Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice.

Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of 'better-hearing ear' was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient's age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and -0.33, 95% confidence intervals [11.75-37.45] and [-0.58 to -0.09], respectively), but the CI surgery side did not (-6.76, [-14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing.

Otorhinolaryngologists/head and neck surgeons' knowledge, attitudes, and practices regarding fertility preservation in young cancer patients treated with chemotherapy: an anonymous questionnaire survey.

BACKGROUND: It is well known that chemotherapy for adolescent and young adult (AYA) patients with cancer can reduce fertility regardless of the regimen. A decline in fertility greatly affects the quality of life of cancer survivors in the AYA age group; however, few patients are thought to be receiving fertility preservation measures. METHODS: A questionnaire survey was conducted to assess the current understanding and consideration of fertility among otorhinolaryngologists/head and neck surgeons who treat AYA patients with cancer, and to inform them of the guidelines for fertility preservation. A total of 275 otorhinolaryngologists/head and neck surgeons working at our hospital in Ehime, Japan, six neighboring universities, and their affiliated facilities were included in this study. The questionnaire was mailed and requested to be returned by fax. Twenty questions were asked about respondents' years of experience as physicians, specialties, experience in medical care and chemotherapy for AYA patients with cancer, and knowledge and experience in fertility reduction measures. RESULTS: Although 58.7% of the physicians were aware that cryopreservation of eggs and sperm prior to chemotherapy was recommended, only 7 out of 40 physicians (17.5%) had referred AYA patients with cancer to an appropriate medical facility (department) after obtaining informed consent for chemotherapy. CONCLUSIONS: Although fertility preservation has been discussed at professional conferences and seminars, consideration and actions in the field of otorhinolaryngology/head and neck surgery have not been sufficient. We hope that the results of this survey will help raise awareness of fertility preservation.

PD-L1 expression in tongue squamous cell carcinoma.

PURPOSE: Immune checkpoint proteins programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important therapeutic targets for head and neck cancer. This large-scale case study aimed to analyze tongue squamous cell carcinomas (SCCs) and evaluate the correlation between PD-L1 expression and clinical prognosis. So far, this study is the largest case study on PD-L1 expression in tongue SCCs. METHODS: This is a case-control study that analyzed 121 tongue SCCs. Paraffin-embedded sections and clinical data were obtained retrospectively and immunohistochemistry with PD-L1 was performed. RESULTS: 11.6% contained ≥ 50% of PD-L1-positive cells, 57.1% of these cases had a poor prognosis with nodal metastasis. Among cases of T1/2 primary lesions with nodal metastasis, cases of high PD-L1 expression had a significantly shorter disease-free survival than cases of no PD-L1 expression (p = 0.018). The hazard ratio for high PD-L1 expression was 3.21 (95 per cent CI, 1.26-8.72) compared with no PD-L1 expression after adjusting for other factors. CONCLUSIONS: These data indicate that PD-L1 upregulation in tongue SCCs is associated with a more advanced stage and shorter disease-free survival. PD-1/PD-L1 inhibitors might hence constitute potential adjuvant therapy for tongue SCCs with PD-L1 upregulation.

MACC1 expression is an indicator of recurrence in early-stage glottic cancer.

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) has been reported to be an independent indicator of poor prognoses in some kinds of cancer due to disease metastasis or recurrence. We investigated the correlation between MACC1 expression and the prognosis of glottic cancer. METHODS: Paraffin-embedded, early-stage (I or II) glottic cancer specimens (n = 52) were immunohistochemically analyzed to explore MACC1 expression. The clinical records associated with each case were also examined. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method, and between-group RFS differences were assessed using the log-rank test. The multivariate analyses were evaluated using the Cox's proportional-hazard model. RESULTS: Patients were treated with only radiotherapy (RT) (n = 37, including 18 with T1 disease and 19 with T2 disease), or with chemoradiotherapy (CRT) (n = 15, including 1 with T1 disease and 14 with T2 disease). Eleven patients demonstrated local recurrence and two patients experienced cervical lymph node recurrence. Tumor specimens were MACC1-positive in 9 of the 13 (69.2%) patients with local or neck recurrence, and 7 of the 11 (63.6%) patients with local recurrence. The RFS rate of patients who were treated with only RT was significantly lower than that of patients who were treated with CRT (P = 0.0243). The RFS rate was significantly lower in cases with MACC1 expression than in those without MACC1 expression (P = 0.0003). Multivariate analysis revealed that MACC1 expression was an independent risk factor of local recurrence (P = 0.0016). CONCLUSION: MACC1 is an independent indicator of recurrence related to RFS in early-stage glottic cancer.

Long-term treatment with clarithromycin and carbocisteine improves lung function in chronic cough patients with chronic rhinosinusitis.

