Development of prediction models for the sensitivity of oral squamous cell carcinomas to preoperative S-1 administration.

S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance.

[Effective Treatment of Ameloblastoma in an Odontogenic Cyst with Fenestration before Curative Surgery-A Case Report].

Ameloblastoma is a benign odontogenic tumor that rarely undergoes malignant transformation and metastasis but may be locally invasive and recurrent. Fenestration is used to reduce maxillary odontogenic cysts. Here, we report a case ofameloblastoma that developed in the wall of an odontogenic cyst and was treated with fenestration before curative surgery. A 57-yearold Japanese man presented with a mass on the right side ofthe lower gingiva. Computed tomography revealed a unicystic lesion in the right mandibular body, accompanied by a multicystic area in the right lower canine region. Three involved molars were extracted and the cystic wall was harvested. Biopsy analysis revealed an odontogenic cyst in the unicystic lesion and an ameloblastoma in the multicystic area. The ameloblastoma was thought to have developed in the odontogenic cyst wall. The biopsy wound was maintained as a fenestration for 3 months and the lesion was reduced. Marginal resection of the mandible with cystectomy was performed to preserve mandibular bone continuity and the mandibular nerve. Although fenestration delayed curative surgery, the large cystic lesion reduction helped to avoid complications after curative surgery.

Overview of innovative advances in bioresorbable plate systems for oral and maxillofacial surgery.

Maxillofacial osteosynthetic surgeries require stable fixation for uneventful boney healing and optimal remodeling. Although conventional titanium plates and screws for osteofixation are considered the gold standard for rigid fixation in maxillofacial surgeries, bioresorbable implants of plates and screw systems are commonly used for various maxillofacial osteosynthetic surgeries such as orthognathic surgery, maxillofacial fractures, and reconstructive surgery. Titanium plates are limited by their palpability, mutagenic effects, and interference with imaging, which may lead to the need for subsequent removal; the use of a biologically resorbable osteofixation system could potentially address these limitations. However, several problems remain including fundamental issues involving decreased mechanical strength and stability, slow biodegradation, complex procedures, and the available bioresorbable implant materials. Major advances in bioresorbable plate systems have been made with the use of bioactive/resorbable osteoconductive materials and an accelerator of bioresorption, such as polyglycolic acid. This report presents an overview of currently available resorbable implant materials and their applications, with a focus on recent innovative advances and new developments in this field.

Expression of aquaporin 3 and 5 as a potential marker for distinguishing dry mouth from Sjögren's syndrome.

A study was performed to investigate whether expression of aquaporin (AQP) 3 and 5 has potential as a marker for distinguishing dry mouth from Sjögren's syndrome. Twenty-five patients underwent labial minor salivary gland biopsy (dry mouth, n = 9; Sjögren's syndrome, n = 16; control, n = 8). All patients were interviewed about their medical history and subjective oral symptoms, and intraoral examinations were conducted. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to examine the expression and localization of AQP3 and 5. Significant differences in oral dryness, dry eye, medical history, and Saxon test results were revealed among the groups. However, there were no significant inter-group differences in expression of mRNA for AQP3 and 5. Immunohistochemical staining for AQP3 was localized mainly in the basolateral and part of the ductal cell membrane, and was barely evident in the apical membrane of acinar cells. AQP5 was localized to the basolateral and apical membrane and cytoplasm, but not the ductal cell membrane. Staining intensity for AQP3 in the apical membrane was significantly stronger in Sjögren's syndrome, and that for AQP5 was significantly weaker in dry mouth. Taken together, the present data suggest that expression of AQP3 and 5 may be a marker for distinguishing between patients with dry mouth and those with Sjögren's syndrome.

Fracture of the Clavicle following Radical Neck Dissection and Reconstruction Using Pectoralis Major Myocutaneous Flap Accompanied by Postoperative Radiotherapy.

