Prevention of tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaws with basic fibroblast growth factor: An experimental study in rats.

Osteonecrosis of the jaw induced by administration of bisphosphonates (BPs), BP-related osteonecrosis (BRONJ), typically develops after tooth extraction and is medically challenging. As BPs inhibit oral mucosal cell growth, we hypothesized that suppression of the wound healing-inhibiting effects could prevent BRONJ onset after tooth extraction. Since basic fibroblast growth factor (bFGF) promotes wound healing, but has a short half-life, we examined whether the initiation of BRONJ could be prevented by applying a bFGF-containing gelatin hydrogel over the extraction sockets of BRONJ model rats. Forty-three rats, received two intravenous injections of zoledronic acid 60 µg/kg, once per week for a period of 2 weeks, underwent extraction of a unilateral lower first molar. The rats here were randomly assigned to the bFGF group (n = 15 rats, gelatin hydrogel sheets with incorporated bFGF applied over the sockets); the phosphate-buffered saline (PBS) group (n = 14 rats, gelatin hydrogel sheets without bFGF applied over the sockets); or the control group (n = 14 rats, nothing applied over the sockets). One rat in the bFGF group was sacrificed immediately after tooth extraction. Twenty-one rats were sacrificed at 3 weeks, and the remaining 21 rats were sacrificed at 8 weeks after tooth extractions. The harvested mandibles were analyzed using micro-computed tomography and sections were evaluated qualitatively for mucosal disruption and osteonecrosis. The incidence of osteonecrosis at 8 weeks after tooth extraction was 0% in the bFGF group, 100% in the PBS group, and 85.7% in the control group. The frequency of complete coverage of the extraction socket by mucosal tissue was significantly greater in the bFGF group than in the other groups. These results suggest that application of bFGF in the extraction socket promoted socket healing, which prevented BRONJ development. The growth-stimulating effects of bFGF may have offset the inhibition of wound healing by BP.

Maxillofacial bone regeneration with osteogenic matrix cell sheets: An experimental study in rats.

OBJECTIVE: Regeneration of maxillofacial bone defects, characterized by relatively small but complicated shapes, poses a significant clinical challenge. Osteogenic matrix cell sheets (OMCSs) have osteogenic ability and good shaping properties and may be ideal graft materials. Here, we assessed whether implantation of OMCSs could be used to repair maxillofacial bone defects. DESIGN: We adopted a rat mandibular symphysis model. The rat mandible is formed by a paired bone and the central portion consisting of fibrous tissue. There is no bone tissue at the site; accordingly, this site was interpreted as a physiological bone gap and was used for evaluation. Rat bone marrow cells were cultured in medium containing dexamethasone and ascorbic acid phosphate to create OMCSs. The OMCSs were implanted into the rat mandibular symphysis without a scaffold. Microcomputed tomography and histological analyses were conducted after 2, 4, and 8 weeks. RESULTS: Two weeks after implantation, microcomputed tomography images and histological sections showed some sparse granular calcification tissue within the bone gap at the mandibular symphysis. At 4 weeks, the calcification tissue spread, and the gap of the mandibles were continued. At 8 weeks, this continuous new bone tissue was matured. The experimental group showed abundant new bone tissue in the group with OMCS implantation, but not in the group with sham implantation. CONCLUSIONS: Our present results indicated that use of OMCSs may be an optimal approach towards achieving maxillofacial regeneration.

[Effect of transarterial chemoembolization for recurrent desmoid tumor - a case report].

Desmoid fibromatosis is classified as a benign soft tissue tumor regardless of its local invasive behavior and its, local recurrence rate is 57-85% after local resection. A 19 y/o male patient with post-operative recurrence of a desmoid tumor in the shoulder was initially treated by arterial embolization; however, no improvement of symptoms was obtained. As second-line treatment, 20 mg of epirubicin, 50 mg of cisplatin and 250 mg of 5-FU were infused to tumor-related arteries and embolization was performed with a super absorbent polymer microsphere. After a single session of treatment, reduction of tumor size and improvement of symptoms were achieved. The same treatment was repeated three times without major complications. Considerable reduction of tumor was obtained after treatment. Chemo-embolization should be considered for the postoperative recurrence of desmoid fibromatosis, in order to prevent loss of function and maintain a high QOL for the patient.

