Risk factors associated with prognosis of patients with medication-related osteonecrosis of the jaw.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive and/or antiangiogenic agents. As the treatment application for MRONJ is controversial, we aimed to identify the risk factors for poor prognosis and to help determine appropriate management. METHODS: This study included 119 patients. Relevant clinical data were obtained for all the patients. In computed tomography images, osteosclerosis, osteolysis, cortical perforation (buccal or lingual), periosteal reaction, and sequestration were evaluated. RESULTS: Multivariate analyses showed statistically significant associations between poor prognosis in patients with MRONJ and conservative treatment alone (hazard ratio [HR] 1.89), osteolysis (HR 4.67), and the absence of sequestration (HR 5.33). CONCLUSIONS: Conservative treatment alone without clear objectives needs to be avoided, and osteolytic change could be the criteria for surgical intervention. As the boundary between the lesion and vital bone is indistinct, we recommend extensive surgery in cases with unpredictable sequestration.

Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice.

Introduction: Occlusal disharmony induced by deteriorating oral health conditions, such as tooth loss and decreased masticatory muscle due to sarcopenia, is one of the causes of cognitive impairment. Chewing is an essential oral function for maintaining cognitive function not only in the elderly but also in young people. Malocclusion is an occlusal disharmony that commonly occurs in children. The connection between a decline in cognitive function and malocclusion in children has been shown with chronic mouth breathing, obstructive sleep apnea syndrome, and thumb/digit sucking habits. However, the mechanism of malocclusion-induced cognitive decline is not fully understood. We recently reported an association between feeding-related neuropeptides and cognitive decline in adolescent mice with activity-based anorexia. The aim of the present study was to assess the effects of malocclusion on cognitive behavior and clarify the connection between cognitive decline and hypothalamic feeding-related neuropeptides in adolescent mice with malocclusion. Methods: Four-week-old mice were randomly assigned to the sham-operated solid diet-fed (Sham/solid), sham-operated powder diet-fed (Sham/powder), or malocclusion-operated powder diet-fed (Malocclusion/powder) group. We applied composite resin to the mandibular anterior teeth to simulate malocclusion. We evaluated cognitive behavior using a novel object recognition (NOR) test, measured hypothalamic feeding-related neuropeptide mRNA expression levels, and enumerated c-Fos-positive cells in the hypothalamus 1 month after surgery. We also evaluated the effects of central antibody administration on cognitive behavior impairment in the NOR test. Results: The NOR indices were lower and the agouti-related peptide (AgRP) mRNA levels and number of c-Fos-positive cells were higher in the malocclusion/powder group than in the other groups. The c-Fos-positive cells were also AgRP-positive. We observed that the central administration of anti-AgRP antibody significantly increased the NOR indices. Discussion: The present study suggests that elevated cerebral AgRP signaling contributes to malocclusion-induced cognitive decline in adolescents, and the suppression of AgRP signaling can be a new therapeutic target against cognitive decline in occlusal disharmony.

Risk factors for pathological fracture in patients with mandibular osteoradionecrosis.

Osteoradionecrosis (ORN) often results in pathological fractures through progression. We aimed to identify the risk factors for pathological fracture in patients with mandibular ORN. Seventy-four patients with mandibular ORN were included in this retrospective study. We investigated various risk factors for pathological fracture in patients with mandibular ORN, including number of mandibular teeth with a poor prognosis each at initial evaluation before radiation therapy (RT) and when fracture occurred, and the proportion of antibiotic administration period in a follow-up duration after RT. The rate of occurrence of pathological fractures in patients with mandibular ORN was 25.7%. The median of duration between RT completion and fracture occurrence was 74.0 months. We found that pathological fracture was significantly associated with a larger number of mandibular teeth with a poor prognosis at initial evaluation before RT (P = 0.024) and when fracture occurred (P = 0.009). Especially, a larger number of mandibular teeth with P4 periodontitis, in other words severe periodontal status, was related to pathological fracture in both timings. The proportion of antibiotic administration period in a follow-up duration was also significant risk factor (P = 0.002). Multivariate analyses showed statistically significant associations between pathological fracture and a larger number of mandibular teeth with a poor prognosis when fracture occurred (hazard ratio 3.669). The patient with a larger number of mandibular teeth with P4 periodontitis may have a risk of not only occurrence of ORN but resulting in pathological fracture by accumulation of infection. Surgeons should consider extraction of those teeth regardless of before/after RT if necessary for infection control.

