Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria.

PURPOSE: This study aimed to clarify the clinical utility of oral management to prevent bloodstream infections by oral bacteria microbiologically in patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT). METHODS: Ten consecutive patients with hematological malignancies undergoing ASCT were enrolled in this study. We implemented dental treatments before transplantation, if required, and carried out oral hygiene instructions and oral management every other day after transplantation. Molecular analysis of bacterial DNA for seven oral species using a polymerase chain reaction (PCR) assay was performed for oral samples and peripheral blood once a week for 3 weeks after transplantation. RESULTS: Periodontitis was found in all 10 patients (mild grade in 3 and middle grade in 7) for whom basic periodontal therapy was conducted. Necessary dental procedures, including tooth extraction were performed in 5 patients. After transplantation, oral mucositis occurred in 10 patients (grade 1 in 3, grade 2 in 2, and grade 3 in 5) for whom oral hygiene instruction and oral care were continued every other day. PCR-identified three to six bacterial species in oral samples from nine patients, but none in peripheral blood from any patient during the observation period. CONCLUSIONS: Our study suggests that oral management could prevent bloodstream infections by oral bacteria in ASCT recipients despite the existence of periodontitis or oral mucositis. Its utility was confirmed by microbiological evidence based on molecular data.

A comparison of two types of microcatheters used for a novel external carotid arterial sheath system for intra-arterial chemotherapy of head and neck cancer.

PURPOSE: We developed an external carotid arterial sheath (ECAS) for performing intra-arterial chemotherapy (IACT) via the superficial temporal artery for head and neck cancer. This study aimed to assess the potential of a novel microcatheter with a steerable tip inserted through the ECAS in comparison to an existing hook-type microcatheter. MATERIALS AND METHODS: The same operator used two types of microcatheters alternately for each weekly IACT session with the same patient, and the fluoroscopy time required for catheterization and the arterial selectivity of each microcatheter were compared. RESULTS: Ten patients with advanced head and neck cancer were enrolled. The steerable microcatheter significantly shortened the fluoroscopy time required for catheterization in comparison to the hook-type microcatheter (45.9 ± 4.8 vs 70.2 ± 9.8 s, p < 0.02). The arterial selectivity was equivalent [97.1%, (34/35) vs 88.6%, (31/35), p = 0.36]. No serious adverse events were observed in association with the procedure. CONCLUSION: In combination with an ECAS, the steerable microcatheter might be more useful than the hook-type microcatheter.

A case of congenital granular cell epulis in the maxillary anterior ridge: a study of cell proliferation using immunohistological staining.

Congenital granular cell epulis (CGCE) is a very rare benign tumor that preferentially develops in female infants. The histopathological characteristics of CGCE are very similar to a granular cell tumor, but the histological genesis is unknown. We report a case of a four-day-old female neonate who had a tumor mass in the region of the left maxillary anterior teeth. The rate of cell proliferation was determined by immunostaining with Ki-67 and PCNA, which showed labeling indexes of 16.7 and 15.1%, respectively.

Hyperthermia enhances the antitumor effect of photodynamic therapy with ALA hexyl ester in a squamous cell carcinoma tumor model.

BACKGROUND: Photodynamic therapy (PDT) using 5-aminolevulinic acid is considered to be ineffective in the treatment of tumors with progression to the deep layer. Therefore, for such tumors, a method is required which can enhance the effectiveness of this therapy. We examined the anti tumor effect of the combination of PDT with 5-aminolevulinic acid hexyl ester (hALA) and hyperthermia (HT) in a squamous cell carcinoma (SCC) tumor model. METHODS: A tumor model was prepared by subcutaneously implanting SCC into nude mice, and treated with HT, PDT with hALA (hALA-PDT), or hALA-PDT combined with HT (PDT+HT). The treatment was performed by remodeled near infra-red irradiator which allows the generation of two types of rays for PDT and HT. With HT, the tumor was irradiated for raising the temperature with a light dose of 437.5 J/cm(2). With hALA-PDT, the tumor treated with 250 mg/kg hALA was irradiated with a light dose of 50 J/cm(2). With PDT+HT, the tumor was treated as for hALA-PDT except that the temperature was raised during irradiation with a light dose of 437.5 J/cm(2) (including light dose of 50 J/cm(2) for PDT). RESULTS: The tumor growth rates on Day 12 were 97.10% in HT, 67.55% in hALA-PDT and 33.90% in PDT+HT, and PDT+HT showed significant inhibitory effects on tumor growth, although the anti-tumoral effects of HT and hALA-PDT were not seen. CONCLUSION: hALA-PDT combined with HT demonstrated a significant inhibitory effect on the tumor growth of squamous cell carcinoma showing a progression in the deep layer. This suggests that this therapy is useful for tumors showing progression to the deep layer, which hALA-PDT alone is generally ineffective in treating.

