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Introduction SO-1105 is an oral mucosal adhesive tablet containing 50 mg of miconazole. It had been shown overseas that a once-daily application of the drug continues antifungal effect in the treatment of oropharyngeal candidiasis. We report the results of the phase 3 clinical study of this drug with miconazole gel as a control in Japan. Methods The study included patients aged 20 years or older with oropharyngeal candidiasis who had oral lesions characterized by oropharyngeal candidiasis and whose fungi was confirmed by direct microscopic examination. The primary efficacy endpoint was the clinical cure rate on Day15 after 14 days of administration. The population analyzed for efficacy was per protocol set (PPS). Results 120 subjects were included in PPS. In detail, 59 subjects were in the SO-1105 group (SO-1105 group) and 61 subjects were in the miconazole gel group (Gel group). For efficacy, the clinical cure rate on Day15 was 47.5% in SO-1105 group and 47.5% in Gel group, showing the similar efficacy between both groups. For safety, adverse drug reactions were observed in 29.0% of SO-1105 group and 24.6% of Gel group, showing the similar safety between both groups. Conclusion The efficacy of SO-1105 was shown to be similar to that of miconazole gel. Meanwhile, SO-1105 is an adhesive tablet and is administered once-daily. For this, SO-1105 is expected to better compliance and useful drug for the elderly. Therefore, SO-1105 is considered to be widely used in clinical practice as one of the therapeutic drugs for oropharyngeal candidiasis.

Summary Background and objective Forearm free flaps are used after hemiglossectomy. However, no investigation has been performed on whether oral functions are better preserved when sizes of the resection and reconstruction flap are exact matches, or whether the size of the resection should be changed. We aimed to retrospectively examine whether size differences between the resection and reconstruction flap affect speech and swallowing functions postoperatively, and to determine whether there are more favorable flap size ratios. Methods This is a retrospective cohort study of patients undergoing hemiglossectomy using a forearm free flap between 2006 and 2016 at Kobe University Hospital, Japan. The effect of size difference between the resection and reconstruction flap on maintained oral function was assessed. Speech and swallowing functions were assessed, and their correlation with the ratio of the flap size to that of the resected area was determined. With these data, distribution maps of the relationship between the functional level and reconstructed dimension ratio were prepared. The more suitable reconstructed dimension ratio was examined and evaluated. The Fisher exact test, Kruskal–Wallis test, and Scheffe test were used in statistical analyses. Results Eighty-eight patients underwent hemiglossectomy using a forearm free flap during a 10-year period. Of these cases, 66 patients were included in this study, while 22 were excluded. The ratio of the area of the reconstruction flap to that of the resection site was 0.59–2.79 (median: 1.61). Sixty patients had flaps greater than the resection area, whereas 6 had smaller flaps. Significant differences were found in speech intelligibility and swallowing function when the reconstructed dimension ratio was categorized as follows: ≤1.3, 1.3–1.8, and ≥1.8. Conclusion Our findings suggest that postoperative deterioration of oral functions after hemiglossectomy could be reduced if reconstruction is performed using a forearm free flap with a surface area 1.3 to 1.8 times greater than that of the resection area.

Background Postoperative pneumonia can be a fatal complication that may occur after lung resection in cancer patients. Some reports have shown that the incidence of postoperative pneumonia is decreased after esophageal surgery by perioperative oral care; however, there exist no data to suggest that a lack of perioperative oral care can be a risk factor for postoperative pneumonia after lung resection. To investigate the association between the preventive effect of oral care and postoperative pneumonia, we conducted a multicenter, retrospective study of lung cancer patients who underwent lung resection. Methods Between January 2014 and December 2016, a total of 721 patients underwent lung resections at 1 of the 6 hospitals included in our study. Among 721 patients, 280 (38.8%) received perioperative oral care, and the remaining 441 (61.2%) did not receive any such care. Propensity score matching was performed to minimize selection biases associated with the comparison of retrospective data between the oral care and control groups. Results Of the 721 patients, 54 (7.5%) experienced postoperative pneumonia involving 13 of the 280 patients (4.6%) in the oral care group and 41 of the 441 patients (9.3%) in the control group (P = .02). On propensity score analysis, a significant difference was also found between oral care intervention and incidence of postoperative pneumonia (P = .002). Conclusion Our results suggest that perioperative oral care is an effective method to decrease the occurrence of postoperative pneumonia in patients who have undergone lung resection.

Objective: The purpose of this study is to evaluate the efficacy of CO2 laser vaporization therapy for oral lichen planus (OLP) refractory to conservative treatments. Methods: The study gr...