Factors Associated with Treatment Outcomes and Pathological Features in Patients with Osteoradionecrosis: A Retrospective Study.

A standard treatment for osteoradionecrosis (ORN) has not yet been established because of the diversity. Therefore, identifying the risk factors for a poor prognosis is essential. This study retrospectively investigated the factors associated with the prognosis of ORN in 68 patients. Relevant clinical data of all patients were obtained. Of the patients, 16 who underwent extensive surgery underwent histopathological analysis. The necrotic changes of the anterior and posterior margins in the cortical and cancellous bones were investigated. Multivariate analyses showed statistically significant associations between poor prognosis in patients with ORN and high radiation dose (hazard ratio [HR] 1.15), orocutaneous fistula (HR 2.93), and absence of sequestration (HR 2.49). Histopathological analysis showed a viable anterior margin of the middle portion of the cortical bone for all recovered cases; in contrast, most cases (75%) with a poor prognosis showed necrotic changes. The anterior margin of the cancellous bone was viable and resilient to high irradiation, regardless of the prognosis. These results suggest that patients with orocutaneous fistula should receive early surgical intervention, even if the affected area is limited or asymptomatic. In extensive surgery, a sufficient safety margin of necrotic bone, particularly in the anterior region, is required to improve the prognosis.

Strategy for preventing skin paddle necrosis in mandibular reconstruction with free fibula osteocutaneous flap.

BACKGROUND: Non-thrombotic skin paddle necrosis occasionally occurs during mandibular reconstructions with free fibula osteocutaneous flaps. The number of perforators, size of the skin paddle, and ischemia time of the flap are considered as causes of skin paddle necrosis. The importance of donor side selection has also been highlighted. This study aimed to investigate the leading cause of skin paddle necrosis and the optimal reconstructive procedure. METHODS: A total of 66 patients who underwent mandibular reconstruction using a free fibula osteocutaneous flap were retrospectively analyzed. Skin paddle necrosis, number of cutaneous perforators, size of the skin paddle, and ischemia time of the flap were investigated. An incorrect "laterality" was defined as a skin paddle (septum) covering the reconstruction plate. Donor-site morbidity was recorded. RESULTS: Skin paddle necrosis occurred in 15.2% of patients. An incorrect laterality was associated with a higher incidence of skin paddle necrosis (odds ratio, 22.0; 95% confidence interval, 2.5-195; p = .005). Donor-site morbidity was noted in 18.8% of the patients, without any significant difference in terms of the donor side with and without skin graft (p = .592). The postoperative activities of daily living were not affected. CONCLUSIONS: To prevent skin paddle necrosis, donor side selection is an important safety strategy during mandibular reconstruction with free fibula osteocutaneous flap. The postoperative activities of daily living were found to be little affected by differences in the donor side.

Risk factors associated with post-extraction bleeding in patients on warfarin or direct-acting oral anticoagulants: a retrospective cohort study.

PURPOSE: The purpose of this study was to investigate the risk factors associated with post-extraction persistent bleeding in patients on warfarin or direct-acting oral anticoagulants (DOACs) and the ability of risk scores to predict post-extraction bleeding. METHODS: Three hundred ninety-one patients taking warfarin or DOACs underwent tooth extractions. Various risk factors for post-extraction bleeding, including number of tooth extraction, with antiplatelet therapy, and risk scores, were investigated by univariate and multivariate analyses. A post-extraction bleeding was classified into grades 1-3. RESULTS: The incidence of post-extraction bleeding was 26.8% (77 out of 287 patients; grade 1: 63, grade 2:14) in patients taking warfarin, and 26.0% (27 out of 104 patients; grade 1: 20, grade 2:7) in patients taking warfarin DOACs. Multivariate analyses showed that multiple teeth extractions and HAS-BLED scores (above 3 points) in patients taking warfarin, and only multiple teeth extractions in patients taking DOAC, were significantly associated with post-extraction bleeding, respectively. CONCLUSION: Most of the post-extraction bleedings were grade 1, which can be stopped by eligibly pressing gauze by surgeons. If patients taking anticoagulants are scheduled to undergo multiple teeth extractions or their HAS-BLED score are above 3 points (if warfarin), we recommend informing patients risk of post-extraction bleeding before operation, taking carefully hemostasis, and instructing patients to bite down accurately on the gauze for longer than usual.

