Comparing nerve-mediated FGF signalling in the early initiation phase of organ regeneration across mutliple amphibian species.

Amphibians have a very high capacity for regeneration among tetrapods. This superior regeneration capability in amphibians can be observed in limbs, the tail, teeth, external gills, the heart, and some internal organs. The mechanisms underlying the superior organ regeneration capability have been studied for a long time. Limb regeneration has been investigated as the representative phenomenon for organ-level regeneration. In limb regeneration, a prominent difference between regenerative and nonregenerative animals after limb amputation is blastema formation. A regeneration blastema requires the presence of nerves in the stump region. Thus, nerve regulation is responsible for blastema induction, and it has received much attention. Nerve regulation in regeneration has been investigated using the limb regeneration model and newly established alternative experimental model called the accessory limb model. Previous studies have identified some candidate genes that act as neural factors in limb regeneration, and these studies also clarified related events in early limb regeneration. Consistent with the nervous regulation and related events in limb regeneration, similar regeneration mechanisms in other organs have been discovered. This review especially focuses on the role of nerve-mediated fibroblast growth factor in the initiation phase of organ regeneration. Comparison of the initiation mechanisms for regeneration in various amphibian organs allows speculation about a fundamental regenerative process.

Long-Term Changes in Bone Height After Mandibular Reconstruction Using a Free Fibula Graft in an Elderly Population.

PURPOSE: This study evaluated short-term and long-term changes in bone height after mandibular reconstruction using an osteotomized fibula graft, with the aim of identifying factors associated with atrophy of the graft in an elderly population. PATIENTS AND METHODS: This retrospective study involved patients who underwent mandibular reconstruction using a free vascularized fibula graft from 2005 through 2015 and had at least 12 months of follow-up. Postoperative panoramic radiographs were used to measure bone height at standardized locations on each segment of the graft at 1 year postoperatively and at later follow-up. RESULTS: The sample was composed of 30 patients (15 men, 15 women; mean age, 62.6 years; age range, 50 to 80 years). According to the HCL classification (H, hemimandibular segment including the condyle; C, central segment including both mandibular canine teeth; L, lateral segment without the condyle), mandibular defect types were L (n = 19), LC (n = 7), LCL (n = 3), and H (n = 1). There were 0 to 3 segmental osteotomies with the fibula graft. None of the patients received an osseointegrated dental implant during a mean follow-up of 4.0 years (range, 1.5 to 9.7 yr). All patients underwent reconstruction of the mandibular body, 10 of whom also underwent reconstruction of the mandibular ramus. Atrophy of the fibula graft was observed in 9.9 and 15.0% of the body segment and 5.9 and 6.6% of the ramal segment at 1 year postoperatively and at later follow-up, respectively. Graft hypertrophy occurred in the ramal segment in 2 patients. Multivariate analysis showed a significantly higher rate of graft atrophy in women than in men at later follow-up (P = .033). CONCLUSIONS: Fibula grafts showed long-term stability, and in 2 cases even a gain in bone height, in this elderly population. Female gender was identified as a risk factor for atrophy of the fibula bone graft in the body segment of the reconstructed mandible.

Use of FDG-PET to detect a chronic odontogenic infection as a possible source of the brain abscess.

This study describes the use of (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to detect a chronic odontogenic infection as the possible origin of a brain abscess (BA). A 74-year-old man with esophageal carcinoma was referred to our department to determine the origin of a BA in his oral cavity. He had no acute odontogenic infections. The BA was drained, and bacteria of the Staphylococcus milleri group were detected. Whole body FDG-PET revealed that the only sites of definite uptake of FDG were the esophageal carcinoma and the left upper maxillary region (SUVmax: 4.5). These findings suggested that the BA may have originated from a chronic periodontal infection. Six teeth with progressive chronic periodontal disease were extracted to remove the possible source of BA. These findings excluded the possibility of direct spread of bacteria from the odontogenic infectious lesion to the intracranial cavity. After extraction, there was no relapse of BA.

Refinements in the reconstruction of bisphosphonate-related osteonecrosis of the jaw.

The recommended treatment strategy for stage 3 bisphosphonate-related osteonecrosis of the jaw (BRONJ) is currently rigid plate fixation without bone reconstruction. However, a recent systematic review indicated the utility of microsurgical reconstruction after resection of BRONJ. Several types of flaps have been described but their applications are controversial. Here we present a detailed reconstruction plan for obtaining better outcomes in patients with maxillary and mandibular BRONJ. Given that progressive maxillary BRONJ is often invasive to the skin, including the eyelid, leading to functional loss such as leakage of discharge and ectropion, several revision surgeries are needed to increase the volume in the defect after the free flap transfer. For progressive mandibular BRONJ, hemi-mandibulectomy to subtotal mandibulectomy with an adequate margin from the necrotic bone is necessary, followed by a well-designed fibular free flap.

Oral health care reduces the risk of postoperative surgical site infection in inpatients with oral squamous cell carcinoma.