Transcatheter arterial embolization with spherical embolic agent for pulmonary metastases from renal cell carcinoma.

PURPOSE: This retrospective study aimed to evaluate the safety and local efficacy of transcatheter arterial embolization (TAE) with superabsorbent polymer microspheres (SAP-MS) in patients with pulmonary metastases from renal cell carcinoma (RCC). METHODS: Sixteen patients with unresectable pulmonary metastases from RCC refractory to standard therapy were enrolled to undergo TAE with the purpose of mass reduction and/or palliation. The prepared SAP-MS swell to approximately two times larger than their dry-state size (100-150 µm [n = 14], 50-100 µm [n = 2]). Forty-nine pulmonary nodules (lung n = 22, mediastinal lymph node n = 17, and hilar lymph node n = 10) were selected as target lesions for evaluation. Local tumor response was evaluated 3 months after TAE according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The relationship between tumor enhancement ratio by CT during selective angiography and local tumor response was evaluated. RESULTS: The number of TAE sessions per patient ranged from 1 to 5 (median 2.9). Embolized arteries at initial TAE were bronchial arteries in 14 patients (87.5 %) and nonbronchial systemic arteries in 11 patients (68.8 %). Nodule-based evaluation showed that 5 (10.2 %) nodules had complete response, 17 (34.7 %) had partial response, 15 (30.6 %) had stable disease, and 12 (24.5 %) had progressive disease. The response rate was significantly greater in 22 lesions that had a high tumor enhancement ratio than in 27 lesions that had a slight or moderate ratio (90.9 vs. 7.4 %, p = 0.01). Severe TAE-related adverse events did not occur. CONCLUSION: TAE with SAP-MS might be a well-tolerated and locally efficacious palliative option for patients with pulmonary metastases from RCC.

Hard tissue-forming potential of stem/progenitor cells in human dental follicle and dental papilla.

OBJECTIVE: The existence of stem/progenitor cells in dental tissue has been suggested but their characterization in the human tooth germ remains elusive. The purpose of this study was to investigate these cells in human dental follicles and dental papillae at the crown-forming stage and compare their potential for hard tissue formation. DESIGN: We used dental follicle cells (DFCs) and dental papilla cells (DPCs) derived from dental follicles and dental papillae at the crown-forming stage and compared their proliferative capacity, cell surface antigens and ability to form hard tissue in vitro and in vivo. RESULTS: Both DFCs and DPCs had extensive proliferation ability, expressed similar cell surface antigens and were capable of forming hard tissue in vivo as well as in vitro. However, there were two differences between DFCs and DPCs. First, DPCs had a significantly higher calcium accumulation than that in DFCs. Second, DFCs expressed a cementoblast marker, whereas DPCs expressed an odontoblast marker. CONCLUSIONS: We propose that dental follicles and dental papillae at the crown-forming stage contain different types of stem/progenitor cells and may have hard tissue-forming ability in a possibly origin-specific lineage direction.

In search of necessary mouthguard thickness. Part 1: From the viewpoint of shock absorption ability.

PURPOSE: To date, the minimum thickness required for a mouthguard has been assumed to be around 2 mm to 4 mm. However, this figure is based mostly on experience and is yet to be standardized. The purpose of this study is to determine the minimum thickness required to obtain sufficient energy absorption. METHODS: The thicknesses of the tested ethylene vinyl acetate) samples were 1, 2, 3, 4, 5, and 6 mm. The pendulum- type testing equipment used in the present study was also used in a series of earlier studies. Three types of sensors (strain gauge, accelerator, and load cell) and two different impact objects (a steel ball and baseball) were used. RESULTS: The results showed that all the above-mentioned mouthguard thicknesses reduced shocks for all the three types of sensors and both types of impact objects; little difference was observed between sensors and clear results were obtained for the steel ball. An improvement in the energy absorption was observed with an initial increase in the thickness. However, a further increase in the thickness from 4 mm to 5 mm and 6 mm tended to yield a smaller improvement in energy absorption. CONCLUSION: Within the limitations of this study, from the viewpoint of energy absorption ability, the minimum thickness required for a mouthguard is 4 mm, which is generally too large from the viewpoint of player comfort. This finding indicates the necessity of improving the impact absorption ability of mouthguards by considering new designs and developing new materials.

