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Patients with squamous cell carcinoma (SCC) of the head and neck including the oral cavity have a high risk of upper gastrointestinal cancer, especially esophageal cancer. Synchronous upper gastrointestinal cancers affect the field of radiation or surgery, and undetected double cancer can cause poor prognosis. The purpose of this retrospective study was to evaluate the diagnostic performance of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting synchronous upper gastrointestinal cancer at the initial staging of oral cancer patients. Between September 2006 and August 2021, 804 newly diagnosed oral squamous cell carcinoma patients who undergo esophagogastroduodenoscopy (EGD) and FDG-PET/CT at the initial staging were enrolled in this study. The incidence of synchronous upper gastrointestinal cancer in EGD screening at the initial staging of oral cancer was retrospectively calculated. Furthermore, we evaluated the diagnostic performance of FDG-PET/CT for screening of synchronous upper gastrointestinal cancer in oral cancer patients. The incidence of synchronous upper gastrointestinal cancer in EGD screening at the initial staging of oral cancer was 4.2% (34/804 patients). Of 34 oral cancer patients with synchronous upper gastrointestinal cancer, 26 (76.5%) had both smoking and drinking habits. The sensitivity, specificity, accuracy, false-negative rate, false-positive rate, positive predictive value, and negative predictive value of FDG-PET/CT for synchronous upper gastrointestinal cancer were 44.1%, 99.6%, 97.3%, 55.9%, 0.4%, 83.3%, and 97.6%, respectively. Because PET/CT cannot sufficiently detect synchronous upper gastrointestinal cancer in oral SCC patients, EGD screening before the treatment may be suitable for the high-risk oral SCC patients. [ABSTRACT FROM AUTHOR]

Objectives: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. Materials and Methods: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression‐free and overall survival. Progression‐free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression‐free and overall survival were identified using multivariate analysis. Results: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1‐ and 2‐year progression‐free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression‐free survival were performance status and immune‐related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune‐related adverse events. Conclusion: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients. [ABSTRACT FROM AUTHOR]

Superselective intra-arterial chemotherapy (SSIAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, the agent distribution between the lingual artery and facial artery (FA) is not clear in SSIAC for patients with the linguofacial trunk. The agent distribution in the SSIAC method was investigated using computational fluid dynamics (CFD). Ten three-dimensional vessel models were created from CT images of two patients with oral cancer (patients A and B) with the linguofacial trunk. Catheter models were combined with vessel models to mimic intra-arterial infusion, and the agent flow was analyzed. In patient A models, the agent distribution varied depending on the catheter tip position in the linguofacial trunk, while all anticancer agents flowed into the FA only in patient B models. This study revealed that the behavior of the agent in the common trunk is determined by the blood flow field which depends on the topography of the vessels in each patient. Therefore, the catheter tip position should be changed according to the vessel topography to deliver anticancer agents into the tumor-feeding artery. Moreover, CFD can be a useful method to predict the agent flow for each patient before SSIAC. [ABSTRACT FROM AUTHOR]