Peripheral facial nerve schwannoma at the inferior mandibular margin: a case report.

Schwannomas commonly occur in the head and neck region as acoustic neuromas. Facial nerve schwannomas are rare and usually occur in the temporal region. A 57-year-old woman presented with a mass at the right mandibular margin. Magnetic resonance imaging revealed a schwannoma located immediately caudal to the mental foramen. We were initially uncertain whether it arose from the trigeminal nerve or the facial nerve. Excision was performed under general anesthesia. The mass was encapsulated and easily detached from the surrounding tissue. The nerve of origin was identified proximal to the tumor. A facial nerve origin was confirmed as the muscles supplied by the marginal mandibular branch of the facial nerve moved on nerve stimulation. Nerve fibers were not found distal to the tumor, possibly because they had been cut during excision. We believe that this is the first report of a schwannoma arising from the peripheral facial nerve.

Occurrence and Treatment Outcome of Late Complications After Free Fibula Flap Reconstruction for Mandibular Osteoradionecrosis.

PURPOSE: This study aimed to evaluate the occurrence and treatment outcome of late complications after free fibula osteocutaneous flap reconstruction for mandibular osteoradionecrosis (ORN). METHODS: We enrolled 15 consecutive patients (14 men, one woman; median age 65 years, range 57-80 years) who underwent free fibula reconstruction for advanced mandibular ORN during 2013-2017 with two or more years of follow-up. Late complications included infection, plate exposure, and recurrence at the resection margin. The effect of perioperative antibiotic administration on late complications was also assessed. RESULTS: Late complications occurred in 33.3% (5/15) of patients, including two infections (local and distant), two plate exposures, and two recurrences (plate exposure and recurrence occurred in one patient). Perioperative antibiotic administration duration did not significantly affect the occurrence of postoperative late complications. All late complications were treated without problems. CONCLUSIONS: Late complications after ORN reconstructive surgery are not uncommon, but can be treated properly.

Effect of educational intervention on the appropriate use of oral antimicrobials in oral and maxillofacial surgery: a retrospective secondary data analysis.

BACKGROUND: In Japan, oral third-generation cephalosporins with broad-spectrum activity are commonly prescribed in the practices of dentistry and oral surgery. However, there are few reports on the appropriate use of antibiotics in the field of oral surgery. This study aimed to evaluate the appropriateness of antibiotic use before and after an educational intervention in the Department of Oral and Maxillofacial Surgery, Kobe University Hospital. METHODS: The use of oral antibiotics was investigated among inpatients and outpatients before and after an educational intervention conducted by the antimicrobial stewardship team. Additionally, the frequency of surgical site infection after the surgical removal of an impacted third mandibular molar under general anesthesia and the prevalence of adverse effects of the prescribed antibiotics were comparatively evaluated between 2013 and 2018. RESULTS: After the educational intervention, a remarkable reduction was noted in the prescription of oral third-generation cephalosporins, but increased use of penicillins was noted among outpatients. There was reduced use of macrolides and quinolones in outpatients. Although a similar trend was seen for inpatients, the use of quinolones increased in this population. Despite the change in the pattern of antibiotic prescription, inpatients who underwent mandibular third molar extraction between 2013 and 2018 did not show a significant increase in the prevalence of surgical site infections (6.2% vs. 1.8%, p = .336) and adverse effects of drugs (2.1% vs. 0%, p = .466). CONCLUSIONS: This study suggests that the judicious use of oral antibiotics is possible through conscious and habitual practice of appropriate antibiotic use. However, further investigation is required to develop measures for appropriate use of oral antibiotics.