Background This multicenter retrospective study aimed to determine whether elective neck dissection (END) can be performed for T1-2N0M0 tongue cancer. Methods Patients with T1-2N0M0 tongue squamous cell carcinoma who received treatment between January 2000 and December 2012 were enrolled at 14 multicenter study sites. The 5-year overall survival (OS) and 5-year disease-specific survival (DSS) were compared between the propensity score-matched END and observation (OBS) groups. Results The results showed that the OS rates among the 1234 enrolled patients were 85.5% in the END group and 90.2% in the OBS group (P = 0.182). The DSS rates were 87.0% in the END group and 94.3% in the OBS group (P = 0.003). Among the matched patients, the OS rates were 87.1% in the END group and 76.2% in the OBS group (P = 0.0051), and the respective DSS rates were 89.2% and 82.2% (P = 0.0335). Conclusion This study showed that END is beneficial for T1-2N0M0 tongue cancer. However, END should be performed for patients with a tumor depth of 4–5 mm or more, which is the depth associated with a high rate of lymph node metastasis. The use of END should be carefully considered for both elderly and young patients.

In brief, perioperative oral intervention consists of elimination of odontogenic foci and maintenance of oral hygiene in patients undergoing surgery. The importance of oral intervention before, during, and after medical treatments is well-known, especially in cancer patients, because odontogenic foci such as untreated deep dental caries or periodontitis can cause systemic infection in patients with myelosuppression resulting from chemotherapy. Although perioperative oral intervention is currently recommended for patients with cardiovascular disease, its efficacy in this population has not been established. This article consists of three sections: first, we review the current knowledge about the association between dental disease and cardiovascular disease to show the importance of oral hygiene maintenance and the risks of invasive dental procedures in patients with cardiovascular disease; second, we introduce pertinent, but limited evidence concerning the effect of oral care in preventing postoperative pneumonia; and finally, we present the optimal strategy for perioperative oral intervention in cardiovascular surgery patients.

Oroantral fistulas (OAF), which develop as a result of maxillary sinus infection caused by oroantral communication, are sometimes intractable. We present a case of closure with a facial artery musculomucosal flap (FAMM flap) for intractable OAF. A 73-year-old man presenting with an OAF and rhinorrhea was referred to our department. Twenty-eight years earlier, he had undergone bilateral radical surgery for maxillary sinusitis, and six years earlier, he underwent extraction of his right maxillary first and second molars. Six months after the dental extractions, he developed maxillary sinusitis secondary to oroantral communication. Four years after the dental extractions, he underwent endoscopic sinus surgery with closure of the OAF with a rotational pedicled palatal flap, but the OAF recurred. To treat the OAF recurrence, we used a FAMM flap. His postoperative course was good, with no OAF recurrence 6 years after surgery. FAMM flaps are useful to close intractable OAFs.

Summary Introduction Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, outcomes of these studies remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis. We investigated whether transcutaneous CO2 application can increase the survival of random-pattern skin flaps. Materials and methods Six-week-old male Sprague-Dawley rats were divided into two equal groups: the control group (n = 6) and CO2 group (n = 6). A random-pattern skin flap was constructed in these rats. Topical CO2 was applied using a hydrogel every day for 5 days in the CO2 group. The flap survival area was measured on postoperative days 1, 3, and 5. The vessel density and expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1α (HIF-1α) were evaluated on postoperative day 5. Results A statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p Conclusions Transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis, thus increasing the survival of random-pattern skin flaps.

Purpose The purpose of this study was to measure the frequency and identify factors associated with delayed socket healing after dental extraction in patients undergoing myelosuppressive chemotherapy for hematologic malignancy. Materials and Methods This prospective cohort study focused on delayed healing after extraction in patients with hematologic malignancy. Sockets with delayed healing were defined as those with intense pain and bone exposure 1 week postoperatively. Patients with and without delayed socket healing were compared using the Fisher exact test and Mann-Whitney U test with some variables. Receiver operating characteristics curve analysis was conducted to define cutoff values for delayed healing. Results One hundred ninety-four dental extractions in 93 patients (median age, 64 yr; range, 20 to 85 yr) were analyzed. The incidence of delayed socket healing was 7.5% (7 of 93 patients). There was no postoperative bleeding. Older age, type of hematologic malignancy (acute leukemia), shorter time from dental extraction to initiation of chemotherapy, low platelet count or hemoglobin level, requirement for red blood cell concentrate or platelet transfusion, and use of an absorbable hemostatic agent were statistically associated with the occurrence of delayed socket healing. Platelet and hemoglobin cutoffs were 4.6 × 104/μL and 7.7 g/dL, respectively. Conclusions Although dental extraction can be safely performed in patients undergoing myelosuppressive chemotherapy for hematologic malignancy, oral surgeons should understand the potential risk for delayed socket healing. When considering dental extraction, patients with hematologic malignancy and low hemoglobin or platelet levels should be informed about the possibility of delayed socket healing.