Leiomyomatous hamartoma of the tongue in an infant: a case report.

A case of leiomyomatous hamartoma in the postmedian region of the dorsum of the tongue in a 3-year-old boy is reported. This lesion had been noticed at about 1 year of age but was left untreated. The intensity of the inner region of the mass was homogenous and similar to that of the surrounding tongue muscle on both T1- and T2-weighted images of an MRI. The mass was diagnosed as benign tumor of the tongue and resected. Histopathologically, nodular overgrowth of spindle cells containing eosinophilic cytoplasm was noted in the submucoepithelial connective tissue. In immunohistochemical staining, spindle cells were negative for S-100 protein and positive for vimentin and -SMA, suggesting that these cells were derived from smooth muscle. In the 10 months after surgery, there has been no recurrence of the lesion. To our knowledge, only 26 cases (including the present case) have been diagnosed histopathologically as leiomyomatous hamartoma in the oral cavity between 1945 and 2009. Clinical features, differential diagnosis, and treatment are discussed herein.

A case of desmoplastic ameloblastoma occupying maxillary sinus.

We report a rare case of desmoplastic ameloblastoma lesion that filled the entire maxillary sinus. The patient visited our hospital with a chief complaint of swelling around the upper left premolars. A panoramic X-ray captured an image of a mixture of ill-defined radiolucency and radiopacity from the swollen area to the maxillary sinus. Computed tomography (CT) and Magnetic resononce imaging (MRI) showed that the lesion occupied almost the entire left maxillary sinus and had entered the nasal cavity. A pathologic diagnosis of ameloblastoma was made after biopsy, and the tumor was removed and the marginal bone curetted under general anesthesia. A CT scan at 4 months postoperatively indicated the presence of residual and recurrent tumor in the area of the upper left lateral incisor, and removal and curettage were performed again. Recurrence may be detected relatively easily based on radiographic characteristics, and therefore follow-up with an X-ray examination such as a CT scan is important.

A case of oral multiple primary cancer including Spindle Cell Carcinoma.

Spindle Cell Carcinoma (SPCC) is a relatively rare tumour that is classified as a subtype of squamous cell carcinoma (SCC). Histologically, SPCC is composed of a SCC region and epithelium-derived spindle cells with mesenchymal differentiation. We encountered an interesting case of multiple cancer including SPCC. A histopathologically atypical papillary lesion was found 13 years before our initial examination. Multiple verrucous leukoplakia later developed in the oral mucosa, for which an oral vitamin A derivative (a retinoid) was intermittently administered. Multiple cancer including SPCC subsequently developed in the lower gingiva. We investigated the case histologically and immunohistologically based on the concept of field cancerization.

Synergistic increase in osteosarcoma cell sensitivity to photodynamic therapy with aminolevulinic acid hexyl ester in the presence of hyperthermia.

OBJECTIVE: We observed that two osteosarcoma cell lines from the same tumor displayed marked differences in their sensitivities to photodynamic therapy (PDT) with aminolevulinic acid hexyl ester (hALA-PDT). We investigated why these two closely related lines had different hALA-PDT sensitivities and whether the PDT phototoxicity of the less sensitive cell line could be increased by a simultaneous application of hyperthermia (HT). METHODS: Flow cytometry was used to evaluate the intracellular accumulation of protoporphyrin IX (PpIX), a metabolic product of aminolevulinic acid, in two human mandibular osteosarcoma cell lines (HOSM-1 and HOSM-2) treated with HT, hALA-PDT, or hALA-PDT combined with HT (PDT + HT). With hALA-PDT, cells treated with 0.2 mM hALA were irradiated with a light dose of 10-80 J/cm(2) from a near-infrared irradiator. With PDT + HT, the cells were treated as for hALA-PDT except that the temperature was raised to 43.5 degrees C during irradiation. RESULTS: At 6 h after hALA treatment, HOSM-2 cells carried about 1.53-fold more PpIX than HOSM-1 cells. With hALA-PDT, the survival rate for HOSM-1 cells treated with 80 J/cm(2) irradiation was 35.7%, while that for HOSM-2 cells treated with 40-80 J/cm(2) was below 12%. With PDT + HT, the survival rate for HOSM-1 and HOSM-2 cells treated with 80 J/cm(2) irradiation was 14.1% and 10.7%, respectively. CONCLUSION: A combination therapy comprising hALA-PDT + HT treatment may be very useful for the treatment of tumors containing cells that are insensitive to hALA-PDT, such as the HOSM-1 cell line described in this study.