Wire Myography for Continuous Estimation of the Optimal Concentration of Topical Lidocaine as a Vasodilator in Microsurgery.

BACKGROUND: Intraoperative vasospasm during reconstructive microvascular surgery is often unpredictable and may lead to devastating flap loss. Therefore, various vasodilators are used in reconstructive microsurgery to prevent and relieve vasospasm. Lidocaine is a vasodilator commonly used in microvascular surgery. Although many reports have described its in vitro and in vivo concentration-dependent vasodilatory effects, limited studies have examined the pharmacological effects of lidocaine on blood vessels in terms of persistence and titer. METHODS: In this study, the vasodilatory effect of lidocaine was examined by using the wire myograph system. Abdominal aortas were harvested from female rats, sliced into rings of 1-mm thickness, and mounted in the wire myograph system. Next, 10, 5, 2, and 1% lidocaine solutions were applied to the artery, and the change in vasodilation force, persistence of the force, and time required to reach equilibrium were measured. RESULTS: The vasodilatory effect was confirmed in all groups following lidocaine treatment. Although strong vasodilation was observed in the 10% lidocaine group, it was accompanied by irreversible degeneration of the artery. Vasodilation in the 1% lidocaine group was weaker than that in the other groups 500 seconds after lidocaine addition (p < 0.05). Between the 5 and 2% lidocaine groups, 5% lidocaine showed a stronger vasodilatory effect 400 to 600 seconds after lidocaine addition (p < 0.01); however, there was no significant difference in these groups after 700 seconds. Additionally, there was no difference in the time required for the relaxation force to reach equilibrium among the 5, 2, and 1% lidocaine groups. CONCLUSION: Although our study confirmed the dose-dependent vasodilatory effect of lidocaine, 5% lidocaine showed the best vasodilatory effect and continuity with minimal irreversible changes in the arterial tissue.

Which symptoms negatively affect the oral health-related quality of life in patients with osteonecrosis of the jaw?

OBJECTIVES: One of the treatment goals for osteonecrotic lesions of the jaw, such as medication-related osteonecrosis of the jaw (MRONJ) or osteoradionecrosis (ORN), is restoration of quality of life (QOL). This study aimed to identify symptoms that negatively affect QOL in patients with unhealed MRONJ or ORN. STUDY DESIGN: This cross-sectional study included patients who were previously diagnosed with MRONJ or ORN and who underwent treatment at the Kobe University Hospital between June 2015 and February 2016. Patient QOL was measured by using the Oral Health Impact Profile (OHIP-14). The predictor variable was disease status (stage and healing). The outcome variable was OHIP-14. One-way analysis of variance and Tukey's test were performed. RESULTS: The study included 74 patients (37 men and 37 women; mean age 70 years). Although there was no significant difference between the OHIP-14 scores of unhealed MRONJ and ORN (stages 1-3) and those of healed ones, the "worsened sense of taste" resulted in significant differences among stages in patients with unhealed MRONJ (P = .027) and the "painful mouth aching" in patients with unhealed ORN (P = .041). CONCLUSIONS: Worsened sense of taste and pain negatively affected QOL in patients with unhealed MRONJ and ORN.

Neutrophil-lymphocyte ratio associated with poor prognosis in oral cancer: a retrospective study.

