Intraoral Styloidectomy Using an Endoscope With Tissue Retractor.

ABSTRACT: The extraoral approach with the risk of facial nerve injury and the visible scar is commonly performed for an elongated styloid process, because intraoral styloidectomy is challenging for the deep and limited surgical field. The authors report minimally invasive intraoral styloidectomy using an endoscope with tissue retractor. A 57-year-old female was referred to our department with a left pharyngeal foreign body sensation and pharyngeal pain after head turning and neck compression. Clinical and radiological diagnosis was an elongated styloid process (Eagle syndrome). Because the styloid process could be palpated intraorally, the patient underwent endoscopically-assisted intraoral styloidectomy without tonsillectomy under general anesthesia as minimally invasive surgery. The styloid process was resected safely with a piezoelectric surgical device under endoscopic guidance. The postoperative course was uneventful without complications.

Computational Fluid Simulation of Fibrinogen around Dental Implant Surfaces.

Ultraviolet treatment of titanium implants makes their surfaces hydrophilic and enhances osseointegration. However, the mechanism is not fully understood. This study hypothesizes that the recruitment of fibrinogen, a critical molecule for blood clot formation and wound healing, is influenced by the degrees of hydrophilicity/hydrophobicity of the implant surfaces. Computational fluid dynamics (CFD) implant models were created for fluid flow simulation. The hydrophilicity level was expressed by the contact angle between the implant surface and blood plasma, ranging from 5° (superhydrophilic), 30° (hydrophilic) to 50° and 70° (hydrophobic), and 100° (hydrorepellent). The mass of fibrinogen flowing into the implant interfacial zone (fibrinogen infiltration) increased in a time dependent manner, with a steeper slope for surfaces with greater hydrophilicity. The mass of blood plasma absorbed into the interfacial zone (blood plasma infiltration) was also promoted by the hydrophilic surfaces but it was rapid and non-time-dependent. There was no linear correlation between the fibrinogen infiltration rate and the blood plasma infiltration rate. These results suggest that hydrophilic implant surfaces promote both fibrinogen and blood plasma infiltration to their interface. However, the infiltration of the two components were not proportional, implying a selectively enhanced recruitment of fibrinogen by hydrophilic implant surfaces.

Hydrogen sulfide bypasses the rate-limiting oxygen activation of heme oxygenase.

Discovery of unidentified protein functions is of biological importance because it often provides new paradigms for many research areas. Mammalian heme oxygenase (HO) enzyme catalyzes the O2-dependent degradation of heme into carbon monoxide (CO), iron, and biliverdin through numerous reaction intermediates. Here, we report that H2S, a gaseous signaling molecule, is part of a novel reaction pathway that drastically alters HO's products, reaction mechanism, and catalytic properties. Our prediction of this interplay is based on the unique reactivity of H2S with one of the HO intermediates. We found that in the presence of H2S, HO produces new linear tetrapyrroles, which we identified as isomers of sulfur-containing biliverdin (SBV), and that only H2S, but not GSH, cysteine, and polysulfides, induces SBV formation. As BV is converted to bilirubin (BR), SBV is enzymatically reduced to sulfur-containing bilirubin (SBR), which shares similar properties such as antioxidative effects with normal BR. SBR was detected in culture media of mouse macrophages, confirming the existence of this H2S-induced reaction in mammalian cells. H2S reacted specifically with a ferric verdoheme intermediate of HO, and verdoheme cleavage proceeded through an O2-independent hydrolysis-like mechanism. This change in activation mode diminished O2 dependence of the overall HO activity, circumventing the rate-limiting O2 activation of HO. We propose that H2S could largely affect O2 sensing by mammalian HO, which is supposed to relay hypoxic signals by decreasing CO output to regulate cellular functions. Moreover, the novel H2S-induced reaction identified here helps sustain HO's heme-degrading and antioxidant-generating capacity under highly hypoxic conditions.