Radicular cyst in a deciduous tooth: a case report and literature review.

Radicular cyst is comparatively rare in primary teeth. The purposes of this paper were to report the case of a 6-year-old male child with a radicular cyst in a primary mandibular molar tooth, and discuss the causal factors and treatment of this lesion based on a review of the literature.

Relationship between magnetic resonance imaging and histopathologic findings in thrombosis in the oral and maxillofacial region: a case report.

Histopathologic changes are observed during the clinical course of thrombosis, and the evaluation of such changes by magnetic resonance imaging (MRI) might enhance the accuracy of qualitative diagnosis of the disease. The relationship between histopathologic and MRI findings in the chronic phase of deep venous thrombosis (DVT) that developed in the masseter muscle of a 50-year-old Japanese female patient is described. Two regions with different MRI signal intensities were identified, and a 3-layer structure was observed by microscopy. The distinct MRI regions correlated with the microscopic structure, suggesting that MRI can be used for qualitative imaging of a maxillofacial thrombus.

Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model.

In this study, the effectiveness and mechanism of combination therapy of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) with simultaneous hyperthermia (HT) on human-derived osteosarcoma in vivo were examined. A tumor model was prepared by subcutaneously implanting human osteosarcoma into nude mice and local injection of ALA was selected as the administration route. This study demonstrated that both ALA-PDT and the combination of ALA-PDT with HT exhibited significant inhibitory effects on tumor growth. In the group with high total energy, the growth inhibition rates of tumor were 52.3% in ALA-PDT, and 27.3% in ALA-PDT with simultaneous HT (PDT+HT), and the synergetic index was 1.76, demonstrating that the inhibitory effect on tumor growth in ALA-PDT was significantly increased by simultaneous use of HT. In the histological findings, after ALA-PDT, necrosis was observed in the area from the surface to a depth of 2 mm, and only a slight effect was confirmed in deeper layers. On the other hand, after PDT+HT, necrosis was observed in layers even deeper than 2 mm below the surface. Furthermore, based on the immunohistochemical findings of the expression of carbonic anhydrase IX, while weak expression of CAIX was observed after ALA-PDT in an area relatively close to the surface, a positive area extended to the deeper layers after PDT+HT compared with ALA-PDT. In conclusion, PDT+HT demonstrated a significant inhibitory effect on tumor growth of human-derived osteosarcoma, and a synergistic interaction of simultaneous HT. This suggests the possibility that ALA-PDT is useful, not only for the treatment of superficial tumors but also for deep-seated mesenchymal tumors, such as osteosarcoma. Furthermore, the mechanism of the synergistic interaction suggested that ALA-PDT was effective in the deep area of tumors due to the increase of blood flow by mild hyperthermia.

Griseofulvin enhances the effect of aminolevulinic acid-based photodynamic therapy in vitro.

OBJECTIVE: In this study, we investigated whether or not griseofulvin (GF), which is an antimycotic widely used for the oral treatment of skin fungal infections, enhanced the effect of aminolevulinic acid-based photodynamic therapy (ALA-PDT) in vitro, using several tumor cell lines. METHODS: A human squamous cell carcinoma line (KB), two human osteosarcoma cell lines from mandible (HOSM-1, HOSM-2), and the human gingiva-derived fibroblast line (HF), representing normal cells, were used. GF enhancement of ALA-PDT was evaluated by comparing the effect of ALAin combination with GF to the effect of ALAalone (GF enhancement rate of ALA-PDT). Also, the effect of GF on intracellular accumulation of protoporphyrin IX (PpIX) was evaluated by comparing the intracellular accumulation of PpIX in the ALA and GF combined treatment with that of ALA treatment alone (pGF enhancement rate of intracellular PpIX). RESULTS: GFenhancement rate of ALA-PDT was 2.51 in KB cells, and 1.65 and 1.27 in HOSM-1 and HOSM-2 cells, respectively. GF enhancement rates of intracellular PpIX were 1.94 in KB cells, 1.53 in HOSM-1 cells, and 1.19 in HOSM-2 cells. GF enhancement rate of intracellular PpIX followed the same trends as the levels of GF enhancement rate of ALA-PDT in the different cell types. For HF, a large effect was not revealed in this study. CONCLUSION: The present study, although preliminary, strongly suggests that concomitant treatment with ALAand GF may be very useful to enhance the effect of ALA-PDT.

