Changes in nutritional status of patients with jaw deformities due to orthognathic surgery.

OBJECTIVE: In orthognathic surgery, it is important to carefully manage peri-operative nutrition because maxillomandibular fixation and problems such as swelling and pain after surgery may make it difficult to eat normally and may prevent adequate nutrition. This study investigated the changes in nutritional status of patients with jaw deformities due to orthognathic surgery. STUDY DESIGN: The subjects were 155 jaw deformity patients, who underwent orthognathic surgery. The nutritional status was evaluated using anthropometry immediately before and 10 days after surgery and clinical laboratory results and the controlling nutritional status (CONUT) score before surgery and immediately, 1 week and >6 months after surgery. We investigated the relationship among the nutritional status, surgical procedures, and dietary intake in patients who underwent orthognathic surgery. RESULTS: The surgical procedure time and amount of bleeding were significantly greater as the surgical procedure became more complex. All of the laboratory values and CONUT scores were significantly decreased immediately after surgery and then increased over time, recovering to the same level as before surgery except for serum albumin at >6 months after surgery. CONCLUSIONS: Nutritional management is considered as one of the key factors for the better and faster recovery after the orthognathic surgery.

Prognostic value of preoperative systemic inflammatory response as a prognostic indicator in patients with early-stage oral squamous cell carcinoma.

To determine the usefulness of lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and inflammatory response biomarker (IRB) score for predicting disease-specific survival and delayed cervical lymph node metastasis in early-stage oral squamous cell carcinoma (OSCC). We retrospectively analyzed 72 patients with early-stage OSCC. Receiver operating characteristic curve analysis was used to determine the cutoff values for LMR, NLR, and PLR. IRB score was determined as follows: high LMR, high NLR, and low PLR, which were each rated as 1. These scores were added to obtain IRB score (range: 0-3). From univariate analysis, gender, poor mode of invasion, and high IRB score were identified as significant risk factors for disease-specific survival. However, there were no independent factors for poor prognosis in multivariate analysis. On the other hand, for delayed cervical lymph node metastasis, poor mode of invasion, low LMR, high NLR, high PLR, and high IRB score were identified as significant risk factors from univariate analysis, and in multivariate analysis, poor mode of invasion and high IRB score were confirmed as independent risk factors. IRB score and mode of invasion are potentially independent risk factors for delayed cervical lymph node metastasis in early-stage OSCC.

Clinicopathologic factors influencing the screening accuracy of oral cytology: A retrospective cohort study.

Cytology is a simple and non-invasive screening method for oral cancer. However, this method is not yet routinely used by clinicians because of its high false negative rate (FNR) and due to lack of sufficient studies examining the factors for high FNRs. The present retrospective study aimed to compare the screening performance of conventional cytology (CC) and liquid-based cytology (LBC) through histological validation, and to elucidate factors inducing false negative screening in oral cytology. Cytological specimens with histological examination and intraoral digital images of the lesion were retrospectively collected between January 2017 and December 2018 for CC and between October 2019 and September 2021 for LBC. Oral cytological screening was conducted based on the oral Bethesda system for oral cytology. Clinical subtypes were re-evaluated using intraoral digital images. The screening accuracy of oral cytology was calculated considering the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting the malignant transformation of oral lesions. No statistically significant difference was noted in the inadequate rate between CC and LBC groups. For CC and LBC, the sensitivities were 60.9 and 59.2%, the specificities were 87.3 and 79.1%, the PPVs were 85.8 and 76.2%, and the NPVs were 63.9 and 63.2%, respectively. Thus, the screening accuracy was similar between methodologies. Among the clinicopathological factors investigated, histological diagnosis and cellularity contributed to false negative results. Homogeneous findings of oral epithelial dysplasia and the superficial growth of carcinoma in situ/squamous cell carcinoma resulted in false negative findings for CC and LBC. Furthermore, LBC samples with a lower cell number (<2,000 squamous cells) exhibited statistically significantly increased FNRs. The present study found that the cytological methods did not affect the inadequate rate and screening accuracy, whereas clinical subtype and cellularity decreased screening accuracy. Therefore, cytological screening and subsequent follow-up should be performed while considering clinical findings and the cellularity of cytology smears.