Objective Pain is one of the most problematic symptoms in patients with osteoradionecrosis of the jaws. This study investigated the associations between pain severity and morphologic alterations of the mandibular canal and inferior alveolar nerve, in respective computerized tomography images and resected specimens of mandibular osteoradionecrosis. Study Design We assessed 14 lesions in 13 patients who underwent segmental mandibulectomy for surgical debridement and simultaneous reconstruction with free fibula flap (1 patient exhibited bilateral lesions). The extent of the mandibular canal bone defect on preoperative coronal computerized tomography images and the number of inferior alveolar nerve fascicles in resected specimens were evaluated. Comparisons were made between the slight pain and extreme pain groups. In most of the patients in the extreme pain group, either mandibular canal bone defects were absent or entire circumferential defects were present; inferior alveolar nerve fascicles were either distinguishable or completely absent in the resected specimens. Results Although there was no statistically significant association between extreme pain and computerized tomography or histopathologic findings, the histopathologically indistinguishable inferior alveolar nerve fascicles was significantly associated with slight pain. Conclusions The degree of degeneration of mandibular canal and inferior alveolar nerve may be associated with pain severity in patients with mandibular osteoradionecrosis.

Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P

Purpose The reliability of dental implant treatments in oral cancer patients remains incompletely defined. The purpose of this study is to retrospectively investigate dental implants in oral cancer patients after jaw resection. Methods A total of 103 implants had been placed in 23 patients. We examined the clinical factors (gender, age, jaw location, implant position, bone augmentation, radiation therapy, chemotherapy, free flap reconstruction, osseous reconstruction) to predict the probability of implant removals. In addition, we examine about peri-implantitis and prosthetic systems. Results During the follow-up period, the 2 year survival rate was 91.3%, and the 5 year survival rate was 83.3%. We noted no serious adverse effects like malignant tumor recurrence or osteoradionecrosis from the implant site. Male patients, chemotherapy, and radiation therapy was identified to be significant risk factors associated with implant removals in the univariate analysis, and radiation therapy was identified to be a significant risk factor in the multivariate analysis. There were no significant differences between the each groups of prosthetic systems in implant removals. Free flap reconstruction was not demonstrated to be a significant risk factor for peri-implantitis. Conclusion The results of this study suggest that radiation therapy was associated with an increased risk of dental implant removals in oral cancer patients after jaw resection.

It was hypothesized that fluorodeoxyglucose (FDG) uptake on post-treatment follow-up positron emission tomography with computed tomography (PET CT; using PET CT to monitor and rule out recurrence and metastasis of head and neck carcinoma) would be useful for detecting and understanding the disease state of osteoradionecrosis (ORN) of the jaw. The present study included 14 patients who developed mandibular ORN following radiation therapy (RT) for head and neck cancer and underwent follow-up PET CT several times following RT. Areas exhibiting FDG uptake were retrospectively assessed on post-treatment follow-up PET CT images and were classified into three types: Spot type: Only spot accumulation of FDG; localized type: Accumulation of FDG restricted to within the bone resorption area; extensive type: Accumulation of FDG extending into surrounding soft tissue. PET classification at the time of clinical diagnosis of mandibular ORN in the 14 patients demonstrated the extensive type in 43%, localized type in 36% and spot type in 21%. An increased area of FDG uptake around the ORN was revealed retrospectively on post-treatment follow-up FDG PET-CT images in 50% of patients. Alterations in PET classification included spot type to localized type in 36% and localized type to extensive type in 14%. A significantly increased number of patients with extensive-type ORN (P=0.026) required surgery. Post-treatment follow-up FDG-PET CT may be useful for early detection and better understanding of ORN.

Objective: Dental injury is the most common complication of general anaesthesia. The primary purpose of this study was to report the occurrence, location, type, and treatment of dental injury caused by endotracheal intubation. Methods: This retrospective study evaluated 36,627 cases of general anaesthesia at our hospital from January 2008 through December 2015. The examination items included risk factors such as age; sex; surgical department; type of intubation(orotracheal or nasotracheal intubation); presence of preoperative trismus; Cormack–Lehane classification; experience of the attending anaesthesiologist; intubation appliance; mouth guard use; tooth mobility diagnosed by attending anaesthesiologist before surgery; the location, type, and treatment of injured teeth; and forensic implications. Results: The incidence of dental injury was 0.06% (22 of 36,627 patients). There was a significant difference in the rate of dental injury according to age (0.026% among those

