OPN4 belongs to the photosensitive system of the human skin.

The human skin has previously been described to be affected by light; however, the underlying mechanism remains unknown. OPN4 (melanopsin) expression was first identified in the skin of amphibians; however, whether it is also expressed and functioned in the human skin has not yet been identified. Here, we show that OPN4 was expressed in the human skin tissue and cultures of isolated keratinocytes, melanocytes and fibroblasts. Additionally, Ca2+ influx in vitro and ex vivo and phosphorylation of extracellular signal-regulated kinases 1/2 in human fibroblasts were observed by stimulation of blue light irradiation. Notably, our findings showed that this Ca2+ influx and phosphorylation of extracellular signal-regulated kinases 1/2 are promoted in an intensity-dependent manner, indicating that the light signal is converted to an intracellular signal via OPN4 in the human skin. Overall, in this study we showed that the human skin functions as a photoreceptor by demonstrating that in human skin, the photoreceptive protein was expressed, and photoreception was conducted via photoreceptive protein.

Drug holiday clinical relevance verification for antiresorptive agents in medication-related osteonecrosis cases of the jaw.

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.

Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

A Multicenter Retrospective Study of Elective Neck Dissection for T1-2N0M0 Tongue Squamous Cell Carcinoma: Analysis Using Propensity Score-Matching.

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.

Tumor budding and adjacent tissue at the invasive front correlate with delayed neck metastasis in clinical early-stage tongue squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Some patients with early-stage oral cancer have a poor prognosis owing to the delayed neck metastasis (DNM). Tumor budding is reportedly a promising prognostic marker in many cancers. Moreover, the tissue surrounding a tumor is also considered to play a prognostic role. In this study, we evaluated whether tumor budding and adjacent tissue at the invasive front can be potential novel predictors of DNM in early tongue cancer. METHODS: In total, 337 patients with early-stage tongue squamous cell carcinoma were retrospectively reviewed. The patient characteristics and histopathological factors were evaluated for association with DNM. DNM rates were calculated; items which were significant in the univariate analysis were used as explanatory variables, and independent factors for DNM were identified by the multivariate analysis. RESULTS: The univariate analysis identified T classification, depth of invasion, tumor budding, vascular invasion, and adjacent tissue at the invasive front as significant predictors of DNM; the multivariate analysis using these factors revealed all the above variables except vascular invasion, which are independent predictors of DNM. CONCLUSION: In addition to conventional predictors, high grade tumor budding and adjacent tissue at the invasive front can serve as useful predictors of DNM in early tongue cancer.

Long-Term Effects on Volume Change in Musculocutaneous Flaps after Head and Neck Reconstruction.

OBJECTIVE: Musculocutaneous flap reconstruction surgery is one of the standard procedures following head and neck cancer resection. However, no previous studies have classified flaps in terms of muscle and fat or examined them after long-term follow-up. The purpose of this study was to estimate the fat and muscle volume changes in musculocutaneous flaps during long-term follow-up. METHODS: We conducted a retrospective analysis of 35 patients after musculocutaneous flap reconstruction. The total, fat, and muscle volumes of the musculocutaneous flaps were measured using 3-dimensional images. Changes in flap volumes over time (1 month, 1 year [POY1], and 5 years [POY5] postoperatively) were assessed. Flap persistence was calculated using flap volumes at 1 month after reconstruction for reference. RESULTS: Flap persistence at POY5 was 42.0% in total, 64.1% in fat, and 25.4% in muscle. Muscle persistence was significantly decreased (p < 0.0001). In a multiple regression analysis, decreased body mass index (BMI) of ≥ 5% influenced fat persistence less than muscle persistence at POY1; however, there was no significant difference at POY5. Postoperative radiation therapy was associated with a significant decrease in total flap persistence at POY1 (p = 0.046) and POY5 (p = 0.0097). Muscle persistence significantly decreased at POY5 (p = 0.0108). Age significantly influenced muscle volume at POY1 (p = 0.0072). CONCLUSION: Reconstruction flaps are well-preserved with high fat-to-muscle ratios. Recommendations for weight maintenance are necessary for patients less than 2 years after surgery due to the influence of BMI on fat persistence. Radiation therapy is necessary for some patients based on their disease state. Intensity-modulated radiation therapy can be offered to reduce scattering irradiation to normal tissues.