In vitro mineralization by mesenchymal stem cells cultured on titanium scaffolds.

Titanium has been utilized in the field of orthopaedic and dental reconstructive surgery, but mineralization through osteogenic differentiation of osteogenic cells on titanium surfaces has not been fully investigated. Here we cultured rat mesenchymal stem cells (MSCs) on the surfaces of titanium dishes in osteogenic media containing calcein which is a calcium-binding fluorescence dye. On titanium dishes, MSCs showed high viability to adhere to the surfaces and excellent proliferation. At day 14 of culture, MSCs differentiated into osteoblasts to form mineralized matrices on titanium dishes as well as tissue culture polystyrene (TCPS) dishes which are widely recognized as optimal culture substrates. Calcein was incorporated into the bone minerals fabricated by MSCs cultured on both substrates to show green emission under fluorescence microscopy. The fluorescence intensity was quantified with an image analyser during culture periods. These results indicate that the surfaces of titanium showed a high adhesion/proliferation potential to MSCs and that the titanium effectively supported the osteogenic differentiation of MSCs comparable to TCPS dishes. Therefore, the titanium is an effective scaffold that is applicable in bone reconstruction surgery.

Adult T-cell leukemia in a liver transplant recipient that did not progress after onset of graft rejection.

A liver allograft recipient developed acute-type adult T-cell leukemia (ATL) during tacrolimus treatment, 2 years after undergoing transplantation for subacute fulminant hepatitis. Both donor and recipient were asymptomatic carriers of human T-cell lymphotropic virus type I (HTLV-I), but the ATL cells originated from the recipient. Tacrolimus treatment was discontinued, and combination chemotherapy was administered. The patient achieved complete remission, but the transplanted liver was acutely and chronically rejected. The patient did not respond to rescue therapy with tacrolimus, prednisolone, and mycophenolate mofetil and died of hepatic failure. Liver biopsies showed CD4+ ATL cell infiltration at the onset of ATL but not at the terminal stage. Moreover, Southern blotting revealed clonal integration of HTLV-I into the host genome of lymphoma cells at onset but not at the terminal stage. ATL after liver transplantation has not been previously described. The clinical course of the posttransplantational ATL was atypical, because it did not progress after the onset of rejection.

Osteogenic differentiation of human dental papilla mesenchymal cells.

We isolated dental papilla from impacted human molar and proliferated adherent fibroblastic cells after collagenase treatment of the papilla. The cells were negative for hematopoietic markers but positive for CD29, CD44, CD90, CD105, and CD166. When the cells were further cultured in the presence of beta-glycerophosphate, ascorbic acid, and dexamethasone for 14 days, mineralized areas together with osteogenic differentiation evidenced by high alkaline phosphatase activity and osteocalcin contents were observed. The differentiation was confirmed at both protein and gene expression levels. The cells can also be cryopreserved and, after thawing, could show in vivo bone-forming capability. These results indicate that mesenchymal type cells localize in dental papilla and that the cells can be culture expanded/utilized for bone tissue engineering.

[Questionnaire survey of dentists who made their own mouthguards].

PURPOSE: Most of the mouthguards on the market are inferior in fit and occlusion related to feeling and injury prevention capacity. Therefore, it is necessary to use appropriate custom-made mouth-guards. This research aimed to obtain data for the selection, improvement, and spread of mouthguards in the future. A questionnaire survey of dentists who had made four kinds of mouthguard was conducted in a mouthguard seminar. METHODS: The questionnaire survey concerning "feeling", "difficulty of production", and "selection when considering use and spread" was done for four kinds of mouthguard. The evaluations were made using a ten-point method with the Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: Concerning the feeling: The laminated mouthguard was evaluated the highest, followed in order by improvement type, vacuum, and boil & bite. Concerning the production: The evaluation differed from other questionnaire items. No significant difference was found among all four kinds of mouthguard, so there was no difference in the fabrication difficulty. Concerning the selection and spread: The evaluation was almost the same as for the feeling. The laminated mouthguard was assessed to be the best mouthguard. CONCLUSIONS: The boil & bite mouthguard which is widespread was evaluated the lowest in all items except production. Therefore, it is necessary to encourage players to use an appropriate custom-made type in view of safety, wearing feeling, and dental occlusion.