Fracture of the clavicle following radical neck dissection (RND) and/or radiotherapy is a rare complication. Several causes of fracture of the clavicle after treatment of head and neck cancer were postulated in previous reports. We present a case of fracture of the clavicle after treatment of squamous cell carcinoma of the tongue. An 81-year-old Japanese woman underwent RND, subtotal glossectomy, reconstruction using a pectoralis major myocutaneous flap (PMMCF), and postoperative radiotherapy (50.4 Gy). One month after the primary treatment, fracture of the clavicle occurred. It was thought that muscular dynamic factor and reduction of blood supply in the clavicle associated with RND and PMMCF were the causes of the fracture. We have to recognize the occurrence of this complication and try to reduce the factors related to the complication.

[Surgical Procedure of Buccal Mucosal Carcinoma - Reconstruction of Mouth Angle].

Surgical resection of the buccal mucosal carcinoma often induces soft tissue defect. The treatment plan should be considered to preserve oro-facial function and morpho-esthetics. This retrospective study reports the surgical reconstruction procedures in buccal mucosal carcinoma patients. We evaluated 4 cases(2 men, 2 women, mean age: 81.8 year-old)treated in Department of Oral and Maxillofacial Surgery, Shimane University Hospital between June 2007 and January 2017. The average size of primary tumor was 4.9 cm2. And the average size of facial skin defect in the mouth angle was 3.1 cm2. The facial local skin flaps and/or other pedicled flap were used for the reconstruction of the mouth angle. Severe contraction of the scar was manifested in 2 cases. Though reconstruction using the local pedicled flaps for full thickness skin defect in the mouth angle would be feasible, special attention is considered regarding the postoperative contraction of the scar.

[A Case of Medical Leech Therapy for Venous Congestion Following Forearm Flap Reconstruction].

Leeches have been used for medical treatment for at least 2,500 years. Plastic surgeons have recently begun to use leeches to reduce venous congestion after flap reconstruction. However, few reports of leech use in the oral region have been published. We report a case of medical leech therapy used to treat venous congestion after forearm flap reconstruction for oral cancer. A 67-year-old female was diagnosed with squamous cell carcinoma of the left tongue margin(cT2N0M0, Stage Ⅱ). The patient underwent tracheostomy, supraomohyoid neck dissection, hemiglossectomy, and reconstruction using a free forearm flap under general anesthesia. Venous congestion in the forearm flap was detected 21 hours postoperatively, and reanastomosis of the flap was performed. However, venous congestion continued after revision surgery. Therefore, we introduced medical leech therapy to treat the venous congestion. Leeches were used twice daily for 5 days, and the total hematophagy volume was 21.6 g. After leech treatment, continuous bleeding from the skin flap decreased and skin color improved. The medial skin flap survived, and the patient was able to eat 13 days after the initial operation. The rest of the treatment has been uneventful to date without dysfunction of the skin flap.

[Feasibility of a Heart-Shaped Modified Pectoralis Major Myocutaneous Flap for a Stabilized Vascular Supply in the Reconstruction of Surgically Induced Defects in Patients with Advanced Oral Cancer].

The pedicled pectoralis major myocutaneous(PMMC)flap, used for the reconstruction of surgical defects in advanced oral cancer resection, is versatile and can be obtained without a highly-invasive procedure. However, flap utility is limited by an unstable blood supply and the relatively high rate of partial necrosis of the skin island. Thus, the use of microvascularized free flaps has become more common in patients requiring oral-maxillofacial reconstruction. Detailed angiographic studies revealed the 3-dimensional vascular anatomy of the PMMC flap. This allowed us to obtain a modified, heart-shaped flap with a skin island that includes the intramuscular vascular networks between the pectoral branches of the thoracoacromial vessels and the intercostal perforators of the internal mammary vessels, thus ensuring a sufficient blood supply and stable survival of the flap. We have used this technique since 2015 to treat 7 patients with locally advanced or recurrent(salvage)oralcancer. None developed critical flap problems, and survival of the total skin island was successfully obtained in all cases. Transfer of the heart-shaped PMMC, including the multiple intercostal perforators from the internal mammary vessels, may contribute to a stable blood supply of the skin island and therefore can be effective for advanced oral cancer reconstruction.