The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

Background: The lack of uniformity of criteria for defining recipient-site infection after oral oncologic surgery with simultaneous reconstruction is problematic despite numerous studies on this issue. This study aimed to investigate the difference in the criteria for defining recipient-site infection after oral oncologic surgery with reconstruction. Methods: A Medline search was performed via PUBMED using the following combinations of key terms that were tagged in the title, abstract, or both: "surgical site infection-head neck," "surgical site infection-oral cancer," "antibiotic prophylaxis-head neck," and "surgical site infection-oral carcinoma." Search results were filtered between 2005 and 2017. Articles in which there was no mention of the criteria for definition of surgical-site infection were excluded. Results: The number of articles that met the inclusion criteria was 24. The lack of uniformity in the criteria for defining recipient-site infection in each article appeared to be attributable mainly to differences in whether an orocutaneous fistula and superficial incisional infection were regarded as recipient-site infection. Conclusion: Reconsideration of the categorization of orocutaneous fistula as infection, regardless of the etiology, and differentiation of superficial and deep incisional infections are necessary for correct assessment of recipient-site infection in oral oncologic surgery.

Objective: The purpose of this study was to retrospectively evaluate the postoperative results of partial glossectomy for early tongue cancer using a carbon dioxide laser (CO2 laser). Background data: CO2 lasers are frequently used for the excision or treatment of soft tissue in a range of diseases, including oral cancer, leukoplakia, mucocele, anomalies of the labial and lingual frenum, and peri-implantitis. Materials and methods: We retrospectively reviewed 31 primary cases of early superficial tongue cancer that were treated using CO2 lasers. In this study, early superficial cancer of the tongue is defined as a T1 or T2 tumor (TNM classification, NOMO; type, superficial spread, or exophytic; depth

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event that may inhibit the treatment of primary disease and remarkably influence the patient's quality of life. The treatment methods for MRONJ, nonsurgical and surgical, are controversial, with no agreement as to which method provides the best outcome and should therefore be recommended. This multicenter retrospective study aimed to investigate the treatment methods and outcome in a large number of patients with MRONJ in Japan, utilizing propensity score matching analysis. A total of 361 patients with MRONJ, at eight hospitals, were registered in this study retrospectively. Various demographic and treatment-related variables were examined and analyzed to determine their correlation with the treatment outcome. After propensity score matching for treatment methods (nonsurgical versus surgical treatment), 176 patients were analyzed by logistic regression. It was shown that those with low-dose administration of an antiresorptive agent and surgical treatment had better outcomes. Furthermore, in 159 patients who underwent surgical treatment, those who underwent extensive surgery experienced significantly better treatment outcomes than those who underwent conservative surgery. This is the first study to compare treatment methods for MRONJ using propensity score matching analysis. The results indicated that extensive surgical treatment should be performed as first-choice therapy for patients with MRONJ. © 2017 American Society for Bone and Mineral Research.

Resection of buccal mucosa tumors may occasionally involve the labial angle and peripheral skin. Reconstruction is required when the resection involves more than one-third of the lip. We describe a single-stage reconstruction using a facial artery musculomucosal (FAMM) flap and a vermilion advancement flap after buccal mucosa resection including the labial angle. A 62-year-old woman with carcinoma in situ of the buccal mucosa underwent tumor resection. The resection included the right labial angle and peripheral skin. The resection did not lead to a massive lip defect, but a wide defect resulted on the mucosal side. The defect on the mucosal side was reconstructed using a FAMM flap, while the vermilion defect was covered using a vermilion advancement flap. Reconstruction performed using the FAMM flap and vermilion advancement flap produced aesthetically and functionally satisfactory outcomes.

Objective Previous reports regarding postoperative drainage have documented complications associated with the drainage volume (DV). However, there is little information available concerning the postoperative and operative factors that influence postoperative DV. In this study, we retrospectively investigated the relationship between postoperative drainage and various risk factors in patients undergoing head and neck surgery for oral cancer. Methods This study included 136 patients (88 males, 48 females, mean age 67.2 ± 12.9 years) who underwent head and neck surgery for oral cancer. We retrospectively investigated the following variables: age, sex, subsite, medical history, surgical procedure, operative time, blood loss, duration of drain retention, DV, and postoperative complications. Results DV after reconstruction with a pectoral major musculocutaneous flap was significantly higher than DV after reconstruction with a forearm flap ( p p p p Conclusions DV was greater in those with older age, antithrombotic therapy, advanced surgery, and wide-ranging neck dissection. Therefore, clinicians should consider these risk factors and pay special attention to the postoperative management of drains in such cases.