Outcome of patients with hepatitis C virus-related single, small hepatocellular carcinoma.

To clarify the cumulative recurrence-free interval and survival rate with hepatitis C virus (HCV)-related single, small hepatocellular carcinoma (HCC), we studied 32 patients with surgical resection, 61 with ablation therapy and 28 with transcatheter chemoembolization (TACE). A log-rank test revealed that there were no significant differences in the recurrence-free interval (p = 0.08) and survival (p = 0.279) between the resection and the ablation groups. Univariate analysis using the Cox proportional hazards regression model showed initial treatment (p = 0.0051) was associated with recurrence-free interval. Platelet count (p = 0.009), indocianine green retention rate at 15 minutes (p = 0.003), Child-Pugh classification (p = 0.001), serum albumin level (p = 0.0012) and serum total bililubin (p = 0.015) were associated with survival. Hence patients with HCV-related single, small HCC should be treated according to their hepatic reserve.

Systemic combined chemotherapy with low dose of 5-fluorouracil, cisplatin, and interferon-alpha for advanced hepatocellular carcinoma: a pilot study.

The purpose of this pilot study was to evaluate the efficacy and adverse events of systemic combined chemotherapy with low dose of 5-fluorouracil (250 mg/m2, 5 days), cisplatin (10 mg/m2, 5 days), and interferon-alpha (2.5 million units, three times weekly) for advanced hepatocellular carcinoma (HCC) underlying liver cirrhosis. Six patients who had advanced HCC with tumor thrombi in the main portal trunk were enrolled in this study. Partial response was achieved in 2, stable disease in 1, and disease progressed in 3. Objective responses were achieved in 2 (33%), however, marked decreases of alpha-fetoprotein protein and protein-induced vitamin K antagonist or absence (PIVKAII) levels were also seen in one patient (stable disease). Four patients showed hematologic or renal toxicity, which were well tolerated and managed. Our systemic combined chemotherapy resulted in favorable response and was well tolerated in those with advanced HCC underlying liver cirrhosis, complicated by leukocytopenia and thromobocytopenia.

Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation.

BACKGROUND: The objectives of this study were to clarify risk factors for local tumor recurrence and to determine which patients with hepatocellular carcinoma (HCC) are most suitable for a single session, single application of percutaneous radiofrequency (RF) ablation. METHODS: Fifty-six consecutive patients with 65 HCC tumors measuring 2 cm (risk ratio [RR], 4.9; 95%CI, 1.3-16.4; P = 0.019) and subcapsular location (RR, 5.2; 95%CI, 1.7-16.6; P = 0.005) were associated independently with local recurrence. The other four factors were not associated with local recurrence in this study. CONCLUSIONS: A single session, single application of RF ablation produced favorable local control. Patients who have nonsubcapsular HCC tumors measuring

Outcome of patients with hepatitis C virus-related hepatocellular carcinoma occurring after interferon therapy.

To determine whether previous IFN therapy for chronic hepatitis C (HCV) infection influences the outcome of patients with hepatocellular carcinoma (HCC), 143 patients were enrolled in this study. Of 143 patients, 48 had received previous IFN therapy (IFN group) and the remaining 95 had not (untreated group). We estimated distant intrahepatic recurrence-free intervals and disease-specific survivals of the two groups by the Kaplan-Meier method and analyzed the difference by the log-rank test. Factors determining distant intrahepatic recurrence-free interval and disease-specific survival were studied by univariate and multivariate analysis using Cox proportional hazards regression model. The proportion of patients with single tumors was significantly higher in the IFN group (p = 0.026). The IFN group showed a significantly higher distant intrahepatic recurrence-free interval (p = 0.001) and disease-specific survival (p = 0.003). Moreover, multivariate analysis indicated that previous IFN therapy for chronic HCV infection was a significant independent factor for distant intrahepatic recurrence-free interval and disease-specific survival. These results indicate that previous IFN therapy reduces multicentric hepatocarcinogenesis of HCV-related HCC and improves the patients' survival.