Multi-center retrospective study of the prognosis and treatment outcomes of Japanese oral squamous cell carcinoma patients with single lymph node metastasis and extra nodal extension.

BACKGROUND: Oral squamous cell carcinoma (OSCC) containing single lymph node metastasis (pN1) with extra nodal extension (ENE) is a rare clinical situation. Therefore, it is unclear whether pN1 with ENE is at high risk of recurrence among the OSCC population, or whether postoperative radiotherapy (RT)/concomitant chemoradiotherapy (CCRT) is effective in these cases. OBJECTIVES: The purpose of this retrospective study was to investigate the prognosis and compare between no postoperative therapy and postoperative RT/CCRT in pN1 with ENE OSCC patients. METHODS: Clinicopathological data and treatment modalities were investigated. The evaluated endpoints were overall survival (OS) and type of recurrence. RESULTS: The 3-year cumulative OS rates for the pN1 only, multiple lymph node metastasis (MLM) only, ENE + MLM, and ENE + pN1 groups were 77.2%, 66.8%, 43.3%, and 66.6%, respectively. In the ENE + pN1 group, the most common cause of death in the surgery only group was from regional failure. The surgery + RT/CCRT group was associated with better disease-specific survival and OS rates than the surgery only groups (P < 0.05). CONCLUSIONS: The prognosis of ENE + pN1 was not as poor as that of ENE + MLM, although both these groups feature ENE. Adjuvant therapy (RT/CCRT) after surgery is recommend for cases of ENE + pN1.

Four-Dimensional Computed Tomography Evaluation of Condylar Movement in a Patient With Temporomandibular Joint Osteoarthritis.

Temporomandibular joint (TMJ) osteoarthritis (OA) is a disease of the bone, cartilage, and supporting tissues of the joint. Patients with advanced TMJ-OA often have symptoms such as pain, swelling, and joint dysfunction, and they sometimes require surgical intervention when conservative treatment is not effective. The etiology of TMJ-OA remains elusive. The usefulness of 4-dimensional (4D) computed tomography (CT) in motion analysis of various joints has recently been reported. This article introduces a novel imaging technique of 4D CT that aims to identify kinematic features that may be associated with the etiology of TMJ-OA. In a 69-year-old female patient with severe TMJ-OA, 4D CT evaluation of condylar movement was performed. During the scan, she was instructed to masticate a cookie normally and her natural condylar movement during mastication was evaluated. The coronal 4D CT motion images showed that the synovial cavity was narrower on the affected side than on the unaffected side. Repeated friction between the articular surface of the condyle and the caudal surface of the articular eminence was observed during natural mastication. Although friction between the condyle and articular eminence has been considered a factor in the initiation and progression of TMJ-OA in previous experimental studies using animals, this is the first study to directly visualize the friction between the atrophic and flattened condylar surface and the articular eminence. Four-dimensional CT is a novel imaging technique with the potential to assess kinematic features that cannot be visualized with other imaging modalities in patients with TMJ disease.

Delayed Socket Healing After Dental Extraction in Patients Undergoing Myelosuppressive Chemotherapy for Hematological Malignancy: Incidence and Risk Factors.

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.

Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. CLINICAL RELEVANCE: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

Expression of Ror2 Associated with Fibrosis of the Submandibular Gland.

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-ß1, TNF-α, IL-1ß, 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.

A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development.

Mammary gland development is induced by the actions of various hormones to form a structure consisting of collecting ducts and milk-secreting alveoli, which comprise two types of epithelial cells known as luminal and basal cells. These cells adhere to each other by cell adhesion apparatuses whose roles in hormone-dependent mammary gland development remain largely unknown. Here we identified a novel cell adhesion apparatus at the boundary between the luminal and basal cells in addition to desmosomes. This apparatus was formed by the trans-interaction between the cell adhesion molecules nectin-4 and nectin-1, which were expressed in the luminal and basal cells, respectively. Nectin-4 of this apparatus further cis-interacted with the prolactin receptor in the luminal cells to enhance the prolactin-induced prolactin receptor signaling for alveolar development with lactogenic differentiation. Thus, a novel nectin-mediated cell adhesion apparatus regulates the prolactin receptor signaling for mammary gland development.