Root amputation, extraction of a single tooth, bone loss or severe tooth mobility, and an unclosed wound were significantly associated with increased risk of developing medication-related osteonecrosis of the jaw (MRONJ). We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. Osteonecrosis of the jaws can occur following tooth extraction in patients receiving bisphosphonate drugs. Various strategies for minimizing the risk of MRONJ have been advanced, but no studies have comprehensively analyzed the efficacy of factors such as primary wound closure, demographics, and drug holidays in reducing its incidence. The purpose of this study was to retrospectively investigate the relationships between these various risk factors after tooth extraction in patients receiving oral bisphosphonate therapy. Risk factors for MRONJ after tooth extraction were evaluated using univariate and multivariate analysis. All patients were investigated with regard to demographics; type and duration of oral bisphosphonate use; whether they underwent a discontinuation of oral bisphosphonates before tooth extraction (drug holiday), and the duration of such discontinuation; and whether any additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. We found that root amputation (OR = 6.64), extraction of a single tooth (OR = 3.70), bone loss or severe tooth mobility (OR = 3.60), and an unclosed wound (OR = 2.51) were significantly associated with increased risk of developing MRONJ. We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. We find no evidence supporting the efficacy of a pre-extraction short-term drug holiday from oral bisphosphonates in reducing the risk of MRONJ.

Odontogenic foci can rarely cause intracranial infection. Hematogenous spread is considered to be the most important pathophysiological mechanism of intracranial infection of odontogenic origin. To investigate the oral origin of intracranial infections, oral surgeons should understand the underlying mechanisms by which oral bacteria spread to the central nervous system. However, there have been very few reports of intracranial infection resulting from odontogenic infection. The authors report the cases of a 64-year-old man, a 68-year-old man, and a 64-year-old woman whose brain abscesses perhaps have arisen from odontogenic foci, because other sources of intracranial infection such as endocarditis and maxillary sinusitis were not found. Bacteriological examination of brain abscess specimens identified Staphylococcus aureus in case 1, Streptococcus constellatus, Fusobacterium nucleatum, and Parvimonas micra in case 2, and Lactobacillus catenaformis, Porphyromonas gingivalis, and Fusobacterium nucleatum in case 3. All suspected causal teeth had no obvious signs of acute inflammation in 3 cases. Oral surgeons should understand these characteristics of odontogenic brain abscess, in which the potentially causal odontogenic foci often lack acute symptoms. If other origins of infection are not found, it would be better to eliminate the potentially causal odontogenic foci for improvement of oral hygiene, however, the decision making criteria to eliminate suspected causal teeth is needed to be elucidated.

Aim To suggest regarding the timing of oral surgery and laser treatment for frenulum abnormalities in the pediatric population. Materials and methods We investigated the sex, age, frenulum site, reason for consultation, treatment method, and prognosis of 35 patients aged 15 years or younger and who were examined at our hospital for the chief complaint of frenulum abnormality. Results A total of 21 (mean age, 6.0 years) of the 35 patients underwent frenectomy using a carbon dioxide (CO2) laser. Of these, 7 patients (mean age, 2.8 years) underwent the procedure with general anesthesia and 14 patients (mean age, 7.6 years) underwent the procedure with local anesthesia. The surgical site was the lingual frenulum in 15 patients and the maxillary labial frenulum in 6 patients. No adverse events were intraoperatively reported in any of the patients, and the procedure was quickly and safely performed. The mean postoperative follow-up period was 4.6 months, and readhesion was noted in one patient (4.8%). The most common reason cited for not undergoing frenectomy in the 14 patients (mean age, 3.4 years) was the young age of the child. Conclusion Retrospective study of pediatric patients with frenulum abnormalities demonstrated the usefulness of the CO2 laser in performing frenectomy and offered suggestions regarding the timing of this procedure. Clinical significance Frenectomy performed using a CO2 laser for pediatric patients is a useful, simple, and safe treatment method. How to cite this article Komori S, Matsumoto K, Matsuo K, Suzuki H, Komori T. Clinical Study of Laser Treatment for Frenectomy of Pediatric Patients. Int J Clin Pediatr Dent 2017;10(3):272-277.

The submandibular gland (SMG) is one of the major salivary glands that play important roles for variety of physiological functions, such as digestion of foods, prevention of infection, and lubrication of the mouth. Dysfunction of the SMG, often associated with a salivary inflammation, adversely influences a person's quality of life. However, the mechanism underlying inflammation-driven dysfunction of the SMG is largely unknown. Here, we used a mouse model in which the main excretory duct of the SMG is ligated unilaterally to induce inflammation of the gland and examined the expression of Wnt5a, Ror1 and Ror2 genes, encoding Wnt5a ligand and its cognate receptors, which have been implicated in tissue damage or inflammatory responses in variety of tissues. We show that expression levels of Ror1, Ror2, and Wnt5a are increased in the ligated SMG undergoing interstitial fibrosis, which is accompanied by robust expression of fibrosis-associated genes, such as TGF-β1, TNF-α, IL-1β, and MMP-2. Increased immunostaining signal of Ror2 was detected in the fibrotic tissues with abundant accumulation of fibroblasts and collagen fibers in the ligated SMG, suggesting that Ror2-mediated signaling might be activated in response to tissue damage and associated with progression of fibrosis in the SMG.Key words: submandibular gland, Ror2, Wnt5a, fibrosis, inflammation.

