Practicality and Hemodynamic Advantage of Microvascularly Augmented Pectoralis Major Musculocutaneous Flap: Technical Approach and Evidence Based on Indocyanine Green Angiography.

ABSTRACT: We have recently shown that including the blood flow from the lateral thoracic artery (LTA) in addition to the thoracoacromial artery in the pectoralis major muscle musculocutaneous (PMMC) flap (bipedicle PMMC flap) can increase the perfusion of the flap. We also developed the concept of the supercharged PMMC flap, in which the LTA included in the flap was once cut and anastomosed to a cervical artery under a microscope. It is an effective solution to maintain the additional blood flow from the LTA, when the length of the LTA is compromised for reconstruction. The mandibular reconstruction of an oral cancer patient was performed with a supercharged PMMC flap. Intraoperative indocyanine green angiography was performed in a single pedicle, bipedicle, and supercharged conditions, and the videos were analyzed with a quantitative assessment system of perfusion using some parameters. As a result, blood supply from the LTA was essential for flap survival in this patient, and supercharging from the cervical artery improved flap perfusion compared with the perfusion in the bipedicle condition. The supercharged PMMC flap can resolve the compromise of pedicle length and be also hemodynamically advantageous, thus making the reconstruction more reliable than the conventional technique.

GPRC5B (G protein-coupled receptor class C group 5 member B) suppresses glucose starvation-induced apoptosis in head-and-neck squamous cell carcinoma.

G protein-coupled receptor class C group 5 member B (GPRC5B) is involved in extracellular glucose sensing, glucose metabolism, and insulin resistance. Many cancers require glucose at high concentrations to survive and grow. We have investigated the association between tumour GPRC5B expression and the prognosis for patients with cancer, including head-and-neck squamous cell carcinoma (HNSCC), using data from The Human Protein Atlas. The 5-year survival rate was significantly reduced in patients with HNSCC, gastric, pancreatic, colorectal, and breast cancers if their tumours exhibited high levels of GPRC5B expression. The role of GPRC5B in glucose metabolism was assessed using six HNSCC cell lines with varying levels of GPRC5B expression. High levels of GPRC5B expression were found to favour rapid cell growth. The viability of an HNSCC cell line with normal and transfected GPRC5B expression was also assessed and no differences were observed under standard culture conditions. However, under glucose-deficient culture conditions, GPRC5B-overexpressing cells exhibited increased viability and reduced apoptosis. The results highlight the association between high GPRC5B expression and poor 5-year survival rates in patients with various cancers, including HNSCC. Furthermore, we have demonstrated that GPRC5B supports cancer cell survival under glucose-depleted conditions and could be a target molecule for cancer therapy.

Reliable and safe salivary duct repositioning technique with partial transection and intraductal stenting: Technical notes.

Salivary duct repositioning is often performed after excision of malignant tumors or removal of sialoliths to maintain salivary function and minimize the risk of swelling or pain due to the obstruction of the gland. However, there is risk of intraoperative tissue damage due to traumatic manipulation, leading to stenosis; in addition, the small diameter of the duct also renders this procedure difficult. Recently, we improved our method of salivary duct repositioning as follows. In the first technique, partial transection is made on the lateral wall of the duct ligated with thread at the end. Pulling the thread provides a view of the lumen, and appropriate tension enables a reliable and non-invasive procedure without requiring the operator to grasp the edge of the duct directly. When the diameter of the duct is small, intraductal stenting, the second technique, can be combined with the former technique by probe insertion to expand the lumen. Our approach is technically easy and simple which can be accepted by any clinicians and it could also be a promising technique that can serve as a less invasive and effective treatment.

Comparison of Clinicopathological Characteristics Between the Anterior and Posterior Type of Squamous Cell Carcinoma of the Floor of the Mouth: The Anterior Type Is a Risk Factor for Multiple Primary Cancer.

BACKGROUND: Floor of the mouth (FOM) squamous cell carcinoma (SCC) accounts for approximately 10% of all oral SCCs. FOM SCC can be classified into the anterior and posterior types according to their site of origin, but few studies have compared these types. This study sought to clarify differences in clinicopathological characteristics between these two types. METHODS: A total of 1,220 patients with oral SCC were treated at our department from January 2001 to December 2015. Among these patients, 62 had FOM SCC. The FOM SCCs were classified into two groups: the anterior type and the posterior type. The anterior and posterior types were defined by the boundary connecting the spaces between the canine and the first premolar bilaterally. We retrospectively compared the sex, age, smoking and drinking history, clinical stage, treatment, histopathological diagnosis, multiple primary cancers, and outcomes of the two groups. RESULTS: Among the 62 patients, 32 had the anterior type, while 30 had the posterior type. The anterior type was found more significantly in men (p = 0.01) and individuals with a smoking history than the posterior type (p = 0.04). pN2-3 cervical lymph node metastasis was significantly more common in the anterior type than in the posterior type (p = 0.01). The median depth of invasion in the anterior type was 4 mm. Multivariate analysis showed that the anterior type was an independent risk factor for multiple primary cancer development in FOM SCC (p = 0.02). The cumulative 10-year disease-specific survival rates of the anterior and posterior types were 92.8 and 95.0%, respectively, while the overall survival rates were 65.4 and 95.0%, respectively. In the anterior type FOM SCC, a lower overall survival rate was associated with multiple primary cancers and smoking-related diseases. CONCLUSION: Smoking cessation and adequate systemic screening for multiple primary cancers are needed to improve the prognosis of FOM SCC, particularly the anterior type.