Multicenter Retrospective Study of the Risk Factors of Hemorrhage After Tooth Extraction in Patients Receiving Antiplatelet Therapy.

PURPOSE: To identify the risk factors affecting hemorrhage after tooth extraction in patients receiving antiplatelet therapy, this study investigated the relation between various factors and hemorrhage events after tooth extraction. PATIENTS AND METHODS: The records of 264 patients receiving antiplatelet therapy who underwent tooth extraction were retrospectively reviewed from 6 institutions belonging to the Japanese Study Group of Cooperative Dentistry with Medicine. Demographic information, hemorrhage events after tooth extraction, the presence or absence of comorbidities, antiplatelet agent, the use of preoperative antibiotics or nonsteroidal anti-inflammatory drugs, number of teeth extracted, serum creatinine level, estimated glomerular filtration rate, and alanine transaminase level were assessed. Risk factors for hemorrhage after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: The study population of 264 patients consisted of 153 men and 111 women with a mean age of 73.6 years (range, 24 to 96 yr). Six hundred ninety-four teeth were extracted (mean, 2.6 ± 2.3 teeth per patient). In patients receiving antiplatelet therapy, the frequency of hemorrhage after tooth extraction, including mild and self-controlled hemorrhages, was 17.4%. Univariate analysis showed that serum creatinine level and dual antiplatelet therapy were correlated with hemorrhage after tooth extraction (P = .001 and P = .049, respectively). Only serum creatinine was identified as an independent risk factor for hemorrhage after tooth extraction in patients receiving antiplatelet therapy (P = .037). CONCLUSIONS: The risk of hemorrhage after tooth extraction is increased in patients receiving dual antiplatelet therapy with or without chronic kidney disease. Local hemostatic treatments, such as at least suturing, are recommended.

The maximum standardized uptake value increment calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography predicts survival in patients with oral tongue squamous cell carcinoma.

The aim of this study was to investigate the prognostic value of dual-time-point (DTP) 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging in primary oral tongue squamous cell carcinoma (OTSCC). The study included 52 patients who underwent preoperative 18F-FDG PET scans at two time points, namely 1 h and 2 h after injection. The following PET parameters were calculated: maximum standardized uptake value (SUVmax) for both time points (SUV early, SUV delayed); retention index (RI); and SUVmax increment (ΔSUVmax). Receiver operating characteristic (ROC) curve analysis was performed to define the optimal cutoff point for these parameters. Overall survival was calculated using the Kaplan-Meier method. Prognostic factors for patients with OTSCC were evaluated using the univariate log-rank test and a multivariate Cox proportional hazards model. ROC analysis revealed that the area under the curve was higher and more accurate for ΔSUVmax than for the other parameters. Additionally, patients with a ΔSUVmax ≥0.9 had significantly worse survival outcomes (28.9% vs 92.6%; p < 0.01). Univariate analysis showed that prognosis was significantly correlated with clinical T stage, local recurrence, perineural invasion, vascular invasion, and PET parameters (p < 0.05 for all). Multivariate analysis showed that local recurrence (hazard ratio = 3.60; p = 0.02) and ΔSUVmax (hazard ratio = 8.43; p < 0.01) were independent prognostic factors. ΔSUVmax determined using DTP 18F-FDG PET may be an additional prognostic factor in OTSCC patients.

Magnitude of Myocutaneous Flaps and Factors Associated With Loss of Volume in Oral Cancer Reconstructive Surgery.