Objective: This retrospective study aimed to report the incidence of neurosensory complications after third molar extraction and also to identify current problems and discuss appropriate management of these complications. Method: Patients who underwent extraction of deeply impacted mandibular third molars under general anesthesia were included. The following epidemiological data were retrospectively gathered from medical charts: type of neurosensory complication, treatment for complication, and outcome. Results: A total 369 mandibular third molars were extracted in 210 patients under general anesthesia during this study period. Thirty-one of the 369 teeth (8.4%) in 31 patients had neurosensory complications during the first postoperative week resulting from inferior alveolar nerve damage. Neurosensory complications lasting from 1 to 3 months postoperatively included 17 cases of hypoesthesia and 8 of dysesthesia in 19 patients. Five cases of hypoesthesia and 4 of dysesthesia in 5 patients persisted over 1 year postoperatively. Sixteen of 369 teeth (4.3%) in 16 patients had persistent neurosensory complications after third molar extraction under general anesthesia. Stellate ganglion block was performed in 4 patients. Early initiation of stellate ganglion block (within 2 weeks postoperatively) produced better outcomes than late stellate ganglion block (over 6 months postoperatively). Conclusion: Refractory neurosensory complications after third molar extraction often combine both hypoesthesia and dysesthesia. Current problems in diagnosis and treatment included delayed detection of dysesthesia and the lack of uniform timing of stellate ganglion block. In the future, routinely inquiring about dysesthesia and promptly providing affected patients with information about stellate ganglion block might produce better outcomes.

The present retrospective multicenter study intended to investigate the factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas. A total of 326 patients who underwent radiotherapy for oral and oropharyngeal cancers were enrolled in the study. The patients’ age, sex, body mass index, primary site, diabetes, serum albumin, creatinine, hemoglobin, leukocyte and lymphocyte, concurrent cisplatin or cetuximab, method of radiation, total radiation dose, feeding route, use of spacers, pilocarpine hydrochloride, and corticosteroid ointment were examined, and the associations of each variable with oral mucositis and candidiasis were analyzed by multivariate Cox regression analysis. Grade 3 oral mucositis occurred in 136 (41.7%) patients. Male sex, oropharyngeal cancer, low hemoglobin levels, low leukocytes or lymphocytes, concurrent cisplatin or cetuximab, and oral feeding were found to be significantly associated with a higher incidence of severe oral mucositis. Oral candidiasis occurred in 101 (31.0%) patients. Oropharyngeal cancer, low leukocyte count, and oral mucositis of grade 2 or higher were found to be significantly associated with a higher incidence of oral candidiasis. The use of a topical steroid ointment was not found to be a risk factor for oral candidiasis. The present retrospective study demonstrated that certain factors may predispose patients with oral and oropharyngeal cancers receiving radiotherapy to develop severe oral mucositis and oral candidiasis. A preventive strategy for severe oral mucositis needs to be established in the future for high-risk cases.

Treatment strategies of medication-related osteonecrosis of the jaw (MRONJ) are controversial. Recently, surgical treatment has been reported as superior to nonsurgical treatment, but the contribution discontinued antiresorptive agent use during MRONJ treatment remains unclear. This study aimed to evaluate the efficacy of drug holidays and treatment strategies in MRONJ cases. Four-hundred and twenty-seven patients with MRONJ treated at nine hospitals from 2009 to 2017 were included in this multicenter retrospective study. Multivariate Cox regression analysis showed that the primary disease (osteoporosis or malignant tumor), diabetes, serum albumin, and treatment method (surgical or nonsurgical) were significantly correlated with the cure rate. The cumulative 1-year cure rates in the surgical and nonsurgical treatment groups were 64.7% and 18.2%, respectively. However, discontinuing antiresorptive agents did not influence the treatment outcome in the cohort overall, or in 230 patients after performing propensity score matching among the discontinuation and continuation groups. When stratifying by treatment method, antiresorptive agent discontinuation significantly increased the cure rate in patients with osteoporosis who underwent nonsurgical treatment. In patients with malignant tumors undergoing nonsurgical therapy, discontinuing the antiresorptive agent was associated with a better treatment outcome, but not with statistical significance. In contrast, drug holidays showed no effect on improving outcomes in patients with both osteoporosis and malignant tumors who underwent surgical therapy. Thus, regardless of the primary disease, discontinuing antiresorptive agents during treatment for MRONJ may not be necessary and may be helpful in some cases. Future prospective trials should examine this question further.