The EP4 prostanoid receptors are one of four receptor subtypes for prostaglandin E2 (PGE2). Therefore, EP4 may play an important role in cancer progression. However, little information is available regarding their function per se, including migration and the cellular signaling pathway of EP4 in oral cancer. First, we found that mRNA and protein expression of EP4 was abundantly expressed in human‐derived tongue squamous cell carcinoma cell lines HSC‐3 and OSC‐19. The EP4 agonist (ONO‐AE1‐437) significantly promoted cell migration in HSC‐3 cells. In contrast, knockdown of EP4 reduced cell migration. Furthermore, we confirmed that knockdown of EP4 suppressed metastasis of oral cancer cells in the lungs of mice in vivo. Therefore, we focused on the mechanism of migration/metastasis in EP4 signaling. Interestingly, EP4 agonist significantly induced intracellular Ca2+ elevation not in only oral cancer cells but also in other cells, including normal cells. Furthermore, we found that EP4 activated PI3K and induced Ca2+ influx through Orai1 without activation of store depletion and stromal interaction molecule 1 (STIM1). Immunoprecipitation showed that EP4 formed complexes with Orai1 and TRPC1, but not with STIM. Moreover, the EP4 agonist ONO‐AE1‐437 phosphorylated ERK and activated MMP‐2 and MMP‐9. Knockdown of Orai1 negated EP4 agonist‐induced ERK phosphorylation. Taken together, our data suggested that EP4 activated PI3K and then induced Ca2+ influx from the extracellular space through Orai1, resulting in ERK phosphorylation and promoting cell migration. Migration is regulated by EP4/PI3K/Orai1 signaling in oral cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. Methods Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. Results For all patients, the median follow-up was 25 months (range, 3-77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. Conclusion Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Intra-arterial chemotherapy (IAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, distribution of anticancer agent into several branches of the external carotid artery (ECA) in IAC has not demonstrated sufficient treatment efficacy. To improve the effectiveness of IAC, the flow distribution of anticancer agent into the branches of the ECA in several IAC methods was investigated using computational fluid dynamics (CFD).Methods: Patient-specific three-dimensional vessel models were created from CT images of 2 patients with tongue cancer. Catheter models were combined with the vessel models. Thirty-two models were generated with varying vertical and horizontal positions of the catheter tip. With the use of a zero-dimensional resistance model of the peripheral vessel network, conventional IAC and superselective IAC were simulated in 30 and 2 models, respectively. The flow distribution of anticancer agent into the branches of the ECA was investigated in 32 models. Additionally, the blood streamline was traced from the inlet of the common carotid artery toward each outlet to examine the flow of anticancer agent in all models, and the wall shear stress of the vessel was calculated for some models.Results: The CFD simulations could be conducted within a reasonable computational time. In several models, the anticancer agent flowed into the target artery only when the catheter tip was located below the bifurcation of the ECA and each target artery. Furthermore, the anticancer agent tended to flow into the target artery when the catheter tip was shifted toward the target artery. In all ECA branches that had flow of anticancer agent, the blood streamlines to the target arteries contacted the catheter tip. Anticancer agent flowed into only the target artery in patients' models for superselective IAC. However, high wall shear stress was observed at the target artery in one patient's model.Conclusions: This CFD study showed that location of the catheter tip was important in controlling the anticancer agent in conventional IAC. The distribution rate of anticancer agent into the tumor-feeding artery tended to increase when the catheter tip was placed below and toward the target artery. Although superselective IAC can reliably supply anticancer agent to the target artery, high wall shear stress at the target artery can occur, depending on vessel geometry of the patient, which may cause serious complications during the treatment. [ABSTRACT FROM AUTHOR]

Background: Patient-specific modelling in clinical studies requires a realistic simulation to be performed within a reasonable computational time. The aim of this study was to develop simple but realistic outflow boundary conditions for patient-specific blood flow simulation which can be used to clarify the distribution of the anticancer agent in intra-arterial chemotherapy for oral cancer.Methods: In this study, the boundary conditions are expressed as a zero dimension (0D) resistance model of the peripheral vessel network based on the fractal characteristics of branching arteries combined with knowledge of the circulatory system and the energy minimization principle. This resistance model was applied to four patient-specific blood flow simulations at the region where the common carotid artery bifurcates into the internal and external carotid arteries.Results: Results of these simulations with the proposed boundary conditions were compared with the results of ultrasound measurements for the same patients. The pressure was found to be within the physiological range. The difference in velocity in the superficial temporal artery results in an error of 5.21 ± 0.78 % between the numerical results and the measurement data.Conclusions: The proposed outflow boundary conditions, therefore, constitute a simple resistance-based model and can be used for performing accurate simulations with commercial fluid dynamics software. [ABSTRACT FROM AUTHOR]

Abstract: 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/m2, cisplatin, total 150mg/m2) and daily concurrent radiotherapy (total of 60Gy) for 6weeks. Results: The median follow-up for all patients was 46.2months (range, 10–76months). 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. [Copyright &y& Elsevier]

Abstract: Malignancies associated with Behçet''s disease (BD) are rare, and surgery for patients with BD frequently results in postoperative complications such as wound dehiscence, postoperative infection, and exacerbation of BD itself. We present a rare case of left tongue carcinoma in a 70-year-old woman with BD. The pathological findings showed moderate-differentiated squamous cell carcinoma with atypical squamous cell infiltrative proliferation. Daily concurrent chemoradiotherapy with docetaxel and cisplatin using superselective intra-arterial infusion via superficial temporal artery and occipital artery was performed. Two indwelling catheters, one from the left occipital artery to the left lingual artery and the other from the left superficial temporal artery to the left facial artery, were inserted to carry out superselective intra-arterial infusion treatment. After completion of all treatments, a biopsy specimen of the primary lesion showed grade III, nonviable tumor cells, suggesting complete response. Superselective intra-arterial chemoradiotherapy was effective for treating the tongue carcinoma associated with BD, and avoided surgical treatment. This method could control the primary lesion and cervical lymph node metastasis clinically without severe side effects. The patient has been disease free for 18 months without the complication of treatment. [Copyright &y& Elsevier]