Melanotic neuroectodermal tumor of infancy in the mandible: A case report.

RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-ß/SOX9 axis in cancer progression.

Cancer-associated fibroblasts (CAFs) have important roles in promoting cancer development and progression. We previously reported that high expression of sex-determining region Y (SRY)-box9 (SOX9) in oral squamous cell carcinoma (OSCC) cells was positively correlated with poor prognosis. This study developed three-dimensional (3D) in vitro models co-cultured with OSCC cells and CAFs to examine CAF-mediated cancer migration and invasion in vitro and in vivo. Moreover, we performed an immunohistochemical analysis of alpha-smooth muscle actin and SOX9 expression in surgical specimens from 65 OSCC patients. The results indicated that CAFs promote cancer migration and invasion in migration assays and 3D in vitro models. The invading OSCC cells exhibited significant SOX9 expression and changes in the expression of epithelial-mesenchymal transition (EMT) markers, suggesting that SOX9 promotes EMT. TGF-ß1 signalling inhibition reduced SOX9 expression and cancer invasion in vitro and in vivo, indicating that TGF-ß1-mediated invasion is dependent on SOX9. In surgical specimens, the presence of CAFs was correlated with SOX9 expression in the invasive cancer nests and had a significant impact on regional recurrence. These findings demonstrate that CAFs promote cancer migration and invasion via the TGF-ß/SOX9 axis.

HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma.

Pontin and Reptin are closely related proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They form a hetero-oligomeric complex, Pontin/Reptin, which is involved in protein stability and assembly of the protein complexes as a molecular chaperone. Overexpression of Pontin and Reptin in tumor cells has been reported and is implicated in the development of various cancers. However, the molecular mechanism of Pontin/Reptin function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we identify HEAT repeat-containing protein 1 (HEATR1) as a novel binding factor of Pontin/Reptin. Functionally, HEATR1 stabilizes Pontin/Reptin and positively regulates OSCC cell proliferation by activating mTOR and pre-rRNA synthesis. We also find that HEATR1 expression is markedly upregulated in tumor region of OSCC tissue. Hence, we propose that HEATR1 is involved in the regulation of mTOR and ribosome biogenesis as a potential protein stabilizer of Pontin/Reptin in OSCC.

Vertical distraction osteogenesis of a reconstructed mandible with a free vascularized fibula flap: a report of two cases.

BACKGROUND: The free vascularized fibula flap presents many advantages such as sufficient length of the bony segment, good vascularization, better quality of the bone, and a long vascular pedicle, but it is also associated with some disadvantages with regard to prosthetic rehabilitation because of its limited height. Improvement in bone height is necessary for ideal dental implant treatment of reconstructed mandibles. CASE PRESENTATION: For two squamous cell carcinoma patients, mandibular bone reconstruction was performed secondarily with the peroneal flap after tumor resection. Since the bone height was insufficient at the time of implant treatment, occlusion reconstruction by dental implant was performed after vertical distraction osteogenesis. CONCLUSIONS: Vertical distraction osteogenesis is a suitable treatment option for alveolar ridge deficiency resulting from fibula transplantation for mandibular reconstruction following tumor surgery.

A simple technique for repositioning of the mandible by a surgical guide prepared using a three-dimensional model after segmental mandibulectomy.

BACKGROUND: Mandibular reconstruction is performed after segmental mandibulectomy, and precise repositioning of the condylar head in the temporomandibular fossa is essential for maintaining preoperative occlusion. METHODS: In cases without involvement of soft tissue around the mandibular bone, the autopolymer resin in a soft state is pressed against the lower border of the mandible and buccal and lingual sides of the 3D model on the excised side. After hardening, it is shaved with a carbide bar to make the proximal and distal parts parallel to the resected surface in order to determine the direction of mandibular resection. On the other hand, in cases that require resection of soft tissue around the mandible such as cases of a malignant tumor, right and left mandibular rami of the 3D model are connected with the autopolymer resin to keep the preoperative position between proximal and distal segments before surgical simulation. The device is made to fit the lower border of the anterior mandible and the posterior border of the mandibular ramus. The device has a U-shaped handle so that adaptation of the device will not interfere with the soft tissue to be removed and has holes to be fixed on the mandible with screws. RESULTS: We successfully performed the planned accurate segmental mandibulectomy and the precise repositioning of the condylar head by the device. CONCLUSIONS: The present technique and device that we developed proved to be simple and useful for restoring the preoperative condylar head positioning in the temporomandibular fossa and the precise resection of the mandible.

Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration.

Expression of keratin (K) 13 is replaced with that of K17 when squamous cells of the oral mucosa transform from normal and dysplastic epithelia to carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Since 14-3-3 sigma is functionally associated with K17, we examined possible relationships between expression of K17 and 14-3-3 sigma in oral CIS and SCC tissues by immunohistochemistry. We furthermore examined whether or not K17 expression or knockdown by small interfering RNA (siRNA) modulates the behavior of SCC cells in culture in terms of cell proliferation and migration. In tissue specimens of oral SCC and CIS, the pattern of cytoplasmic expression of 14-3-3 sigma and K17 was similar but neither was expressed in normal or dysplastic epithelia. Both proteins were demonstrated in the cytoplasm of control oral SCC ZK-1 cells, but expression of 14-3-3 sigma changed from cytoplasmic to nuclear upon knockdown of K17. In carcinoma cells, therefore, cytoplasmic localization of 14-3-3 sigma seems to accompany expression of K17. In K17-knockdown cells, proliferation was significantly suppressed at 4 days after seeding. In addition, the cell size of K17-knockdown cells was significantly smaller than that of control cells; as a result of which in the migration experiments, we found delayed closure of scratch wounds but migration as such was not affected. We conclude that K17 expression promotes SCC cell growth and cell size but does not affect cell migration. K17 expression is accompanied by cytoplasmic expression of 14-3-3 sigma, indicative of their functional relationship.

Autotransplantation or replantation of cryopreserved teeth: a case series and literature review.

BACKGROUND: The aim of this report was to evaluate the outcome of autotransplantation or replantation of cryopreserved teeth clinically and radiographically. Donor teeth were slowly frozen in a controlled-rate freezer using 5% dimethylsulfoxide (DMSO) and 6% hydroxyethyl starch (HES) as protectants. Seven cryopreserved teeth, with duration of storage ranging from 4 to 36 months, were autotransplanted or replanted at Niigata University Medical and Dental Hospital. Endodontic treatment involving root canal debridement followed by interim root canal filling with calcium hydroxide was started 3 weeks after the operation and continued with replacement of the calcium hydroxide filling at 2-week to 3-month intervals. Three transplants showed periodontal regeneration clinically and radiographically, whereas replacement root resorption was observed in the remaining transplants. From the results, it can be concluded that cryopreserved tooth autotransplantation has potential for clinical use; however, the risk of replacement root resorption remains.

Changes in overnight arterial oxygen saturation after mandibular setback.

Mandibular setback reduces space in the pharyngeal airway, and it has been suggested that it might induce sleep-disordered breathing. We report on its effects on space in the pharyngeal airway and respiratory function during sleep. We studied 78 patients (29 men and 49 women) in whom skeletal class III malocclusions had been corrected. The mean (range) age at operation was 24 (16-38) years and body mass index (BMI) 21.4 (16.1-30 .9)kg/m(2). Morphological changes were evaluated on lateral cephalograms taken three times: preoperatively, a few days postoperatively, and more than 6 months postoperatively. Overnight arterial oxygen saturation (SpO2) was measured by pulse oximetry 6 times: preoperatively, and on days 1, 3, 5, and 7, and 6 months postoperatively; oximetric indices were calculated. Those immediately after mandibular setback were significantly worse than those preoperatively, although they gradually improved. There were positive correlations between BMI and oximetric indices, and little association between changes in mandibular position and oximetric indices. There was no evidence of sleep-disordered breathing 6 months after mandibular setback because most patients adapt to the new environment for respiratory function during sleep. However, some (particularly obese) patients may develop sleep-disordered breathing just after mandibular setback. In such patients attention should be paid to respiratory function during sleep in the immediate postoperative period, and careful postoperative follow-up is needed.

