Yoshiki Nariai

Treatment modalities for oral verrucous carcinomas and their outcomes: contribution of radiotherapy and chemotherapy

AbstractBackground. This clinical study focused, firstly, on the results of treatment and, secondly, on the anaplastic transformation, of oral verrucous carcinomas (OVCs) diagnosed and treated from 1981 to 1997 at the Department of Oral and Maxillofacial Surgery at Shimane Medical University Hospital. Methods. We analyzed the treatment modalities and outcomes for 15 patients with OVC. Results. Excluding the results for 4 palliatively treated patients, the disease-free survival rates of the patients after the initial treatments, were 82% at 5 years and 66% at 10 years; for all 15 patients, these rates were 57% and 46%, respectively. Surgery alone and surgery combined with other treatments (such as radiotherapy and chemotherapy) appeared to yield disease-free survival rates to those achieved superior with other treatments whether single or combined; (78% vs 33% for 5-year disease-free survival; 52% vs 33% for 10-year disease-free survival); however, the difference was not significant (P = 0.47). Well differentiated squamous cell carcinomas (W-SCCs) (n = 5) as well as spindle cell carcinoma (n = 1) were found in subsequent operative or biopsy specimens. Conclusion. Surgery was the most reliable treatment method for OVC; however, radiotherapy combined with chemotherapy was the next most preferable treatment when surgery was not undertaken. We also found that highly malignant transformation (anaplastic transformation) occasionally occurred during treatments for OVC.

Carboplatin induces Fas (APO-1/CD95)-dependent apoptosis of human tongue carcinoma cells: sensitization for apoptosis by upregulation of FADD expression.

We examined the apoptosis of tongue carcinoma cells and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA) induced apoptosis of SCC‐9 and SCC‐25, human well‐differentiated tongue squamous carcinoma cell lines. Neutralizing anti‐Fas (APO‐1/CD95) and anti‐Fas ligand (FasL) antibodies obliterated the CBDCA‐induced cell death. In the absence of CBDCA, cytotoxic anti‐Fas antibody, which binds to and activates Fas at the cell surface, failed to induce apoptosis. However, in the presence of CBDCA, the cytotoxic antibody markedly enhanced the apoptosis in a dose‐dependent manner. Western blotting and reverse‐transcription (RT) PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC‐25 induced apoptosis of Jurkat cells, Fas‐sensitive T‐lymphatic leukemia cell line, and the apoptosis was inhibited by neutralizing anti‐Fas or anti‐FasL antibody. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional FasL, which by themselves fail to induce apoptosis. The expression of FADD in the tongue carcinoma cells was very low and was largely enhanced by CBDCA treatment. Suppression of FADD expression using the specific antisense oligonucleotide resulted in a failure of CBDCA induction of cell death. These results indicate that a deficiency of FADD is involved in the insensitivity of tongue carcinoma cells for Fas activation, and that CBDCA treatment switches nonfunctional Fas to functional Fas by upregulation of FADD expression, resulting in activation of a Fas‐sensitive pathway leading to apoptosis.

Oral symptoms including dental erosion in gastroesophageal reflux disease are associated with decreased salivary flow volume and swallowing function

BackgroundThis preliminary clinical study aimed to evaluate the effects of salivary flow volume and swallowing function on oral symptoms including dental erosion in gastroesophageal reflux disease (GERD).MethodsThe subjects were 40 GERD patients and 30 (15 younger, 15 older) healthy controls. Detailed medical, dietary, and dental histories were obtained to identify individual behavioral habits potentially associated with dental erosion. Oral examination evaluated dental erosion and determined scores for the decayed, missing, filled (DMF) index, the papillary, marginal, attached (PMA) index for gingivitis, and the Simplified Oral Hygiene Index (OHI-S). Salivary flow volume and swallowing function were evaluated by the Saxon test and repetitive saliva swallowing test, respectively.ResultsThe DMF index and OHI-S scores differed significantly between all 3 groups. The PMA index was significantly different between the GERD group and the two control groups. The prevalence of dental erosion was 24.3% in the GERD group (0% in the control groups). No specific relationship was found between the incidence of dental erosion and dietary history or behavioral habits. The Saxon test results were significantly lower in the GERD group than in both the control groups. Frequency of swallowing was significantly lower and time to first swallow was significantly longer in the GERD group than in the two control groups.ConclusionsOral symptoms in GERD are likely to be associated with impaired salivary flow volume or swallowing function. Treatment for the oral dryness induced by reduced salivary flow volume and rehabilitation for swallowing function could be indicated in patients with GERD.