Background/aim We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis. Materials and methods iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated. Results No evidence of statistically significant relationships was found between the expression of iPS cell-related genes and clinicopathological parameters. However, our data indicated that KLF4 expression was associated with survival, and poor tumor differentiation. In addition, high expression of KLF4 was an independent poor prognostic factor (p=0.004) for OSCC patients. Conclusion In preoperative biopsies, higher KLF4 and poor differentiation may be clinically effective predictors for the prognosis of oral cancer.

OBJECTIVE The authors investigated the clinical and histopathologic significance of medial pectoral nerve preservation/reinnervation of pectoralis major musculocutaneous flap for oromandibular reconstruction. MATERIALS AND METHODS The authors compared 13 patients treated with pectoralis major musculocutaneous flap reconstruction and 6 control patients treated by rectus abdominis musculocutaneous flap reconstruction without motor nerve restoration. Subjective awareness was scored to evaluate changes in the facial contour due to muscle atrophy, and objective evaluation was performed in few patients. In addition, the authors performed histopathologic analysis of both muscle atrophy and nerve regeneration in 20 patients from whom samples were available. RESULTS Subjective awareness of changes in the facial contour induced by muscle atrophy was low among patients with nerve preservation/reinnervation, but there were objective changes at 3 months after surgery among patients who underwent nerve resection. In the patients who had medial pectoral nerve preservation or nerve restoration by nerve suture, favorable facial symmetry was retained at 5 years after surgery. Even though the motor nerve was preserved or restored, fatty degeneration and fibrosis were noted in approximately 30% of the total surface area of the muscle, and type I fibers had decreased to 36% that of control at 7 years after surgery. However, regressive changes were inhibited for 1 year after surgery; in contrast, changes corresponding to those noted at 7 years after surgery were observed by 3 months in the patients with nerve resection. CONCLUSION Thus, the authors showed that preservation or restoration of nerves can delay muscle and have highlighted the potential benefits of this approach.

A multi‐institutional study was undertaken to determine whether mandibular canal (MC) invasion and mandibular medullary bone invasion are independent factors in lower gingival squamous cell carcinoma (SCC). A total of 345 patients with lower gingival SCC were retrospectively reviewed. Mandibular bone invasion was categorized into three types; no bone invasion; invasion through cortical bone (medullary); and MC invasion. The overall survival rate and factors affecting local, regional, and distant failures were assessed by Cox proportional hazards regression analysis and Kaplan–Meier estimates. Bone invasion was present in 201 (58%) patients, of whom 107 (31%) had medullary invasion and 94 (27%) had MC invasion. Using the International Union Against Cancer (UICC) staging system and American Joint Committee on Cancer (AJCC) system, 171 (50%) patients were classified as T4a. When the bone invasion criteria were excluded from the UICC/AJCC system definition, 152 T4a tumors were downstaged and reclassified to T1 in 12 (3%), to T2 in 98 (28%), and to T3 in 42 (12%). In Cox multivariate analysis, MC invasion was an independent predictor of overall survival but medullary bone invasion was not. Medullary bone invasion was an independent variable for distant control. The current T staging system has restricted prognostic utility. The authors recommend a modified T staging system, whereby tumors with MC invasion instead of medullary bone invasion are classified as T4a, and tumors are first classified as T1 to T3 based on size and then upstaged by one T classification in the presence of medullary invasion.

Objective In this study, we investigated the degree of concordance in the histopathological diagnosis among lesions clinically diagnosed with oral lichen planus (OLP) to understand the importance of the histopathological examination. Methods In total, 169 patients clinically diagnosed with OLP on their initial visit to our hospital between 2001 and 2012 were experienced. Of them, histopathological examinations were carried out for 77 patients (83 lesions), and they were selected as the subjects of this study. The age, gender, location of the lesion, clinical type of OLP determined via visual inspection, and histopathological findings were investigated. Results Of the 77 patients, 12 were male and 65 were female, with a mean age of 63.9 years. Histopathological examinations were performed in 83 lesions, of which 54 were diagnosed as OLP. Among the diagnostically discordant 29 lesions, most were histopathologically diagnosed as leukoplakia (15 lesions, 51.7%), whereas one was diagnosed as squamous cell carcinoma (3.4%). The most frequent location of discordant lesions was the tongue (discordant rate: 77.8%), and the most clinical type was plaque (discordant rate: 90.0%); all of which were atypical types of OLP. Conclusions The rate of discordance between the clinical and histopathological diagnoses was 34.9%. These results indicate that histopathological examinations are essential for obtaining the differential diagnosis to distinguish the lesion from other diseases with a clinical presentation similar to that of OLP.

