: A total of 103 patients with histologically proven squamous cell carcinoma of the head and neck were studied. None had persistent or recurrent disease above the clavicle. Of these patients, 48 (47%) had metastatic lymph nodes. The relationships of tumor stage, primary site, clinical growth pattern, tumor differentiation, regional node status, and extranodal spread (ENS) with DMs were evaluated. RESULTS: Twenty-one (20%) of the 103 patients developed DMs as the initial treatment failure. The incidence of DMs was significantly higher in patients with neck metastases (40%) than in those without neck metastases (4%) (P < .001). The degree of histologic differentiation and the presence of ENS were also correlated with the subsequent occurrence of DMs. There was no statistical difference in the incidence of DMs based on sex, location, stage of the disease, and clinical growth pattern. On multivariate analysis, only pathologic nodal status and ENS proved to be independent cofactors of DMs. The most common site of DMs was the lungs (56%), followed by bone (16%) and skin (16%). CONCLUSION: The presence of pathologically positive nodes is the most critical factor to influence the eventual development of DMs.

The implication of DNA content and S-phase fraction in oral carcinomas with and without metastasis.

Flow cytometry DNA analysis was performed on fresh tissue samples of 90 primary lesions and 32 metastatic lymph nodes of squamous cell carcinomas of the oral cavity and related regions to elucidate the characteristics of tumors with metastatic potency. The incidence of aneuploidy for carcinomas with metastasis was 67%, which was significantly higher than the 44% of carcinomas without metastasis, and aneuploid carcinomas (39%) had a higher tendency to metastasis than diploid carcinomas (20%). The incidence of aneuploidy and metastasis was related to the T classification, the degree of differentiation, and the histologic grade of malignancy. The incidence of aneuploidy and mean DNA index of metastatic lesions were 31% and 1.12, respectively, and the values were significantly lower than the 67% and 1.30 of the corresponding primary lesions. The results indicate that the chance of evolution of metastatic cell lines is higher in aneuploid carcinomas than diploid carcinomas, possible because the former is more heterogeneous than the latter, but most of the cell lines causing lymph-node metastasis are diploid cell lines. Metastatic lesions had a lower S-phase fraction than primary lesions, indicating that a high S-phase fraction does not always reflect the presence of metastatic cell lines.

Surgical treatment of stage I and II oral squamous cell carcinomas: analysis of causes of failure.

Sixty-one patients with stage I and II squamous cell carcinomas of the oral cavity treated by surgery alone were analysed to investigate treatment outcome, pattern of failure, and occurrence of second malignant neoplasms. The disease recurred or developed lately in 11 patients. The ipsilateral neck was the most common site of failure. Salvage treatment was successful in only three of these patients. Occult neck metastasis was found in 31% of patients with T2 tumours. Second malignant neoplasms developed in 20 patients and were the cause of death in 8 patients. In conclusion, locoregional control of stage I and II oral carcinomas is achieved by surgery alone. Elective neck dissection is required for patients with stage II tumours, showing a high risk of lymph node metastasis in histology.

Computed tomographic evaluation of lymph node metastasis in head and neck carcinomas.

A retrospective study of 53 patients was undertaken to evaluate the efficacy of computer tomography (CT) in the detection of nodal metastases from carcinomas of the head and neck. The CT findings of 53 patients with head and neck carcinomas who underwent a total of 57 neck dissections were compared with the findings of physical examination (PE) and histopathological examination. Using node size larger than 10 mm in the short-axis diameter or the presence of central lucency as the criteria of nodal metastasis CT scanning staged correctly 52 of 57 necks, providing an accuracy of 91%, a sensitivity of 86% and a specificity of 100% in the detection of nodal metastases. There was agreement of PE findings with histology in 43 (74%) of 57 necks, with a sensitivity of 97% and a specificity of 38%, respectively. Because CT scanning was superior to PE in the pre-operative staging of head and neck carcinomas, it should be used for pre-operative evaluation of metastatic neck disease.

Histopathological study of lymphatic invasion in squamous cell carcinoma (O-1N) with high potential of lymph node metastasis.