[Clinicopathological Study of the Resected Oral Leukoplakia Cases].

Oral leukoplakia is the most common premalignant or potentially malignant lesion in the oral mucosa. This retrospective study examined 67 lesions from 62 patients with clinical diagnoses of oral leukoplakia who underwent surgical excision in our department from 2015 to 2017. The patients comprised 22 men and 40 women. The most common location of the lesion was the lower gingiva, followed by the tongue, upper gingiva, buccal mucosa, palate, and lip. The most common clinical type was the white-spotted, followed by erythroleukoplakia, hillock, and verrucous types. Histopathologically, 16 lesions were oral intraepithelial neoplasia, whereas five were squamous cell carcinoma. The data identified several characteristics of oral leukoplakia that predict a high risk of malignant transformation and require aggressive surgical resection.

Oral microbiome alterations of healthy volunteers with proton pump inhibitor.

BACKGROUND AND AIM: Acid suppressive agents including proton pump inhibitors (PPIs) are used as first-line treatment for various acid-related gastrointestinal disorders. Although known to profoundly reduce gastric acid production, their influence on inhibition of acid secretion as part of the function of the gastrointestinal tract microbiome remains to be elucidated. The aim of the present study was to examine the effects of PPI usage on oral and gut microbiota in healthy volunteers. METHODS: Ten healthy adult volunteers receiving no medications were enrolled. We obtained fecal, saliva, and periodontal pocket fluid samples from the subjects before and after 4 weeks of once daily administrations of 20-mg esomeprazole. The effects of PPI administration on bacterial communities were investigated using a 16S rRNA gene sequencing method. RESULTS: Species richness (alpha diversity) was significantly different among the salivary, periodontal pocket, and fecal samples. Furthermore, the measurements for UniFrac distances, despite inter-individual variations (beta diversity), of the microbiota structure of saliva and periodontal pocket and feces samples were clearly separated from each other. The salivary samples showed significant differences between alpha and beta diversity measurements before and after administration of the PPI for 4 weeks. Meanwhile, taxon-based analysis indicated that PPI administration raised the ratio of Streptococcus organisms in fecal samples, suggesting a potentially unfavorable effect leading to gut microbiota alteration. Moreover, alterations of the microbiota in the oral carriage microbiome along with bacterial overgrowth (Streptococcus) and decreases in distinct bacterial species (Neisseria and Veillonella) were observed. CONCLUSIONS: These results suggest that PPIs cause both oral and gut microbiota alterations.

Oral soft tissue disorders are associated with gastroesophageal reflux disease: retrospective study.

BACKGROUND: Dental erosion (DE), one of oral hard tissue diseases, is one of the extraoesophageal symptoms defined as the Montreal Definition and Classification of gastroesophageal reflux disease (GERD). However, no study evaluated the relationship between GERD and oral soft tissues. We hypothesized that oral soft tissue disorders (OSTDs) would be related to GERD. The study aimed to investigate the association OSTDs and GERD. METHODS: GERD patients (105 cases), older and younger controls (25 cases each) were retrospectively examined for oral symptoms, salivary flow volume (Saxon test), swallowing function (repetitive saliva swallowing test [RSST]), teeth (decayed, missing, and filled [DMF] indices), and soft tissues (as evaluation of OSTDs, gingivitis; papillary, marginal, and attached [PMA] gingival indexes, simplified oral hygiene indices [OHI-S], and inflammatory oral mucosal regions). Clinical histories, which included body mass index [BMI], the existence of alcohol and tobacco use, and bruxism, were also investigated. A P value of <0.05 was defined as statistically significant. RESULTS: GERD patients, older and younger controls participated and aged 66.4 ± 13.0, 68.3 ± 8.2 and 28.7 ± 2.6 years old, respectively. The most common oral symptom in the GERD patients was oral dryness. Salivary flow volume and swallowing function in the GERD patients were significantly lower than in either of the controls (all P < 0.05). Inflammatory oral mucosal regions were found only in the GERD patients. The DMF indices, as a measure of dental caries, in the GERD patients were higher than in the younger controls (P < 0.001), but lower than in the older controls (P = 0.033). The PMA gingival indexes, as a measurement for gingival inflammation, and OHI-S, as a measure for oral hygiene, in the GERD patients were significantly higher than in either of the controls (all P < 0.05). Though no significant differences in BMI, the existence of alcohol and tobacco use were found, bruxism, as an exacerbation factor of periodontal disease, in the GERD patients was significantly more frequent than in either control group (P = 0.041). CONCLUSIONS: OSTDs were associated with GERD, which was similar to the association between DE and GERD.