Epithelioid cell granuloma with caseating necrosis possibly caused by periapical periodontitis: a case report.

BACKGROUND: Epithelioid cell granuloma with caseating necrosis is a typical pathological finding in tuberculosis. While specific inflammation, including that related to tuberculosis, can induce caseating granuloma formation, there have been very few reports on the induction of caseating granuloma by non-specific inflammation. Chronic periapical periodontitis is usually related to bacterial biofilm formation as well as fungal or viral infection in the periapical lesion. However, it is difficult to eliminate these extraradicular pathogenic microbes by normal endodontic therapy alone, and more invasive surgical removal is almost always required. CASE PRESENTATION: Here we describe the case of a 30-year-old Japanese woman who had suffered from dull pain related to periapical periodontitis for approximately 10 years. Although the causal tooth had been previously extracted at the Department of Oral Surgery of another hospital in 2015, inflammation of the surrounding tissue had not abated. She was referred to our hospital in May 2016 and underwent surgical debridement via an intra/extraoral approach under general anesthesia. A caseating granuloma accompanied by a small amount of fungi was histopathologically confirmed in the excised specimen. Her inflammation has not been exacerbated since the operation. CONCLUSIONS: This is the first report in which non-specific inflammation is shown to induce caseating granuloma arising in the jaw. Our report also highlights the importance of sufficient root canal treatment during the first stage of the procedure.

Appropriate surgical margin for odontogenic myxoma: a review of 12 cases.

OBJECTIVE: Odontogenic myxoma (OM) is a rare benign tumor that is frequently nonencapsulated and invades the surrounding bone, resulting in a high risk of recurrence. However, the optimal surgical technique and appropriate surgical margin remains controversial. Here, we report our clinical investigation of 12 patients with OM diagnosed histopathologically. STUDY DESIGN: We retrospectively reviewed the records of 12 patients treated at our institution. Osteotomy or bone shaving with enucleation was generally performed with 5-mm bony margins from the radiologic extent of the tumor. RESULTS: One half of the cases occurred in the maxilla and the other half in the mandible. Treatment for maxillary OM was enucleation in 2 patients and maxillectomy in 4 patients. Treatment for mandibular OM was enucleation with shaving of the surrounding bone in 1 patient and segmental mandibulectomy in 5 patients. Radiographs of surgical specimen removed by segmental mandibulectomy indicated that the mean distance between the tumor and the margin was 5.4 (range 3.4-7.0) mm. Tumor recurrence was noted in 1 patient who had undergone enucleation alone. CONCLUSION: The 1-cm surgical margin for OM, as reported conventionally, might not be necessary. A prospective study is needed to determine the appropriate surgical margin for OM.

Retrospective Study on Laser Treatment of Oral Vascular Lesions Using the "Leopard Technique": The Multiple Spot Irradiation Technique with a Single-Pulsed Wave.

OBJECTIVE: This study aimed to retrospectively evaluate the efficacy and safety of laser treatment of oral vascular lesions using the multiple spot irradiation technique with a single-pulsed wave. BACKGROUND DATA: In laser therapy for vascular lesions, heat accumulation induced by excessive irradiation can cause adverse events postoperatively, including ulcer formation, resultant scarring, and severe pain. To prevent heat accumulation and side effects, we have applied a multiple pulsed spot irradiation technique, the so-called "leopard technique" (LT) to oral vascular lesions. This approach was originally proposed for laser treatment of nevi. It can avoid thermal concentration at the same spot and spare the epithelium, which promotes smooth healing. The goal of the study was to evaluate this procedure and treatment outcomes. PATIENTS AND METHODS: The subjects were 46 patients with 47 oral vascular lesions treated with the LT using a Nd:YAG laser (1064 nm), including 24 thick lesions treated using a combination of the LT and intralesional photocoagulation. RESULTS: All treatment outcomes were satisfactory without serious complications such as deep ulcer formation, scarring, bleeding, or severe swelling. CONCLUSIONS: Laser therapy with the LT is a promising less-invasive treatment for oral vascular lesions.