PURPOSE: Postoperative wound infection (WI) is a main complication after head and neck surgery. Poor oral health may be a risk factor for WI. We therefore assessed the contribution of oral health care in preventing postoperative WI in patients with oral squamous cell carcinoma (OSCC). METHODS: A total of 66 consecutive inpatients with OSCC (mean age, 68 years) was divided into two groups that did or did not receive oral health care. There were no significant between group differences in gender, age, or T-, N-, or clinical stage. Patients in the care group were given oral health care plans by doctors of oral medicine, whereas patients in the control group were not. Twenty-three variables were recorded for each patient. RESULTS: WI was observed in 14/66 patients (21%), three (3/33 = 9%) in the care group and 11 (11/33 = 33%) in the control group (p < 0.025). Univariate statistical analysis showed that 11 factors correlated with WI significantly: T-stage, clinical stage, wearing of dentures, tracheostomy, neck dissection, tissue transplantation, oral health care, preoperative radiation, blood transfusion, operation time, and blood loss. In multiple logistic regression analysis, only two factors were significant independent risk factors for WI: tissue transplantation (p = 0.01; odds ratio, 24.5) and lack of oral health care (p = 0.04; odds ratio, 6.0). CONCLUSION: Oral health care may reduce the risk of postoperative WI in patients with OSCC.

Clinical study of treatment methods and associated factors in mandibular osteoradionecrosis.

This study aimed to determine the appropriate treatment methods and evaluate associated factors by comparing nonoperative treatment alone with a combination of both nonoperative and surgical treatment in 34 patients with mandibular osteoradionecrosis (mORN). The associated cure factors were analyzed by Cox regression. Propensity scores were calculated from factors that were not significant in the univariate analysis and used as covariates in the multivariate analysis. The cure rate among patients who received nonoperative and surgical treatment was higher than that observed with nonoperative treatment alone. Only the treatment method was associated with cure in both univariate and multivariate analyses.

Neural regulation in tooth regeneration of Ambystoma mexicanum.

The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration.

Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: Part III of a cohort study.

OBJECTIVE: Sequential postoperative salivary interleukin-6 (IL-6) concentrations were examined in patients with oral squamous cell carcinoma (OSCC) who had early or late locoregional recurrences or those who did not. STUDY DESIGN: Twenty-seven consecutive patients with OSCC were originally included in the study. All patients underwent radical surgery. Four saliva samples were collected before (periods I and II) and after (periods III and IV) surgery, and IL-6 concentrations were measured. RESULTS: Although postoperative (period III: at the time of discharge) salivary IL-6 level was significantly higher in patients with early locoregional recurrence (P = .02) than in those without, no such relationships were observed for preoperative IL-6 concentrations (periods I and II). Postoperative (period IV: 24 months after surgery) IL-6 level was significantly higher in patients with late locoregional recurrence (P = .03) than in those without, but no such relationships were observed for IL-6 concentrations in periods I, II, and III. CONCLUSIONS: Sequential postoperative salivary IL-6 concentration may be a useful marker for diagnosis of early and late locoregional recurrence in OSCC.

Correlation between salivary interleukin-6 levels and early locoregional recurrence in patients with oral squamous cell carcinoma: preliminary study.

BACKGROUND: We have demonstrated that salivary interleukin-6 (IL-6) concentrations change during the treatment in patients with oral squamous cell carcinoma (OSCC). We sought to elucidate the correlations between salivary IL-6 concentration and early locoregional recurrence in OSCC. METHODS: Stimulated saliva was collected before and after surgery from 27 consecutive patients with OSCC. Recurrence-free survival (RFS) curves were plotted using the Kaplan-Meier method. RESULTS: Of the 27 patients, 11 (41%) were diagnosed with locoregional recurrence within 24 months postsurgery. The median concentrations of IL-6 presurgery and postsurgery were 2.8 pg/mL and 2.1 pg/mL, respectively. The median postsurgery concentration of IL-6 was significantly higher in patients with than without locoregional recurrence (p = .02). Multivariate analysis revealed that postsurgery salivary IL-6 concentration was an independent risk factor for locoregional recurrence (p = .03; risk ratio, 0.14). CONCLUSIONS: Posttreatment concentration of salivary IL-6 may predict early locoregional recurrence in OSCC.

Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to elucidate changes in interleukin-6 (IL-6) levels in whole saliva during the treatment of patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN: Twenty-nine consecutive inpatients with OSCC were enrolled. Stimulated saliva was collected just after hospitalization (period 1), just before main treatment (surgery in 26 cases; period 2), and at the time of discharge (period 3). The mean intervals were 11+/-8 days between periods 1 and 2 and 30+/-18 days between periods 2 and 3. Nineteen age-matched healthy control subjects were also recruited. Interleukin-6 concentrations were measured by a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: Interleukin-6 was detected in 23 out of 29 samples in the OSCC group in period 1. The concentration of IL-6 was significantly higher in the OSCC group (mean 20.1+/-36.3 pg/mL) than in the control subjects (0.6+/-0.8 pg/mL; P=.003). The mean concentration of IL-6 at period 2 was 43.6+/-95.6 pg/mL, significantly higher than at period 1 (P=.002), and at period 3 was 17.1+/-27.6 pg/mL (P=.52 [compared with period 2]). CONCLUSIONS: Interleukin-6 was up-regulated in saliva in the OSCC patients. The IL-6 level tended to increase before treatment, and it returned to baseline levels after treatment.