Diagnostic accuracy of oral cancer cytology in a pilot study.

BACKGROUND: Recently, cytology has been applied to the diagnosis of oral lesions. We aimed to explore the diagnostic accuracy of oral cytology based on the histological diagnosis. METHODS: Histological diagnoses of 327 cases were classified as Negative, Borderline lesion -, Borderline lesion +, oral intraepithelial neoplasia/carcinoma in situ (OIN/CIS), or Positive. Cytological diagnoses were classified as NILM (negative for intraepithelial lesion or malignancy), LSIL (low-grade squamous intraepithelial lesion), HSIL (high-grade squamous intraepithelial lesion), or SCC (squamous cell carcinoma). The cytology slides were evaluated by 10 raters and the results were compared with the histology results. RESULTS: In 142 cases that were histologically negative, the number of NILM, LSIL, HSIL, and SCC and other malignancy was 77 (54.2%), 47 (34.3%), 8 (5.6%), and 10 (7.0%), respectively. Among 32 cases of Borderline lesion -, the number of NILM, LSIL, HSIL, and SCC and other malignancy was 11 (34.3%), 11 (34.3%), 9 (28.1%), and 1 (3.1%), respectively. Also, in 4 cases of Borderline lesion +, the number of NILM, LSIL, HSIL, and SCC and other malignancy was 2 (50.0%), 0 (0.0%), 0 (0.0%), 2 (50.0%), respectively. Among 12 cases of OIN/CIS, the number of NILM, LSIL, HSIL, and SCC and other malignancy was 1 (8.3%), 2 (16.7%), 4 (33.3%), and 5 cases (41.7%), respectively. Among 137 cases with a histological diagnosis of Positive, the number of NILM, LSIL, HSIL, and SCC and other malignancy was 7 (5.1%), 22 (16.1%), 19 (13.9%), and 89 (65.0%), respectively. Sensitivity, specificity, and positive predictive and negative predictive values were 93.5, 50.6, 62.4, and 89.8%, respectively, when the cytological diagnosis of Negative was assumed to be NILM; they were 77.8, 83.9, 81.0 and 81.1%, respectively, if the cytological diagnosis of Negative was assumed to be NILM and LSIL. The number of false-positive and false-negative diagnosis affected cases with LSIL and HSIL may indicate the difficulty in the cytological diagnosis of borderline lesions. While the negative predictive value was relatively high (89.8%) when cytological Negative was assumed to be NILM only. CONCLUSION: Histopathological examination should be recommended in cases with cytological diagnoses of LSIL, HSIL, and SCC.

G196 epitope tag system: a novel monoclonal antibody, G196, recognizes the small, soluble peptide DLVPR with high affinity.