Applicability of buccal fat pad grafting for oral reconstruction

This study evaluated the applicability of pedicled buccal fat pad grafting for the reconstruction of defects surgically created during oral surgery. A buccal fat pad graft was applied in 23 patients (5 males, 18 females; mean age 68.3 years) between 2003 and 2011. The graft was used to cover surgical defects of the palate, maxilla, upper gingiva, buccal mucosa, lower gingiva, oral floor, and temporomandibular joint region. Size of the surgical defects ranged from 15mm×12mm to 30mm×40mm; size of the buccal fat pad ranged from 15mm×12mm to 43mm×38mm. A pedicled buccal fat pad was prepared by incising the maxillary vestibule following primary surgery, and the surrounding connective tissue was preserved to supply nutrition to the pedicle during surgery. The buccal fat pad was placed on the raw surface of soft tissue or bone surface and sutured to the surrounding tissue of the defect. Complete epithelialization was observed within 4 weeks postoperatively. There were no complications or functional disorders during follow-up. Buccal fat pad grafting appears to be feasible for the reconstruction of surgically induced defects, and can be extended to the palate, mandible, mouth angle, and temporomandibular joint region.

The retromandibular transparotid approach for reduction and rigid internal fixation using two locking miniplates in mandibular condylar neck fractures

We evaluated the safety, efficacy, and morbidity associated with the treatment of displaced mandibular condylar neck fractures using a retromandibular transparotid approach to reduce and rigidly fix using two 2.0-mm locking miniplates. Our surgical inclusion criteria were: patient selection of open reduction and fixation, displaced unilateral condylar fractures with derangement of occlusion, and bilateral condylar fractures with an anterior open bite. The study group consisted of 19 patients who underwent surgery for 19 mandibular condylar neck fractures; patients were analyzed prospectively, with more than 6 months of follow-up, and were evaluated in terms of functional results, scar formation, postoperative complications, and stability of fixation. The results showed that functional occlusion identical to the preoperative condition and correct anatomical reduction of the condylar segments in centric occlusion, followed by immediate functional recovery, was achieved in all patients. No patient suffered from any major or permanent complication postoperatively, although there were two cases (11%) of temporary facial nerve palsy, which resolved completely within 3 months. Surgical scars were barely visible. The retromandibular transparotid approach with open reduction and rigid internal fixation for displaced condylar neck fractures of the mandible is a feasible and safe, minimally invasive surgical technique that provides reliable clinical results.

FAP-1 and NF-κB expressions in oral squamous cell carcinoma as potential markers for chemo-radio sensitivity and prognosis.

This study was designed to investigate the feasibility of using Fas-associated phosphatase-1 (FAP-1), nuclear factor kappa B (NF-κB) and p53 as markers for chemo-radio sensitivity in oral squamous cell carcinoma (OSCC). FAP-1 plays a role as an anti-apoptotic factor through Fas-dependent apoptosis after chemo-radiotherapy. NF-κB and p53 might be involved in modulation of FAP-1 expression. FAP-1, NF-κB and p53 expression were immunohistochemically examined using biopsy specimens in 50 OSCC patients treated with chemotherapy and/or radiotherapy. FAP-1 was expressed in 52%, NF-κB in 52% and p53 in 46% of patients. There was no significant difference in FAP-1, p53 or NF-κB expression according to the clinicopathological features. No correlation was found among FAP-1, p53 or NF-κB expression. FAP-1-positive cases showed a poorer survival rate than FAP-1-negative cases (P = 0.0409) and NF-κB-positive cases showed a poorer survival rate than NF-κB-negative cases (P = 0.0018). Multivariate analysis showed that FAP-1 expression, NF-κB expression, clinical stage and age were significant independent variables for survival (clinical stage: P = 0.0016; age: P = 0.0016; NF-κB: P = 0.0314; FAP-1: P = 0.0366). These results suggest that FAP-1 and NF-κB might play a role as chemo-radioresistant factor during chemo-radiotherapy, and FAP-1 and NF-κB expression in OSCC would be feasible markers for chemo-radio sensitivity and prognosis.

