Tatsuo Shirota

Postoperative function after implant insertion in vascularized bone grafts in maxilla and mandible

&NA; Between 1988 and 1992, 80 Branemark‐type implants were inserted in 18 patients during reconstruction of the mandible or maxilla with vascularized iliac crest or scapula grafts with or without additional soft tissue pedicles. In these procedures, nine vascularized bone grafts were combined with a primary insertion of 32 implants and a secondary insertion of 48 implants. Twelve patients are currently wearing the implant‐borne dentures. From 32 implants inserted primarily, eight could not be used for prosthodontic rehabilitation because three were lost with a graft, three were left as sleepers, and two demonstrated a lack of osseointegration. None of the implants inserted secondarily in grafts were lost. Primary implant insertion should be performed only in close cooperation with the prosthodontist and in selected cases, for example, in freeend reconstruction of the mandible with a straight graft and where a limited number of implants is needed. Although restoration of masticatory function in patients with head and neck cancer can be achieved, compared with a healthy control group, functional impairments remain. Patients subjectively favor the nonreconstructed side of the mandible or maxilla for chewing. These findings can be correlated with a postoperative follow‐up investigation using a miniature force transducer and the T‐scan system. (Plast, Reconstr, Surg. 97: 719, 1996.)

Bone reactions to titanium screw implants in ovariectomized animals

OBJECTIVE The purpose of this study was to investigate the reactions of bone tissue after the placement of implants into the tibiae of osteopenic model rats. STUDY DESIGN Commercially pure titanium screw implants were placed in the bilateral proximal tibial metaphyses 168 days after ovariectomy had been performed on 12-week-old female Wistar rats. For control purposes, implants were similarly placed in sham-ovariectomy rats. The healing process was examined histologically by means of undecalcified sections at various intervals from 7 to 168 days after implantation. Through use of an automated imaging analytic system, changes in relative bone mass and implant-bone contact were histomorphometrically evaluated. RESULTS In the cortical bone area, only a slight difference in bone contact was noted with the implant until 28 days after implantation. However, ovariectomy significantly affected bone contact at 56 days after implantation. The rate of bone contact in the cancellous bone area and the relative bone mass around the implant were significantly lower in the test group than in the control group. CONCLUSIONS It is considered that a decrease in bone mass causes a reduction in the contact area between implant and bone and may also cause a reduction in the supporting ability of the implant because of thinning of the surrounding bone tissue.

Bone reactions around hydroxyapatite-coated implants in ovariectomized rats☆☆☆

OBJECTIVE The purpose of this study was to investigate bone reaction after implantation in an estrogen-deficient state by examining the changes in bone reactions within tissue surrounding implants in ovariectomized rats. STUDY DESIGN Ninety-six 12-week-old female Wistar rats were used in the study; they were divided into 2 groups, an ovariectomized group and a sham-operated group. Hydroxyapatite-coated implants were placed in the proximal metaphyses of the tibiae 21 days after surgery. The tibiae were examined histologically by undecalcified sections at various intervals from 7 to 168 days after surgery. RESULTS In the cortical bone area of the ovariectomized rats, the procedure did not induce any apparent changes in bone volume around the implant or in bone contact with the implant in comparison with the sham-operated rats. In contrast, both bone volume around the implant and contact of the implant with new bone were significantly decreased in the cancellous bone area in the ovariectomized rats in comparison with the sham-operated rats. CONCLUSIONS Ovariectomy did not seriously affect bone healing after the placement of implants in cortical bone areas, but it reduced the bone contact ratio and the bone in the cancellous bone area.