The recognition specificity of monoclonal antibodies (mAbs) has made mAbs among the most frequently used tools in both basic science research and in clinical diagnosis and therapies. Precise determination of the epitope allows the development of epitope tag systems to be used with recombinant proteins for various purposes. Here we describe a new family of tag derived from the epitope recognized by a highly specific mAb G196. The minimal epitope was identified as the five amino acid sequence Asp-Leu-Val-Pro-Arg. Permutation analysis was used to characterize the binding requirements of mAb G196, and the variable regions of the mAb G196 were identified and structurally analyzed by X-ray crystallography. Isothermal titration calorimetry revealed the high affinity (Kd = 1.25 nM) of the mAb G196/G196-epitope peptide interaction, and G196-tag was used to detect several recombinant cytosolic and nuclear proteins in human and yeast cells. mAb G196 is valuable for developing a new peptide tagging system for cell biology and biochemistry research.

[A Contrivance for Closure and Dressing of Orocutaneous Fistula Developed in Advanced Oral Cancer].

Orocutaneous fistula sometimes occurs in locallyadvanced unresectable or recurrent oral squamous cell carcinoma. The developed orocutaneous fistula results in constant leakage of saliva, ingested foods and liquids and decline in patients' quality of life(QOL). A 47-year-old Japanese man had received treatment for tongue carcinoma. At the routine follow-up, a cystic lesion in the right submandibular region was detected. Biopsyof the specimen of the cystic lesion revealed squamous cell carcinoma. After chemotherapy, an orocutaneous fistula between the right oropharyngeal and the right submandibular region developed and graduallyincreased. Although closure and dressing of the orocutaneous fistula with various materials was attempted, it was ultimatelyunsuccessful. Finally, application of a rubber film and silicone adhesive agent to the skin was successful for closure and dressing of the fistula. Orocutaneous fistula is one of major contributors to decline in patients' QOL. The sharing of information regarding effective methods or materials for closure and dressing of orocutaneous fistula is necessaryto maintain patients' QOL.

[A Patient with Lower Lip Verrucous Carcinoma Treated with a Tongue Flap for Functional and Esthetic Reconstruction].

Surgery is generally indicated for the treatment of lower lip carcinoma. However, surgery can lead to esthetic as well as functional issues, with disturbances in eating and articulation. If the defect involves less than one-third of the width of the lower lip, primary closure is possible. If the defect is wider, reconstructive local flaps may be necessary for both esthetic and functional recovery. This report describes a case of lower lip verrucous carcinoma in which a tongue flap was used to treat a defect involving more than half the width of the lower lip following resection. The patient was a 91-year-old woman who complained of lower lip discomfort. A biopsy revealed verrucous carcinoma, and we performed resection. After a 3-week waiting period, we performed secondary tongue flap reconstruction. Satisfactory function and cosmetic results were achieved.

[Applicability of Pedicled Coronoid Process and Temporal Muscle(Fascial)Combined(PCPTM)Flap for Reconstruction of Orbital Floor Defect Following Hemi-Maxillectomy for Advanced Maxillary Cancer - A Report of Two Cases].

We usually perform surgery for resectable oral and maxillofacial carcinomas. Following complete cancer resection, reconstruction of soft and hard tissues using various types of local flaps and/or vascularized free flaps is usually performed. The maxilla is composed of various anatomical structures. In particular, reconstruction of the orbit is one of the most important and challenging procedures for prevention of functional and esthetic complications. Here we report 2 cases of orbital floor defect reconstruction following advanced maxillary cancer resection using a pedicled coronoid process and temporal muscle (fascial)combined(PCPTM)flap. Case 1: A 69-year-old Japanese man with squamous cell carcinoma of the left maxilla (cT4aN2bM0, Stage IV A). Case 2: An 86-year-old Japanese woman with recurrence of myoepithelial carcinoma of the left maxilla. In both cases, the orbital floor defect was reconstructed following hemi-maxillectomy using a PCPTM flap. Minor infection and/or partial necrosis were observed postoperatively, and a maxillofacial prosthesis was used in one case. A PCPTM flap was feasible for reconstruction of surgical defects of the orbital floor following maxillectomy for cancer.