Abstract: We developed a rat model of oral cancer pain by inoculating cancer cells into the lower gingiva. A squamous cell carcinoma (SCC) derived from Fisher rats, SCC-158, was inoculated into the subperiosteal tissue on the lateral side of the lower gingiva in male Fisher rats. Inoculation of cancer cells induced marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve area. Infiltration of the tumor cells into the mandible and the completely encompassed inferior alveolar nerve was observed. Calcitonin gene–related peptide (CGRP)–, substance P (SP)–, ATP receptor (P2X3)–, and capsaicin receptor (TRPV1)–immunoreactive cells strikingly increased in the small-cell group of trigeminal ganglia (TGs) after tumor cell inoculation. The TRPV1-immunoreactive cells also increased in the medium- and large-cell groups. Retrograde tracing combined with immunofluorescence techniques revealed the increased expression of peptides and the receptors in maxillary nerve afferent neurons. These results suggest that inoculation of SCC cells into the lower gingiva produces mechanical allodynia and thermal hyperalgesia, indicating the establishment of a novel rat model of oral cancer pain. Increased expression of CGRP, SP, P2X3, and TRPV1 in the TG may be involved in the behavioral changes in this model. Perspective: To clarify the mechanisms of oral cancer pain, we examined the expression of calcitonin gene–related peptide, substance P, ATP receptor P2X3, and capsaicin receptor TRPV1 in trigeminal ganglia. Characterizations of these molecular systems which mediate pain perception are important to develop novel clinical tools for promoting relief of oral cancer pain.© 2006 by the American Pain Society [Copyright &y& Elsevier]

Objective: The purpose of this study was to evaluate the clinical efficacy, histopathological efficacy, and response to preoperative thermochemoradiotherapy for N[sub 3] cervical lymph node metastases of oral cancer. Methods: Preoperative thermochemoradiotherapy was performed in 8 patients with oral cancer and N[sub 3] cervical lymph node metastasis. These patients underwent four-weekly sessions of hyperthermia, combined with radiotherapy (40 Gy) as well as chemotherapy with cisplatin (CDDP; 100 mg/m[sup 2] ), all prior to surgery. Radical neck dissection was performed 4 weeks after completion of preoperative thermochemoradiotherapy. Results: The preoperative treatment of cervical lymph node metastases yielded a partial response in 6 patients, while 2 patients demonstrated no change. Histopathologically, grade III was detected in 1, grade IIb in 4 and grade IIa in 3 patients after surgery, according to the criteria of Shimosato. The follow-up period ranged from 13 to 64 months (mean 34). Of the 8 patients, 2 died (1 of lymph node metastasis and 1 had metastasis to a distant site), and 6 patients were alive at the last follow-up, with the longest postoperative disease-free survival being 63 months. The 5-year cumulative survival rate was 70.0%. Conclusion: These results indicate that preoperative thermochemoradiotherapy is a promising modality for patients with N[sub 3] cervical lymph node metastasis of oral cancer.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to evaluate the usefulness of magnetic resonance lymphography (MRL) with superparamagnetic iron oxide (SPIO) in sentinel lymph node (SLN) mapping of clinically N0 early oral cancer, and to conduct a comparative study of this MRL with CT lymphography (CTL). CTL and MRL were performed for SLN mapping before surgery for 20 patients with clinically N0 early oral cancer. The detection rate, number, and location of SLNs in CTL and MRL were evaluated. Furthermore, optimal scanning/imaging timing in MRL was examined. SLNs were detected by CTL in 18 (90%) patients, and the total and mean number of SLN were 35 and 1.8, respectively. All SLNs could be detected 2 min and 3.5–5 min after contrast medium injection. In all patients, SLNs were detected by MRL at 10 min after SPIO injection, and the total and mean number of SLN was 53 and 2.7, respectively. MRL at 30 min after the injection showed additional 18 secondary lymph nodes. MRL with SPIO is safe and useful imaging for the detection of SLNs in clinically N0 early oral cancer, and the optimal imaging timing is 10 min after SPIO injection. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the seven-year results of photofunctionalized implants placed in regular, complex, and cancer-related cases. This study was a prospective, single-center study. Photofunctionalization was performed immediately prior to implantation with Ultraviolet (UV) light for 15 minutes. The success rate of each patient group and the influential factors on implant failure were analyzed. Seventy implants in 16 patients were included. Four implants were left submerged (sleep). The seven-year success rate of 30 implants in regular cases and 21 implants in complex cases was 100%. The success rate of 15 implants in cancer-related cases was 22.2%, in which implants were placed in resection or reconstructed sites with or without pre- or postoperative radiation history. Implant stability quotient (ISQ) values increased at second-stage surgery by 3.2 in regular cases and by 21.9 in complex cases, while it decreased by −3.5 in cancer cases. Multivariate analysis indicated that bone quality, location, and cancer resection significantly influenced implant failure. A very reliable seven-year success rate was obtained by UV-photofunctionalized implants in regular and complex cases, even with significant site-development procedures. However, the success rate in cancer cases was significantly and remarkably lower, suggesting remaining challenges of pathophysiologically compromised conditions, such as bone resection, segmental defect, and radiation. [ABSTRACT FROM AUTHOR]

We describe use of a variable oral device for efficient measurement of oral lesions. [ABSTRACT FROM AUTHOR]