Oral squamous cell carcinoma (OSCC) is the most common form of oral cancers. Recent studies have shown that the malignant transformation of various carcinomas, including OSCC, is associated with epithelial-mesenchymal transition (EMT), and that expression of the EMT factors are significantly associated with tumor invasion, tumor metastasis, and survival rates in OSCC patients. Hence, there is a possibility that EMT suppression may improve the prognosis of OSCC patients. Hypoxia inducible factor-1α (HIF-1α) is a crucial microenvironmental factor in tumor progression, which induces the expression of EMT factors. We previously reported that transcutaneous CO2 suppresses both human OSCC tumor growth and metastasis to the regional lymph nodes by improving hypoxia in treated tissue. According to this background, we hypothesized that increased EMT with HIF-1α expression may increase the progression and the metastatic potential of OSCC, and that decreased hypoxia by transcutaneous CO2 could suppress EMT. In the present study, in vitro studies showed that hypoxic conditions increased the expression of HIF-1α and EMT factors in OSCC cells. In addition, in vivo studies revealed that transcutaneous CO2 increased E-cadherin expression with the decreased expression of HIF-1α, Snail, Slug, N-cadherin, and Vimentin in tumor treatment. These results suggest that transcutaneous CO2 could suppress EMT by improving hypoxia, resulting in the reduction of metastatic potential of OSCC. The findings indicate that transcutaneous CO2 may be able to improve the prognosis of OSCC patients through the suppression of EMT.

Objective This study aimed to compare postoperative outcomes between free-flap reconstruction and prosthesis after secondary healing for moderate-sized maxillectomy defects. Methods We enrolled patients who underwent tumor ablation extending to the alveolus, antral walls, masticatory space, and surrounding soft tissue but not the orbital floor with either radial forearm free-flap reconstruction (RFFF) or no reconstruction (NR) and compared the extent of cheek concavity on the resected side, evaluated using axial computed tomography images, and time to prosthesis insertion between the RFFF and NR groups. Results There was a significant difference between the RFFF and NR groups in operative duration (P = 0.010) but not blood loss. The postoperative cheek concavity was significantly smaller in the RFFF group (P = 0.037). Although the between group difference in time to prosthesis insertion was not significant, prostheses tended to be inserted earlier in the RFFF group; median time to prosthesis insertion was 49 days in the RFFF group and 67 days in the NR group. Conclusions Reconstruction of a moderate-sized maxillectomy defect with radial forearm free-flap transfer can improve postoperative outcome.

Only a few reports on the level of progression of extracapsular spread (ECS) have been published. The aim of this study was to evaluate the efficacy of the level of progression of ECS in identifying those patients with oral squamous cell carcinoma (OSCC) at a high risk of recurrence who would benefit most from the intensification of adjuvant therapy. The level of progression of ECS for cervical lymph node metastasis in OSCC was divided into three types (A-C), and their relationships with patient prognosis were examined. ECS was observed in 87 of 441 patients with OSCC. The recurrence rate in patients with type C, which was defined as macroscopic tumour invasion into perinodal fat or muscle tissue, was high (69.8%), with 13 cases of death due to distant metastasis. The 3-year disease-specific survival rate for patients with type C was 49.0% and these patients also had a significantly poorer prognosis (P

Purpose Patients with oral cancer who undergo resection with simultaneous reconstruction are presumed to be at high risk for developing venous thromboembolism (VTE) according to current criteria. The primary purpose of this retrospective study was to report the incidence of VTE after oral cancer surgery requiring primary reconstruction and to identify the potential risk factors for VTE in this population. Materials and Methods This retrospective study evaluated 133 consecutive patients who had undergone oral cancer resection with simultaneous reconstruction from April 2007 through December 2014. Bilateral lower-extremity venous duplex ultrasonography (VDUS) was routinely performed 2 days after surgery. Pulmonary embolism was confirmed with computed tomography. The Caprini risk score (CRS) was obtained for each patient. Patients with and without VTE were compared using the χ 2 test and Student t test with some variables. Univariate predictors associated with VTE were entered into a multivariate logistic regression analysis. A P value less than .05 was regarded as indicating statistical significance. Results The incidence of VTE after oral oncologic surgery with simultaneous reconstruction was 26.3% (35 of 133 patients): deep vein thrombosis (DVT) and pulmonary embolism occurred in 2.3% (3 of 133) and DVT alone was found in 24.0% (32 of 133). Multivariate logistic regression analysis showed that only a high CRS was statistically relevant to VTE occurrence. Conclusions Because a high incidence of VTE was found after major oral and maxillofacial surgery, lower-extremity VDUS should be undertaken in patients who undergo oral cancer surgery with simultaneous reconstruction, especially those with a high CRS.