The process of lymph node metastasis was studied in an animal model (termed O-1N) that was successfully established using a metastatic tumor to the submandibular lymph node from a chemically induced squamous cell carcinoma of the hamster tongue. The model has been maintained by serial transplantation of metastatic tumors into the buccal pouch. Lymphovascular invasion of transplanted O-1N in the tongue was examined in serial histologic sections. Lymphatic vessels were distinguished from blood vessels by Masson's trichrome stain for vascular smooth muscle, BSA-I lectin binding for vascular endothelium, and laminin and type IV collagen immunostaining for the vascular basement membrane. Transplanted tumors enlarged progressively with invasion of surrounding tissues of the tongue and resulted in lymph node metastasis in all animals with successful takes. Local growth of the tumors in the tongue was accompanied by stromal proliferation with abundant dilated lymphatic vessels which contained clusters of tumor cells. On serial sections, the carcinoma cell clusters in lymphatics in the close proximity of tumor nests were in continuity with adjacent tumor nests, whereas such continuity was not recognized in those occurring apart from tumor nests. The formation of isolated carcinoma cell clusters resulting from disintegration of elongated processes of tumor nests with invasion of lymphatics and subsequent transport in lymphatics and deposition in lymph nodes in clusters were well demonstrated in other serial sections. The key step of lymph node metastasis therefore appears to be direct invasion of lymphatic vessels by tumor cells, similar to their invasion of adjacent tissues but different from the way that blood cells escape through vessel walls. Proliferation of lymphatics around tumor nests and transport of tumor cells in clusters would also contribute to the production of metastatic deposits in lymph nodes.

Histologic study on the metastatic process in the experimental model of lymph node metastasis.

The process of lymph node metastasis was studied in an experimental model that was successfully established in our laboratory. The model O-1N carcinoma was transplanted to the buccal pouch of 60 hamsters, and seven or eight hamsters were killed every week from 1 to 8 weeks for histologic examination. At 3 weeks, neoplastic invasion of vascular spaces was demonstrated, and early stage lymph node metastases were seen in five of seven animals. At 5 weeks, lymph node metastases were more advanced, and lung metastasis occurred in one animal. At 8 weeks, lymph node metastases were seen in all eight animals and lung metastases were seen in two of them. Tumor cells initially seen as clusters in afferent lymphatic vessels and in the peripheral sinuses gradually spread to the medulla, replaced the entire lymph node, and extended into adjacent extranodal tissue. The process of metastasis closely resembled that seen in human oral carcinomas.

Chin augmentation with porous hydroxyapatite blocks.

The results of chin augmentation by porous hydroxyapatite blocks were evaluated clinically and radiographically in nine patients. Recovery of a satisfactory facial profile was achieved by the procedure, and all patients but one, with removal of the implant because of infection, were satisfied with the results of the surgery. Radiographically, the implants were incorporated into the bony structure of the mandible by deposition of bone at and around the bone-implant interface and ingrowth of bone into pores. Cephalometrically, the procedure was found to provide very stable results, with little change in the position of the implants and no appreciable resorption of the implants and bone. Despite heavy chemotherapy, histologic examination of the removed hydroxyapatite showed the presence of areas with numerous inflammatory cell infiltration and no bone formation. Thus, the procedure is quite useful for chin augmentation, but utmost care should be taken to avoid infection.

The role of radiotherapy in the management of salivary gland carcinomas.

A retrospective study was performed on 44 patients with carcinoma originating in the major and minor salivary glands to examine the effects of postoperative radiotherapy on locoregional and distant control and survival. 22 patients were treated by surgery alone and the 22 other patients were treated by a combination of surgery and postoperative irradiation. In the surgery group, local recurrence developed in all 8 patients with evidence of residual disease at the surgical margins, whereas local control was achieved in 7 of 15 patients with positive surgical margins in the combination group and the control rate was related to the amount of residual disease. Neck metastasis, which developed in 13 patients (30%), was not affected by the status of surgical margins or by the treatment modality. On the other hand, the incidence of distant metastasis seen in 19 patients (43%) was much higher in patients with positive surgical margins and the development of distant metastasis in these patients was not prevented by postoperative irradiation. The survival rates at 5, 10 and 15 years were 54, 48 and 41%, respectively, for the irradiated patients, whereas the values for the patients treated by surgery alone were 75, 70 and 70%, respectively. The results indicate that postoperative irradiation is effective in controlling local recurrence but not neck and distant metastases. Wide excision with sufficient surgical margins followed by postoperative radiotherapy and systemic chemotherapy are essential to obtain a better prognosis.

The value of single versus multiple sections for detection of lymph node metastasis.

This study was undertaken to determine the value of serial sectioning of lymph nodes as an aid in optimally examining cervical specimens for metastasis. The presence or absence of lymph node metastasis in 802 lymph nodes obtained from 51 consecutive neck dissection specimens were initially determined by the routine method, examination of one section from each node. This examination revealed 40 lymph nodes with metastatic involvement. Further study of the 716 lymph nodes that were initially interpreted as free of tumor by serial sectioning added only two positive nodes. Thus, serial sectioning did not contribute significantly to the detection of lymph node metastasis.