BACKGROUND: Prognostic biomarkers provide essential information about a patient's overall outcome. However, existing biomarkers are limited in terms of either sample collection, such as requiring tissue specimens, or the process, such as prolonged time for analysis. In view of the need for convenient and non-invasive prognostic biomarkers for oral cancer, we aimed to investigate the prognostic values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patient survival. We also aimed to explore the associations of these ratios with the clinicopathologic characteristics of Japanese oral squamous cell carcinoma patients. METHODS: This study was a non-randomized retrospective cohort study in a tertiary referral center. We included 433 patients (246 men, 187 women) who underwent radical surgery for oral cancers between January 2001 and December 2013. We evaluated various risk factors for poor prognosis including neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio with univariate and multivariate analyses. The disease-specific survival and overall survival rates of patients were compared among the factors and biomarkers. RESULTS: In multivariable Cox proportional hazards analysis, high neutrophil-to-lymphocyte ratio (hazard ratio 2.87, 95% confidence interval 1.59-5.19, P <  0.001), moderately or poorly differentiated histology (hazard ratio 2.37, 95% confidence interval 1.32-4.25, P <  0.001), and extranodal extension (hazard ratio 1.95, 95% confidence interval 1.13-3.35, P = 0.016) were independent predictors of disease-specific survival. High neutrophil-to-lymphocyte ratio (hazard ratio 2.30, 95% confidence interval 1.42-3.72, P <  0.001), moderately or poorly differentiated (hazard ratio 1.72, 95% confidence interval 1.07-2.76, P = 0.025), and extranodal extension (hazard ratio 1.79, 95% confidence interval 1.13-2.84, P = 0.013) were independent predictors of overall survival. CONCLUSIONS: Neutrophil-to-lymphocyte ratio might be a potential independent prognostic factor in Japanese oral squamous cell carcinoma patients.

Effect of size difference between hemiglossectomy and reconstruction flap on oral functions: A retrospective cohort study.

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.

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.

Perioperative intervention by oral medicine team in cardiovascular surgery 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.

A literature review of perioperative antibiotic administration in surgery for medication-related osteonecrosis of the jaw.

PURPOSE: Few studies exist that focus on the details of perioperative antibiotic administration for surgery to treat medication-related osteonecrosis of the jaw (MRONJ). The regime and duration of perioperative antibiotics applied in published studies were reviewed to clarify appropriate perioperative antibiotic use in MRONJ surgery. METHODS: A literature search was conducted using the MEDLINE database via PubMed. RESULTS: The search resulted in 453 hits on PubMed. After reading the downloaded full-text articles, 17 articles met the inclusion and exclusion criteria. The most common perioperative antibiotic used for MRONJ surgery was a combination of penicillin-based antibiotics and ß-lactamase inhibitor (52.9%), and the second most common regime was penicillin-based antibiotics with metronidazole (17.6%). The duration of administration was 2 weeks postoperatively in nine studies, whereas four studies applied long-term administration (2-6 weeks postoperatively). CONCLUSIONS: Oral and maxillofacial surgeons mostly prefer penicillin-based antibiotics plus ß-lactamase inhibitor or metronidazole for MRONJ surgery. The duration of administration of these medications may be based on empirical experience.

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.

Ionizing Radiation Enhances Paracellular Permeability Through Alteration of Intercellular Junctions in Cultured Human Lymphatic Endothelial Cells.

BACKGROUND: A problematic complication after radiation therapy is lymphedema. Development of lymphedema is associated with an increase in lymphatic paracellular permeability. The current study investigated the effects of radiation on intercellular junctions and paracellular permeability in cultured human dermal lymphatic endothelial cells (HDLECs). METHODS AND RESULTS: Double immunofluorescence staining with vascular endothelial (VE)-cadherin and actin immediately after X-ray irradiation (5 or 20 Gy) was performed. Morphological changes induced by irradiation were assessed. Cell viability and paracellular permeability after irradiation were also evaluated. Broad junctions in which VE-cadherin was accumulated at cell-cell contacts and almost colocalized with actin were significantly decreased in a dose-dependent manner in confluent and sparse irradiated HDLECs. Irradiation shortened the width of VE-cadherin-positive areas at the cell-cell contacts. Actin filaments did not colocalize with VE-cadherin after 20 Gy irradiation. Although cell viability was not affected by irradiation, paracellular permeability significantly increased in a dose-dependent manner. CONCLUSIONS: A dose of 5 or 20 Gy irradiation in HDLECs does not affect cell viability, but changes VE-cadherin mediated intercellular junctions and actin structure, resulting in an increase of paracellular permeability. Further investigations on the regulatory proteins involved in radiation-induced changes, which were observed in the current study, may contribute to development of lymphedema therapy.

Association between pain severity and clinicohistopathologic findings in the mandibular canal and inferior alveolar nerve of patients with advanced mandibular osteoradionecrosis.

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.

Potential role of post-treatment follow-up FDG-PET CT to detect mandibular osteoradionecrosis: A case report.

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.