Neck failure after elective neck dissection in patients with oral squamous cell carcinoma.

OBJECTIVE: Analysis of the incidence and clinical relevance of neck failure after elective neck dissection (END) in patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN: A retrospective study of 188 patients with OSCC without cervical lymph node metastases was conducted; these patients had undergone END from 2005 to 2015. The most common primary tumor location was lower gingiva, followed by tongue. RESULTS: Supraomohyoid neck dissection (SOHND) was the most common procedure. Neck failure developed in 4 pathologic negative (pN[-]) and 3 pathologic positive (pN[+]) patients. The site of neck recurrence was beyond the dissected field in all cases. The site of recurrence in pN(-) patients was ipsilateral in 2 patients and contralateral in 2, whereas the site in pN(+) patients was ipsilateral in 1 patient and contralateral in 2. CONCLUSIONS: Although neck failure after END can occur, SOHND is appropriate for END for OSCC. For tongue carcinoma, level IV dissection is recommended, and for tumors close to the midline, contralateral neck dissection is also recommended.

Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles.

Despite current therapy, head and neck squamous cell carcinomas (HNSCCs) arising from various mucosal sites of the upper aero-digestive tract frequently relapse in a loco-regional manner and have a poor prognosis. Our objective was to validate an innovative mucosal route of vaccination using plasmo virus-like particles (pVLPs) in a pre-clinical orthotopic model of HNSCCs. For this purpose, we used pVLP-E7, that are plasmid DNA encoding retroviral virus-like particles carrying a truncated E7 oncoprotein from HPV-16 as antigen model, to vaccinate mice bearing pre-established TC-1 tumors implanted into the buccal mucosa. pVLP-E7 were combined with clinical grade TLR agonists (Imiquimod and CpG-ODN). In this pre-clinical orthotopic model, whose tumor microenvironment resembles to those of human HNSCCs, different mucosal vaccination routes were tested for their ability to elicit efficient immune and antitumoral responses. Results showed that mucosal intra-cheek (IC) vaccinations using pVLP-E7, comparatively to intradermic vaccinations (ID), gave rise to higher mobilization of mucosal (CD49a(+)) CD8(+) specific effector T cells in both tumor draining lymph nodes (TdLNs) and tumor microenvironment resulting in better antitumor effects and in a long-term protection against tumor rechallenge. In vivo CD8(+) depletion demonstrated that antitumoral effects were fully dependent upon the presence of CD8(+) T cells. Validation of IC mucosal vaccinations with pVLPs combined with adjuvants using a pre-clinical orthotopic model of HNSCC provides valuable pre-clinical data to rapidly envision the use of such therapeutic vaccines in patients with HNSCCs, inasmuch as vaccinal components and adjuvants can be easily obtained as clinical grade reagents.

Chronic Sclerosing Sialadenitis of the Submandibular Gland as the Initial Symptom of IgG4-Related Disease: A Case Report.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic condition accompanied by tumefactive lesions, dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis in various organs, and, frequently, elevated serum IgG4 levels. Chronic sclerosing sialadenitis (also termed Küttner's tumor) is thought to be a lesion of IgG4-RD; thus, IgG4-related sialadenitis may be the initial symptom of IgG4-RD. We herein report a 64-year-old Japanese female with IgG4-related chronic sclerosing sialadenitis of the right submandibular gland and retroperitoneal fibrosis, who subsequently developed tubulointerstitial nephritis and pancreatitis. She was referred to our Department for treatment of swelling of the right submandibular gland; preoperative imaging studies suggested a malignant tumor. We extirpated the submandibular glands bilaterally and diagnosed IgG4-related chronic sclerosing sialadenitis pathologically. Subsequently, the patient's serum IgG4 concentration increased, and lesions in the retroperitoneum, kidney, and pancreas were confirmed by imaging. Although the radiological characteristics of these lesions mimicked malignancy, steroid treatment was commenced based on the pathology of the submandibular gland and elevated serum IgG4 level. This caused the lesions to disappear, indicating that the patient had experienced IgG4-related retroperitoneal fibrosis, tubulointerstitial nephritis, and pancreatitis. No relapse was detected for 4 years 8 months after surgery. A pathological diagnosis is crucial to exclude the possibility of malignancy and to make treatment decisions when lesions are evident in other organs. In addition, periodic evaluation of the serum IgG4 concentration and imaging of the whole body are warranted in long-term follow-up.

Clinical characteristics of multiple primary carcinomas of the oral cavity.