Intraepithelially entrapped blood vessels in oral carcinoma in-situ.

It can be difficult to make a certain diagnosis in case of an oral borderline malignant lesion on hematoxylin-eosin-stained sections only. Furthermore, assessment of surgical margins of borderline lesions is difficult with the naked eye. We set out to determine the topographical distribution of capillary blood vessels within the epithelial zone and to assess its use as an aid for histopathological diagnosis and a framework for clinical assessment of lesional margins using optical techniques, such as narrow-band imaging (NBI) endoscopy. Capillary blood vessels entrapped in the epithelial compartment, which we have designated as intraepithelially entrapped blood vessels (IEBVs), were examined for their frequency, location, and shape in normal mucosa, dysplasia, and carcinoma in-situ (CIS) of the tongue using immunohistochemistry for CD31 and type IV collagen. When counted per unit length of epithelial surface, IEBVs increased in number significantly in CIS (5.6 ± 2.8), which was two times more than in normal (1.9 ± 1.6) and dysplastic (2.4 ± 1.5) epithelia. In addition, IEBVs in CIS had compressed shapes with occasional obstruction or collapse with hemorrhage and were arranged perpendicular to and extending up to the epithelial surface. These characteristic IEBVs in CIS were considered to be generated by complex expansion of rete ridges due to carcinoma cell proliferation within the limited epithelial space determined by the basement membrane. The recognition of IEBVs was helpful in the differential diagnosis of oral CIS, and the present data provide a valuable frame of reference for detecting oral CIS areas using such NBI-based optical devices.

Enhanced expression of podoplanin in oral carcinomas in situ and squamous cell carcinomas.

OBJECTIVE: Podoplanin, a known lymphatic endothelial cell marker, has been reported to be expressed in various types of cancer. To elucidate the expression of podoplanin in precancerous lesions, we examined the immunohistochemical profiles of podoplanin in oral squamous epithelial lesions. METHOD: We studied a total of 298 foci of squamous cell carcinoma (SCC), carcinoma in situ (CIS), epithelial dysplasia, and hyperplastic and/or normal epithelial lesions by immunohistochemistry using D2-40. RESULTS: There was no positivity for podoplanin in normal or hyperplastic epithelia, while all of the CIS and SCC foci stained positive. Approximately one third of the mild dysplasia foci (10 of 36 foci, 28%) and 80% of moderate dysplasia foci (78/98) showed grade 1 positive reactions (positive only in the 1st layer). Grade 2 reactions (up to 4th layer) were seen in 4 of 98 moderate dysplasia foci (4%), 29 of 74 CIS foci (39%), and 3 of 30 SCC foci (10%). Grade 3 reactions (to more than 5th layer) were found in 35 (47%) CIS foci and 26 (87%) SCC foci. CONCLUSIONS: The relationship between the present histological categorization and podoplanin grade was statistically significant. D2-40 expression is considered to be related to the severity of oral precancerous lesions.

Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ.

To evaluate differential expressions for keratin (K) subtypes 13 and 17 in oral borderline malignancies, we examined 67 surgical specimens of the oral mucosa for their immunohistochemical profiles. From those specimens, 173 foci of epithelial dysplasia, 152 foci of carcinoma in situ (CIS), and 82 foci of squamous cell carcinoma (SCC) were selected according to our diagnostic criteria, along with 20 areas of normal epithelia. In normal epithelia, there was no K17 positivity (0%), whereas definite K13 positivity (100%) was observed. The same tendencies were obtained in mild (undefined) and moderate (true) epithelial dysplasias (K17: 0%; K13: 100%). In contrast, all CIS (100%) had K17 positivities, while K13 positivities were lost in many of them (7%). Similar tendencies were confirmed in invasive SCC (K17: 100%, K13: 4%). Simultaneous immunopositivities for K17 and K13 were found only in SCC (7%) and CIS (4%) foci with distinct keratinization. These foci also showed K10 positivities, though K10 positive areas were not identical to K13 positive areas. The results indicate that expressions of K17 and K13 are reciprocal in oral epithelial lesions and that the K17 emergence is related to malignancies.