Enhancement of the effect of 5-aminolevulinic acid-based photodynamic therapy by simultaneous hyperthermia.

In the present study, we have investigated a combination of photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and simultaneous hyperthermia (HT) on osteosarcoma (HOSM-1) cells, squamous cell carcinoma (KB) cells and fibroblasts (HF), including an assessment of the differences in the sensitivity of these cells to such treatment in vitro. The intracellular accumulation of protoporphyrin IX (PPIX) formed by metabolism of ALA in mitochondria and the influence of the treatment on the mitochondrial membrane potential were evaluated using flow cytometry. The antitumor effects of HT, PDT using ALA (ALA-PDT) and ALA-PDT combined with HT (PDT+HT) were determined by an MTT assay. Western blot analysis of the expression of heat shock protein 60 (Hsp60) and Hsp70 was performed to evaluate the mitochondrial stress caused by each treatment. The intracellular PPIX accumulation in HOSM-1 cells was about 2-fold higher than that in KB cells. An antitumor effect of ALA-PDT and PDT+HT was obtained in each cell line, and indicated a synergistic interaction of the combination therapy in tumor cells. A marked degree of depolarization of the mitochondrial membrane was observed in both tumor cell lines, and there was no marked difference in the degree of depolarization between the cell lines. Marked expression of Hsp60 was observed in HOSM-1 cells treated with PDT+ HT and ALA-PDT, but not in KB cells. Slightly increased expression of Hsp70 was observed for all treatments in both tumor cell lines. These results suggest that the antitumor effect of ALA-PDT therapy against malignant tumor cells is enhanced by simultaneous HT. Furthermore, the differences in sensitivity to these therapies between the two cell types may have occurred because PPIX was not effectively utilized in HOSM-1 cells, compared to its utilization in KB cells.

Characterization of the human mandibular osteoblastic osteosarcoma cell line HOSM-2 after long-term culture.

We have been subculturing a human mandible-derived osteosarcoma cell line (HOSM-2) for approximately 15 years, and have compared the characters of early generations, which did not exhibit tumorigenicity, to those in the later generations. The shape and doubling time of the cells did not change during long-term culture. The number of chromosomes, however, changed from 59-81 in the 6th generation (modal number: 70) to 54-59 (modal number: 56 and 57), and the chromosomal structure also changed. In addition, the cell line in the later generations showed tumorigenicity in nude mice, and Codon 306 of the p53 gene was mutated to a stop codon due to a point mutation. HOSM-2 cells expressed osteoblast markers, thus confirming them to be osteoblastic osteosarcoma cells. These results showed that changes in certain genes in the HOSM-2 cells led to tumorigenicity in nude mice following long-term culture. In addition, as a mandible-derived cell line with characteristics different from those of limb-derived osteosarcoma cell lines, HOSM-2 cells may be a valuable model for mandibular osteosarcoma and osteoblasts.

Efficacy of combined photodynamic and hyperthermic therapy with a new light source in an in vivo osteosarcoma tumor model.

OBJECTIVE: In this study, we investigated the efficacy of Super Lizer (SL) as a new light source in photodynamic therapy (PDT) with hyperthermia in an in vivo osteosarcoma tumor model. MATERIALS AND METHODS: Nude mice in three study groups (PDT only, PDT with hyperthermia in low energy, and PDT with hyperthermia in high energy) and three control groups (no treatment, photosensitizer only, and hyperthermia only) were implanted subcutaneously with human osteosarcoma cells and injected with a photosensitizing hematoporphyrin derivative (HPD) at a total dose of 10 mg/kg, in all study groups and in control group 2. At 72 h after light treatment, mice were sacrificed. RESULTS: The tumor volume growth rates in the heat-only (1.50) and PDT-only (1.40) groups were significantly lower than the growth rate in the no-treatment group (1.82). Further, the tumor volume growth rate in the PDT with hyperthermia in high-energy group (1.19) was significantly lower than in the heat- or PDT-only groups. CONCLUSION: Although non-laser PDT, including SL-PDT, may be beneficial only in the treatment of superficial tumors because of limited light penetration, PDT combined with hyperthermia may extend the utility of PDT in antitumor treatment. The use of SL as a new light source in PDT may significantly advance antitumor therapy due to its simplicity, ease, and cost benefit.