Daily Cisplatin and Weekly Docetaxel versus Weekly Cisplatin Intra-Arterial Chemoradiotherapy for Late T2-3 Tongue Cancer: A Pilot and Feasibility Trial.

Background and objectives: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in the present study. In the DIACRT group, 25 patients had late T2, and 20 patients had T3. A total of nine patients had late T2 and two had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months, respectively. The five-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for the DIACRT group, and 60.6% and 63.6% for the WIACRT group, respectively. The LC rate and OS of the DIACRT group were significantly higher than those of the WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods in both groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Raltegravir Potassium.

The present monograph discusses the possibility of BCS-based biowaivers for immediate release pharmaceutical products containing raltegravir potassium, which is used to treat human immunodeficiency virus (HIV) infections. Raltegravir potassium can be assigned to BCS class II or IV since this compound has low solubility and uncertain permeability. Therefore, according to the ICH M9 guideline, it is not recommended to apply BCS-based biowaiver to approval of immediate release solid dosage forms of raltegravir potassium, either for new generic versions or when moderate to major changes in composition and/or the manufacturing method of the product are made.

Thermochemoradiotherapy Using Superselective Intra-arterial Infusion for Patients With Oral Cancer With Cervical Lymph Node Metastases.

AIM: We aimed to retrospectively investigate the outcomes and pathological effects of retrograde superselective intra-arterial chemoradiotherapy (IACRT) combined with hyperthermia on metastatic lymph nodes of patients with oral squamous cell carcinoma. PATIENTS AND METHODS: Patients with lymph node metastasis from oral cancer were treated with IACRT using cisplatin plus docetaxel combined with hyperthermia prior to surgical removal 8 weeks after completion of IACRT and hyperthermia. The locoregional control and overall survival rates were calculated using the Kaplan-Meier method. RESULTS: A total of 35 patients received the combination therapy of whom 26 received it as definitive treatment and in the rest, it was administered as preoperative treatment. The 5-year locoregional control and overall survivaI rates were 95.6% and 80.2% in the definitive-treatment group, and 100% and 66.6% in the preoperative-treatment group, respectively. CONCLUSION: The combination therapy provided good outcomes in patients with lymph node metastases from advanced oral cancer.

Prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma treated by intra-arterial infusion chemotherapy concurrent with radiotherapy.

BACKGROUND: The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy. METHODS: A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m2 docetaxel and 150 mg/m2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks. RESULTS: The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P < .05). No grade 5 toxicities were observed. CONCLUSIONS: Intra-arterial infusion chemotherapy concurrent with radiotherapy was effective for advanced maxillary gingival SCC.

Multidisciplinary approach for treatment of a dentigerous cyst - marsupialization, orthodontic treatment, and implant placement: a case report.

BACKGROUND: Dentigerous cysts are common odontogenic cysts associated with unerupted teeth. We describe a previously unreported case of a multidisciplinary approach using surgical, orthodontic, and implant treatment to establish the occlusion for a patient with a maxillary dentigerous cyst. CASE PRESENTATION: An 18-year-old Japanese woman visited our hospital with a chief complaint of gingival swelling in her anterior maxillary region, midline diastema, and tooth crowding. Her main symptom was this gingival swelling. A panoramic radiograph revealed a radiolucent area, 30 mm in diameter, round in shape, and with well-demarcated margins including the maxillary canine. Computed tomography revealed a cystic cavity filled with homogeneous fluid of the same density as water, and a distolingually inclined canine. Our clinical diagnosis was maxillary dentigerous cyst with an unerupted distolingually inclined canine. The selected treatment was marsupialization of the dentigerous cyst, followed by orthodontic traction of the unerupted canine, and simultaneous orthodontic treatment of the midline diastema and tooth crowding. The orthodontic traction failed because the canine did not erupt completely, and the canine was extracted. The treatment plan was then changed to implant treatment after the tooth crowding and midline diastema had been improved. Because the alveolar ridge width was inadequate, the implant was placed after a two-stage implant treatment; therefore, a satisfactory occlusion could be achieved. Our patient did not experience any complications, and the cyst has not recurred. A radiograph taken 7 years after marsupialization of the dentigerous cyst revealed that the cystic cavity had been replaced by new bone. CONCLUSIONS: In general, orthodontic traction of an unerupted tooth after marsupialization should be the best option. However, if orthodontic traction fails, a multidisciplinary approach involving implant treatment may be necessary. We describe a case in which a multidisciplinary approach involving surgical, orthodontic, and implant treatment was used to establish a satisfactory occlusion for a patient with a dentigerous cyst.

Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: Analysis of therapeutic results in 118 cases.

OBJECTIVES: To evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy. MATERIALS AND METHODS: Between June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50-70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50-70 mg/m2; cisplatin, total 125-175 mg/m2) for 5-7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox's proportional hazards model was used for both univariate and multivariate analyses. RESULTS: The median follow-up for all patients was 38.5 months (range, 3-129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification. CONCLUSION: Retrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.

Treatment of oral cancer using magnetized paclitaxel.

N,N'-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/quantitation of drug distribution.

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for T2-4N0 tongue cancer: control of occult neck metastasis.

OBJECTIVE: To evaluate the therapeutic results and control of occult neck metastasis in patients with T2-4N0 oral tongue squamous cell carcinoma treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. STUDY DESIGN: Forty-two patients with T2-4N0 tongue cancer (17 with late T2; 13 with T3; and 12 with T4a disease, M0) were treated with intra-arterial chemoradiotherapy. Treatment consisted of retrograde superselective intra-arterial chemotherapy (docetaxel 50-70 mg/m2, cisplatin 125-175 mg/m2) and daily concurrent radiotherapy (50-70 Gy) for 5-7 weeks. RESULTS: The median follow-up for all patients was 46.5 months (range, 8-105 months). Primary-site complete response was achieved in 42 of 42 cases (100%). Three-year overall survival, progression-free survival, and local control rates were 85.0%, 77.8%, and 91.7%, respectively. Delayed neck metastasis was detected in 5 of 42 cases (11.9%). Grade 3 or 4 toxic changes included oral mucositis in 92.9%, neutropenia in 21.4%, and thrombocytopenia in 4.8%. Grade 3 toxicities included anemia in 16.7%, radiation dermatitis in 9.5%, nausea in 4.8%, and fever in 2.4%. CONCLUSIONS: Retrograde superselective intra-arterial chemotherapy for T2-4N0 tongue cancer provided good overall survival and local control rates and was effective for occult neck metastasis.

Clinical outcomes of retrograde intra-arterial chemotherapy concurrent with radiotherapy for elderly oral squamous cell carcinoma patients aged over 80 years old.

BACKGROUND: The aim of this retrospective observational study was to evaluate toxicities, overall survival, and locoregional control in elderly oral squamous cell carcinoma patients who had undergone retrograde intra-arterial chemotherapy combined with radiotherapy. METHODS: Thirty-one elderly patients over 80 years old with oral squamous cell carcinoma were enrolled in present study. The treatment schedule consisted of intra- arterial chemotherapy (docetaxel, total 60 mg/m2; cisplatin, total 150 mg/m2) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. RESULTS: The median patient age was 82.5 years old (range, 80-88 years). Of the 31 patients, six (19%) had stage II, 6 (19%) had stage III, 17 (55%) had stage IVA, and 2 (6%) had stage IVB. The median follow-up period for all patients was 37 months (range, 7-86 months). The 3-year overall survival and locoregional control rates were 78% and 81%, respectively. The major acute grade 3 adverse events were oral mucositis in 22 (71%) patients, neutropenia in 16 (52%), and dermatitis in 11 (35%). With respect to late toxicities, 1 patient (3%) developed grade 3 osteoradionecrosis of the jaw. No grade 4 or higher toxicities were observed during the treatment and follow-up periods. CONCLUSIONS: Retrograde intra-arterial chemotherapy combined with radiotherapy was effective in improving overall survival and locoregional control even for elderly patients.