OBJECTIVES: This study aimed to clarify the clinical characteristics of multiple primary carcinomas of the oral cavity. MATERIALS AND METHODS: We retrospectively reviewed the cases of 1015 patients who were treated during follow up for oral cancer at Tokyo Medical and Dental University between March 2001 and December 2012. We compared the clinical characteristics of 961 patients who developed single primary oral squamous cell carcinoma (SCC) during follow up and 54 patients who subsequently developed multiple primary carcinomas in the oral cavity. RESULTS: Mean age at first diagnosis was significantly higher in patients with multiple primary carcinomas than single primary carcinoma. Multiple primary carcinomas showed a female predilection, were most prevalent in the gingiva, and tended to show earlier tumor and nodal stages than single primary carcinoma. The local recurrence rate was higher for multiple primary carcinomas than single primary carcinoma, and it increased with the number of multiple primary occurrences. The disease-specific survival rate at 10 years for patients with single primary carcinoma was 85.3% and that for patients with multiple primary carcinomas was 79.6%. The cumulative incidence rate for metachronous second multiple primary carcinomas after the onset of first carcinoma at 10 years was 8.0%. The recurrence of multiple primary carcinomas did not decrease the survival rate. CONCLUSION: Differences were found in the clinical characteristics between patients with single oral SCC and those with multiple primary oral carcinomas. Early diagnosis and treatment as well as close long-term follow up are needed for patients with multiple primary oral carcinomas.

Galectin-7 as a potential predictive marker of chemo- and/or radio-therapy resistance in oral squamous cell carcinoma.

Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC.

Myoepithelioma of the Parotid Gland Presenting as a Retroauricular Cutaneous nodule: A Case Report.

We are reporting a case of recurrent myoepithelioma of the parotid gland, that emerged as a cutaneous mass. She had a retroauricular subcutaneous mass with an underlying diagnosis of a cutaneous myoepithelioma, which was excised at a hospital's Dermatology Department 2 years earlier. The tumour was observed above the platysma and it was considered as a cutaneous myoepithelioma without the parotid gland structures. She had undergone a partial parotidectomy approximately 20 years earlier. At her first visit to our department, there was no evidence of facial nerve palsy or cervical lymphadenopathy. The radiological findings showed a multinodular growing mass of the parotid gland, just beneath the retroauricular skin and a total parotidectomy was performed. It was considered that even if the cutaneous mass emerged, the relationship between the cutaneous mass and the parotid gland should be pre-surgically examined by computed tomography (CT) or Magnetic resonance image (MRI). A long-term continuous follow-up was also needed.

Multipotency of CD11bhighGr-1+ immature myeloid cells accumulating in oral squamous cell carcinoma-bearing mice.

We demonstrated the accumulation of CD11b(high)Gr-1(+) cells in a murine model of squamous cell carcinoma (SCC). Inoculation of NR-S1K cells derived from oral SCC induced a rapid and clear accumulation of CD11b(high)Gr-1(+) cells in secondary lymphoid organs as well as in peripheral blood. Phenotypic and morphological analyses revealed that these CD11b(high)Gr-1(+) cells were not lymphoid lineage cells, mature dendritic cells, macrophages, or granulocytes. Although the freshly isolated CD11b(high) cells lacked antigen-presenting capacity, they acquired a potent antigen-presenting capacity that included the induction of MHC class II after culture with GM-CSF and IL-4 in vitro. These results suggest that CD11b(high) cells that accumulate in tumor-bearing hosts are immature myeloid cells, but have considerable potential to differentiate into potent antigen-presenting cells under appropriate culture conditions. The use of in vitro differentiated CD11b(high) cells may be a potential strategy for obtaining patient-matched dendritic cells for tumor immunotherapy.

Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma.

We examined cell surface expression of five B7 costimulatory molecules (B7-H1, B7-DC, B7h, CD80 and CD86) in human oral squamous cell carcinoma (SCC) lines. Most human SCC cell lines expressed various levels of B7-H1 and B7-DC. Their expression was further upregulated by interferon (IFN)-gamma stimulation. Immunohistochemical staining revealed substantial and predominant expression of B7-H1 on human primary oral SCC. A murine SCC line, NR-S1, neither expressed B7-H1 nor B7-DC, but induced B7-H1 by IFN-gamma stimulation in culture and the inoculation in vivo. Although NR-S1 tumors grew progressively in immunocompetent syngeneic mice, the administration of blocking anti-B7-Hl or anti-PD-1 mAb significantly inhibited the tumor growth, suggesting the negative regulation of host immune responses by the PD-1:B7-H1 pathway. Our results demonstrate that B7-H1 is predominantly induced on oral SCC within the B7 family molecules. A successful inhibition of tumor growth by blockade of the PD-1:B7-H1 pathway may implicate a new approach for immunotherapy of oral SCC.