Effects of transforming growth factor beta 1 on the plasminogen activation system, collagen and integrin synthesis, and proliferation of rabbit mandibular condylar chondrocytes

The objective of this study was to identify the mechanism by which mandibular condyle chondrocytes regulate the extracellular matrix. Primary rabbit condylar chondrocytes were isolated, cultured, and treated with transforming growth factor beta 1 (TGF-β1). Cells were then assayed for the following: urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1), collagen types I and II, β1 integrin expression, and proliferative activity. TGF-β1 induced synthesis of collagen type II, αVβ1 integrin, and PAI-1. TGF-β1 induced the growth of chondrocytes and suppressed the synthesis of uPA. Chondrocyte regulation of the extracellular matrix is mediated by TGF-β1. Synthesis of collagen type II, αVβ1 integrin, and PAI-1 is induced, while uPA is suppressed. Also, TGF-β1 induces cellular growth.

Simultaneous Sinus Lifting and Alveolar Distraction of a Severely Atrophic Posterior Maxilla for Oral Rehabilitation with Dental Implants

We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants) were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n = 4). A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80) after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation.

Histopathological Features of Secondary Squamous Cell Carcinoma Around a Dental Implant in the Mandible After Chemoradiotherapy: A Case Report With a Clinicopathological Review.

Oral squamous cell carcinoma (OSCC) around a dental implant is a rare pathologic condition. This report describes a case of recurrent OSCC surrounding a dental implant, histopathologic findings, and a literature review of this condition. A 58-year-old Japanese woman underwent chemoradiotherapy for OSCC in the right lower gingiva, resulting in a complete response. Nine years after primary chemoradiotherapy, a dental implant was placed in her atrophic mandible. Three years later, an OSCC developed around the dental implant in the right lower premolar region. Marginal mandibulectomy was performed. Microscopic examination showed medullary invasion around the implant surface, suggesting that tumor infiltration of the bone was through the interface between the implant and bone. However, no downward invasion through the interface was evident. OSCC can develop around dental implants that are placed for oral rehabilitation after ablative surgery. Staging of OSCC and planning of surgical management should be carried out carefully, because implants placed adjacent to the OSCC can influence tumor invasion. A high degree of vigilance for OSCC is required during follow-up of patients with dental implants who have OSCC risk factors such as premalignant lesions. Detailed evaluation, including biopsy examination, is essential for distinguishing peri-implantitis from OSCC.

Surgical treatment of comminuted mandibular fractures using a low-profile locking mandibular reconstruction plate system.

Objective: The treatment of comminuted mandibular fractures is challenging due to the severity of associated injuries and the need for a careful diagnosis with adequate treatment planning. Recently, open reduction and stable internal fixation (OR-IF) with a load-bearing reconstruction plate have been advocated for reliable clinical outcomes with minimal complications. This clinical prospective study evaluated OR-IF in the surgical management of comminuted mandibular fractures with a new low-profile, thin, mandibular locking reconstruction plate. Materials and Methods: We prospectively assessed OR-IF of comminuted mandibular fractures with a low-profile locking mandibular reconstruction plate in 12 patients (nine men, three women; mean age 32.2 [range 16-71] years) between April 2010 and December 2011. The clinical characteristics and associated clinical parameters of patients were evaluated over a minimum follow-up period of 12 months. Results: Traffic accidents caused 50% of the fractures, followed by falls (25%). Four patients (33.3%) had associated midfacial maxillofacial fractures, while five patients had other mandibular fractures. Seven patients (58.3%) needed emergency surgery, mostly for airway management. Anatomical reduction of the comminuted segments re-established the mandibular skeleton in stable occlusion with rigid IF via extraoral (33.3%), intraoral (50%), or combined (16.7%) approaches. Immediate functional recovery was achieved. Sound bone healing was confirmed in all patients, with no complications such as malocclusion, surgical site infection, or malunion with a mean follow-up of 16.3 (range 12-24) months. Conclusions: OR-IF using a low-profile reconstruction plate system is a reliable treatment for comminuted mandibular fractures, enabling immediate functional recovery with good clinical results.