[Clinical phase trial of concurrent chemoradiotherapy combined TS-1 and nedaplatin].

We have treated head and neck carcinoma by concurrent chemoradiotherapy combined with 5-fluorouracil (5-FU) and cisplatin (CDDP). However,this chemoradiotherapy could not show an enormous effect in the advanced carcinoma of Stage III and IV. Therefore,we changed the contents of the chemotherapy, i.e., we replaced 5-FU, one of the agents with time dependency, to continuous administration of TS-1 for 2 weeks,also replacing CDDP, one of the agents with dose dependency, to nedaplatin (CDGP) in order to reduce kidney dysfunction. In this concurrent chemoradiotherapy, oral TS-1 was continued for 2 weeks and CDGP was administered on the 4 th day from the start of TS-1. In addition, radiotherapy was performed concurrently. In this way,we performed a phase I clinical trial of concurrent chemoradiotherapy combining TS-1 and nedaplatin (CDGP). As for the incidence of adverse events,grade 3 mucositis due to radiation was observed in two patients. As a result of the phase I clinical trial,we decided the maximum-tolerated dose (MTD) of TS-1 to be 80 mg/m2 (maximum 120 mg/body) and 100 mg/m2 for CDGP, and then determined the recommended dose(RD) of TS-1 as 80 mg/m2 (maximum 120 mg/ body) TS-1 and of CDGP as 9 0 mg/m2 CDGP.

Producing Capabilities of Interferon-gamma and Interleukin-10 in Peripheral Blood from Oral Squamous Cell Carcinoma Patients.

In order to evaluate the Th1 and Th2 responses of Oral Squamous Cell Carcinoma (OSCC) patients, we investigated the cytokine producing capability of peripheral blood (PB), and compared it with clinicopathological appearances of OSCC patients. The production of a Th1-type cytokine, interferon (IFN)-γ, from lipopolysaccharide (LPS)-stimulated PB correlated positively with the frequency of lymph node metastasis. We also investigated the production of a Th2-type cytokine, IL-10, however, no significant correlation was observed with the clinicopathological appearances. Our results suggested that the IFN-γ producing capability was specifically regulated and dependent on the regional metastatic potencies of OSCCs.

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: analysis of therapeutic results in 112 cases.

PURPOSE: To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. MATERIALS AND METHODS: One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60mg/m(2), cisplatin, total 150mg/m(2)) and daily concurrent radiotherapy (total of 60Gy) for 6 weeks. RESULTS: The median follow-up for all patients was 46.2 months (range, 10-76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients. CONCLUSION: Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control.

Increase of peripheral blood CD57+ T-cells in patients with oral squamous cell carcinoma.

BACKGROUND/AIM: The subset of T-cells positive for expression of cluster of differentiation (CD) 57 has been associated with various cancer phenotypes. However, the presence of CD57(+) T-cells in patients with oral squamous cell carcinoma (OSCC) has yet to be confirmed. In the present study, we examined the diagnostic significance of the presence of CD57(+) T-cells in peripheral blood (PB) from patients with OSCC. MATERIALS AND METHODS: The subset of CD57(+) T-cells in PB was analyzed in 43 patients with OSCC by fluorescence-activated cell sorting (FACS) analysis. RESULTS: The proportion of CD57(+) T-cells, including both CD8(+) and CD4(+) subsets, significantly increased with clinical stage, especially in parallel with tumor size. CONCLUSION: Our results suggest that an increase in the population of CD57(+) T-cells is a potent prognostic marker and may also influence the systemic immunity of patients with OSCC.

Thermochemoradiation therapy using superselective intra-arterial infusion via superficial temporal and occipital arteries for oral cancer with N3 cervical lymph node metastases.

PURPOSE: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. METHODS AND MATERIALS: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m(2); CDDP, total 100-150 mg/m(2)) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks. RESULTS: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. CONCLUSIONS: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3 metastatic lymph nodes experienced a high rate of distant metastases.