PURPOSE: Myocutaneous flaps are often used to repair oral and maxillofacial defects after surgery for oral cancer; however, their volume decreases during the postoperative period. To facilitate treatment planning, the authors measured the extent of such postoperative flap volume loss and identified associated factors in patients who underwent oral reconstruction with myocutaneous flaps. MATERIALS AND METHODS: The authors designed and performed a retrospective observational study of patients who underwent reconstructive procedures involving rectus abdominal myocutaneous (RAM) or pectoralis major myocutaneous (PMMC) flaps at Tokai University Hospital, Kobe University Hospital, or Nagasaki University Hospital from April 2009 through March 2013. Flap type and other clinical variables were examined as potential predictors of flap loss. The primary outcome was flap loss at 6 months postoperatively. Correlations between each potential predictor and the primary outcome were examined using multiple regression analysis. RESULTS: The subjects were 75 patients whose oral defects were reconstructed with RAM flaps (n = 57) or PMMC flaps (n = 18). RAM flaps exhibited a mean volume shrinkage of 22% at 6 months postoperatively, which was less than the 27.5% displayed by the PMMC flaps, but the difference was not important. Renal failure, previous surgery of the oral region, postoperative radiotherapy, and postoperative serum albumin level were found to be meaningful risk factors for postoperative flap volume loss. CONCLUSION: The results of this study suggest that larger flaps should be used in patients who possess these risk factors or are scheduled to undergo postoperative radiotherapy. Future studies should examine the utility of postoperative nutritional management for preventing flap volume loss.

Incidence of Venous Thromboembolism After Oral Oncologic Surgery With Simultaneous Reconstruction.

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 χ2 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.

Motor Nerve Preservation and Muscle Atrophy After Pectoralis Major Musculocutaneous Flap Surgery for Oromandibular Reconstruction.

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.

Postradiotherapy Dental Implant Insertion Into Bone Grafts Harvested From Nonirradiated Tissue: Case Reports.

BACKGROUND: Prostheses and dental implants are often used to aid oral rehabilitation after surgery (with/without radiotherapy) for oral cancer. However, some studies have reported that the insertion of dental implants into irradiated bone results in a higher frequency of implant failure than the insertion of such implants in nonirradiated bone. MATERIALS AND METHODS: This report describes the cases of 4 patients with oral cancer who underwent surgery and radiotherapy (total dose: 50-86 Gy) and then had dental implants inserted within the irradiated area. In each case, an ilium bone graft or a latissimus dorsi myocutaneous flap containing scapular bone was transferred to the dental implant site before the insertion of the implants. RESULTS: Twenty-three implants were inserted. After loading, 2 implants were lost, and 21 remained stable. CONCLUSION: In patients who have undergone radiotherapy for oral cancer, transferring bone grafts harvested from nonirradiated tissue to the irradiated site before implant insertion might help to improve dental implant survival rates.

Multicenter Retrospective Study of Adjuvant Therapy for Patients with Pathologically Lymph Node-Positive Oral Squamous Cell Carcinoma: Analysis of Covariance Using Propensity Score.

BACKGROUND: The presence of pathologically positive lymph nodes (pN+) is a well-known prognostic factor in oral squamous cell carcinoma (OSCC). The aims of this retrospective multicenter study were to assess the prognosis of OSCC patients with pN+ disease; to compare the prognosis of patients with pN+ disease who underwent surgery plus radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) with that of patients who underwent surgery only; and to account for biases associated with treatment selection of adjuvant RT or CCRT. METHODS: The records of 313 OSCC patients with pN+ disease were retrospectively reviewed. The main outcome measures were 5-year disease-specific survival (DSS) and overall survival (OS) rates. To reduce selection biases associated with retrospective data, the treatment groups were evaluated by Cox proportional hazard analysis with propensity score as a covariate. RESULTS: The 5-year OS and DSS survival rates for the entire patient cohort were 51.8 and 59.2 %, respectively. T3-4 stage, closed (<5 mm) margin distance, ≥4 involved nodes, and extracapsular spread were significant poor prognostic factors for OS and DSS. In the propensity score analysis, postoperative RT/CCRT significantly improved OS and DSS compared to surgery only. However, OS and DSS were not significantly different between patients who received postoperative RT and CCRT. CONCLUSION: The addition of cytotoxic chemotherapy to RT does not provide additional survival benefit in OSCC patients with pN+ disease. Alternative strategies, such as molecular targeted therapies, are needed to further improve the survival of high-risk OSCC patients with pN+ disease.