Does a Retromandibular Transparotid Approach for the Open Treatment of Condylar Fractures Result in Facial Nerve Injury?

PURPOSE: The retromandibular transparotid approach (RMA) to condylar fractures of the mandible provides excellent access, but can increase the risk of complications. The aim of this study was to estimate the frequency of facial nerve paralysis (FNP) and associated postoperative complications after open reduction and rigid internal fixation (ORIF) of subcondylar fractures through the RMA. MATERIALS AND METHODS: This was a retrospective cohort study of patients with condylar fractures requiring ORIF through the RMA. The inclusion criteria were 1) a medical record of surgical treatment of a subcondylar fracture by RMA; 2) preoperative and postoperative radiographs; 3) mental status permitting an adequate neuromotor examination; 4) absence of a post-injury or pretreatment functional facial nerve deficit; and 5) regular postoperative follow-up longer than 6 months with documentation of complications, functional results, and fixation stability. The predictive variables were age, gender, fracture site, fracture pattern, concomitant fractures, etiology, and plate types. The outcome variable was FNP. Univariate, bivariate, and multiple logistic regression statistics were computed. RESULTS: Fifty patients with 55 displaced mandibular subcondylar fractures (35 men, 15 women; mean age, 44.5 yr; range, 17 to 87 yr) met the inclusion criteria. The condylar fracture involved the neck in 35 patients (63.6%) and the base in 20 patients (36.4%). The fracture pattern was deviation in 11 patients (20.0%), displacement in 23 (41.8%), and dislocation in 21 (38.2%). Precise ORIF with double-buttress fixation resulted in immediate functional recovery in all patients. Seven fractures (12.7%) were associated with FNP that resolved completely within 6 months. Further statistical analysis showed that dislocated and displaced condylar neck fractures were significant risk factors for postoperative FNP (P < .05). Other postoperative complications were minimal. CONCLUSION: The RMA for subcondylar fractures is feasible and safe. Dislocated condylar neck fractures are associated with a highly increased risk of temporary postoperative FNP as a surgical complication.

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.

Clinical Features and Treatment Modes of Mandibular Fracture at the Department of Oral and Maxillofacial Surgery, Shimane University Hospital, Japan.

BACKGROUND: The number of elderly patients with maxillofacial trauma is rapidly increasing due to active lifestyles and longevity. Shimane prefecture has the fastest growing proportion of elderly individuals in Japan. The aim of this study was to reveal the distinctive features and treatment modes of mandibular fracture treatment mode in patients requiring hospitalization at the Department of Oral and Maxillofacial Surgery, Shimane University Hospital, Japan. PATIENTS AND METHODS: Patient age, sex, period between injury and first consultation, years since injury, cause of injury, fracture site, treatment, and duration of hospitalization were evaluated. Univariate Poisson regression, relative risk with 95% confidence interval based on the Wald test, Fisher's exact test, and Kruskal-Wallis test were used to explore associations among clinical and demographic variables. RESULTS: In total, 305 patients were diagnosed with and hospitalized for mandibular fracture from 1980 to 2010. Younger age increased the risk for mandibular fracture. Incidence was higher in males than females, particularly in the young, but the male to female ratio decreased with age. The period until first hospital consultation decreased progressively over the study period. Fall was a much more frequent cause in patients aged ≥60 than in those aged <60 years. Mandibular fracture with condyle, symphysis, and angle involvement were most common and were associated with sex, age, and treatment mode. Length of hospitalization has decreased since 1980. CONCLUSION: In our department, patients aged ≥60 years accounted for a greater proportion of mandibular fracture cases than in many previous studies, reflecting the greater proportion of elderly residents in Shimane prefecture.

Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma.

BACKGROUND: Oral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC. METHODS AND FINDINGS: The study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients' pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11-1.28], p < 0.001) and NAC1 IRI (0.78 [0.68-0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ≤ 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC. CONCLUSIONS: NAC1 has potential as a marker for distinguishing OED from CIS/OSCC.