Hypoxia Induces Resistance to 5-Fluorouracil in Oral Cancer Cells Via G1 Phase Cell Cycle Arrest

Malignant tumors are exposed to various levels of hypoxic condition in vivo. It has been known that tumor cells under hypoxia are resistant to chemotherapies. To clarify the mechanism of the hypoxia-induced chemoresistance, we evaluated the effects of hypoxia on the resistance of oral squamous cell carcinoma (OSCC) cell lines to 5-fluorouracil (5-FU). OSCC cells were divided to two groups by the proliferation activity under hypoxic condition; hypoxia-resistant (HR) and hypoxia-sensitive (HS) cells. Growth of HS cells were inhibited by hypoxia and introduced to G(1) arrest in cell cycle. 5-FU effect on HS cell viability was markedly reduced in hypoxic condition without an induction of chemoresistant related protein, P-glycoprotein. However, proliferation, cell cycle, and 5-FU sensitivity of HR cells were not affected by hypoxia. Hypoxia-inducible factor (HIF)-1alpha was induced by hypoxia in all OSCC cell lines, but diminished in HS cells within 48h. Expression of p21 and p27 was strongly augmented and CyclinD expression was reduced by hypoxia in HS cells. However, the expression of these proteins was constitutive in HR cells during 48h hypoxic culture. Phosphorylation of mammalian target of rapamycin (mTOR) was reduced by hypoxia in HS cells. From these findings, we concluded that HS OSCC cells acquire 5-FU resistance under hypoxia by G(1)/S transition through an upregulation of cell cycle inhibitors.

Histologic and microradiologic comparison of block and particulate cancellous bone and marrow grafts in reconstructed mandibles being considered for dental implant placement

PURPOSE Patterns of healing were investigated in mandibles reconstructed with three different techniques to assess their readiness for implant placement. PATIENTS AND METHODS The subjects were 10 patients who had undergone mandibular reconstruction with either nonvascularized iliac block bone grafts (group 1; 3 patients), particulate cancellous bone and marrow (PCBM) grafts (group 2; 3 patients) for mandibular discontinuity, or PCBM grafts for mandibular marginal defects (group 3; 4 patients). Six (groups 2 and 3) or 12 months (group 1) after mandibular reconstruction, bone biopsy specimens were obtained for histologic examination with a trephine bur. As controls, bone specimens were obtained from ungrafted mandibles of patients undergoing dental implant placement. Undecalcified specimens were embedded in polyester resin and examined by routine light microscopy and microradiography. RESULTS The morphology of the specimens from group 1 was similar to that of group 2, but not to that of the control subjects. However, the morphology of specimens from group 3 was generally similar to that of control subjects. CONCLUSION These results suggest that mandibular reconstruction with PCBM grafts allows the placement of dental implants sooner than reconstruction with block bone grafts.

Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese

Massively parallel sequencing of target regions, exomes, and complete genomes has begun to increase the opportunities for identifying genetic variants underlying rare and common diseases dramatically. Here we applied exome resequencing to primary failure of tooth eruption (PFE) to identify the genetic causality of the disease. Two Japanese families having PFE were recruited and examined by genome‐wide linkage study and subsequently exome analyses. Linkage analyses of these two families comprising eight affected individuals and two unaffected individuals revealed linkage signals at 10 loci with a maximum LOD score of 1.5. Four affected individuals in one family were pooled and further processed for exome analysis, followed by massive parallel sequencing. After three‐step filtering including annotation and functional expectation, three variants were found to be candidates for PFE. Among the three variants, only a novel variant of parathyroid hormone 1 receptor gene (PTH1R), R383Q, was cosegregated in the first PFE family. Accordingly, we screened the gene for variants at all coding exons and the respective intron‐exon boundaries in the second family and two sporadic individuals with PFE. We also identified a novel missense variant, P119L, cosegregating in the second family and missense variants P132L and R147C in the sporadic cases. These variants all were in the highly conserved region across zebrafish to chimpanzee and not observed in 192 unrelated controls, supporting the pathogenicity of the variants. The combination of linkage and exome analyses employed in this study provides a powerful strategy for identifying genes responsible for Mendelian disorders.

Analysis of bone volume using computer simulation system for secondary bone graft in alveolar cleft.

The purpose of this study was to measure the bone volume necessary for secondary bone grafting in the alveolar cleft using surgical simulation software based on three-dimensional computed tomography (CT) scan data, to compare this measurement with the actual volume of the bone graft, and to evaluate consistency. The subjects were 13 patients with cleft lip and palate who underwent CT using a cone-beam CT unit (CB-CT) 1 month before surgery, followed by bone grafting with particulate cancellous bone and marrow (PCBM) to close the cleft. The bone volume necessary for grafting was measured based on the CB-CT scan data. Correlation analysis, a test of the population mean between two samples, and Wilcoxons signed rank test were conducted between these measurements and the actual bone volume (PCBM volume) used for grafting. SPSS was used for statistical analysis, and the level of significance was set below the 5% level. The results showed a significant correlation, with no significant differences between the two in all tests. These results suggest that measuring and preoperatively calculating the bone volume necessary for bone grafting with surgical simulation software using CB-CT scan data is beneficial.

Long-Term Study of Dental Implants Placed into Alveolar Cleft Sites:

Objective: To evaluate the long-term prognosis of dental implants placed into cleft sites after bone grafting in a relatively large number of cases in order to clarify the usefulness of the modality. Patients: Forty-seven patients with unilateral (dental, n = 32) or bilateral (n = 15) clefts of the alveolar process were included in this study. Interventions: A total of 71 implants, including smooth- or rough-surface titanium, and hydroxyapatite (HA)-coated implants, were placed after bone grafting from the anterior iliac crest and/or mandible. The placed implants were 13 to 15 mm in length. Main outcome: The follow-up period was from 21 to 120 months (average = 60 months). Implant survival rates were calculated as cumulative survival. Marginal bone loss (MBL) from the implant shoulder was examined, with statistical analyses performed on the influence of simultaneous bone graft and surface characteristics. Results: At the end of the clinical follow-up period, all implants except one were in situ and stable. Thus, the overall survival rate was 98.6% at the end of the first year and remained the same until the end of observation. Titanium implants with smooth surfaces had the lowest MBL with almost negligible regression slope, although some implants had relatively high MBL by the end of the first year. Conclusions: Implant therapy in the cleft site offers a reliable option for patients. Particular attention should be focused preoperatively on whether bone volume can provide primary implant stability.

An experimental study of healing around hydroxylapatite implants installed with autogenous iliac bone grafts for jaw reconstruction

The purpose of this study was to evaluate the use of hydroxylapatite implants (HA) with autogenous bone grafts for jaw reconstruction. After autogenous iliac bone grafts were transplanted to 36 rabbit mandibles, an HA implant was installed into the graft immediately (IM group), or 90 days (90D group), or 180 days (180D group) later. The animals were killed 7, 14, 30, 60, 90, and 180 days after the HA implant placement. The healing process was examined histologically, and histomorphometric measurements were made with a computer-based image analyzer to quantify the percentage of HA-bone bonding and trabecular bone in the medullary cavity. In the IM group, the HA-bone bonding tended to be deterred by fibrous tissue, and the rate of HA-bone bonding (BBSR) was less than that of the other groups. The trabecular bone around the implants tended to decrease after 30 days in all groups. However, the average of the trabecular bone specific volume (tVsp) in the 90D group was about 10% higher than that in the other groups. From these results, it is concluded that in clinical use of HA-coated dental implants with autogenous bone grafts, the time of installation should not be immediately after the bone graft, but when there is sufficient newly formed trabecular bone to enhance HA-bone bonding.

Immediate insertion of two types of implants into vascularized bone grafts used for mandibular reconstruction in miniature pigs

Reaction of bone tissue was investigated after placement of two different types of implants in vascularized iliac bone grafting. After the mandibles of six Göttingen minipigs were reconstructed with vascularized bone of the iliac crest, hydroxyapatite-coated implants and titanium screw implants were placed in the graft. The animals were killed at 14, 28, and 56 days after the implantation, and the healing processes were examined histologically. In the vascularized bone graft, new bone formed well around the implants, but some of the implant surfaces were covered with soft tissue by advancing bone resorption. The results suggest that a hydroxyapatite-coated implant as well as a titanium screw-type implant might be applied with a vascularized bone graft for jaw reconstruction. However, implants placed simultaneously with the vascularized bone graft had less osteointegration than implants placed in nongrafted control sites.