PURPOSE: Chronic cough is a common complaint. Because the pathophysiology of chronic cough is complicated, the management of chronic cough is challenging. To the best of our knowledge, no previous study has examined the effect of macrolide antibiotics in chronic cough patients with chronic rhinosinusitis. The purpose of this study is to determine the changes in lung function for chronic cough patients with chronic rhinosinusitis who are treated by clarithromycin and carbocisteine. MATERIALS AND METHODS: Thirty-two chronic cough patients with chronic rhinosinusitis were recruited. Patients using inhaled corticosteroids and/or a bronchodilator, asthmatic patients, and patients with abnormal findings on auscultation and/or chest X-ray examination were excluded from this study. The patients received low-dose clarithromycin treatment for 3 months. Both before and after the treatment, a computed tomography (CT) scan of the paranasal sinuses, lung function test, peripheral blood test, and sino-nasal outcome test (SNOT-20) were applied. RESULTS: Both the lung function and Lund-MacKay CT scores were improved by the long-duration therapy with macrolide antibiotics. The change in obstructive pulmonary function and the improvement of the CT score in each subject were significantly correlated. SNOT scores also improved after the treatment. CONCLUSIONS: The macrolide antibiotics treatment has beneficial effects on lung function in non-asthmatic chronic cough patients with normal chest X-ray findings. The improvement of chronic rhinosinusitis may have some role in the lung condition. Upper respiratory tract examination and treatment may be useful for the management of chronic cough.

Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis.

Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (FcεRI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. FcεRI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis.

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis.

BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.

Clinicopathological Features and Outcomes of Endoscopic Submucosal Dissection for Superficial Cancer of the Pharynx.

The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of superficial pharyngeal cancer, and the efficacy and safety of ESD, we retrospectively assessed 70 pharyngeal cancers in 59 patients who underwent ESD. Of these patients, 61.0% and 50.8% had a history of esophageal cancer and head and neck cancer, respectively. The median tumor size was 15 mm, and 75.7% of the lesions were located at the piriform sinus. The en bloc resection rate was 94.9%. Treatment-related adverse events occurred in 8 cases, but there was no treatment-related death. The lateral margin was positive for neoplasm in 3 lesions (4.3%) and inconclusive in 27 lesions (38.6%), but no local recurrence was observed. Cervical lymph node metastasis was observed in 6 patients, and was successfully treated by cervical lymph node dissection. The three-year overall survival rate was 91.5% (95%CI: 76.6-97.3%) and the cause-specific survival rate was 97.6% (95%CI: 84.9-99.7%). In conclusion, ESD for superficial pharyngeal cancer was safe and effective. "Resect and watch" is probably a feasible and rational strategy for treatment of patients with superficial pharyngeal cancer.

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis.

BACKGROUND: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). METHODS: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. RESULTS: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. CONCLUSIONS: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.

Role of whole saliva in the efficacy of sublingual immunotherapy in seasonal allergic rhinitis.

BACKGROUND: The development of methods to predict the clinical effectiveness of sublingual immunotherapy (SLIT) for allergic diseases is a crucial matter. We sought to determine whether whole saliva, which is the first body component that contacts allergen extracts during SLIT, is associated with the clinical effectiveness of SLIT in Japanese cedar pollinosis. METHODS: Blood monocytes or monocytic THP-1 cells were cultured in the presence or absence of either whole saliva or pure saliva with or without treatments including filtration and blockade of TLR2 and/or TLR4 signaling. IL-10 levels in the supernatants were then measured. Whole saliva-induced IL-10 production by THP-1 cells was compared between asymptomatic and disease-onset patients during peak pollen dispersal after SLIT. RESULTS: Both monocytes and THP-1 cells produced substantial amounts of IL-10 in response to whole saliva. IL-10 production was significantly reduced in response to pure saliva and 0.2 µm-filtered saliva. Simultaneous treatment with polymyxin B and TL2.1, a neutralizing antibody against TLR2, also reduced IL-10 production. IL-10 levels produced by THP-1 cells in response to whole saliva collected prior to SLIT were significantly higher in asymptomatic patients determined by symptom-medication scores than disease-onset patients following SLIT. Such differences were not seen in saliva collected 3 months after the initiation of SLIT or saliva collected during peak pollen dispersal. CONCLUSIONS: Our results provide a basis for why the sublingual route is effective and preferable in allergen immunotherapy. Saliva-induced IL-10 levels produced by THP-1 cells may be a predictive marker for clinical remission after SLIT.

[THE EXAMINATION OF IGE AND PERIPHERAL BLOOD MONONUCLEAR CELLS RESPONSES TO FLOUR EXTRACTS IN A BAKER'S RHINITIS PATIENT].

BACKGROUND: Baker's rhinitis is a kind of occupational allergic rhinitis mainly caused by intranasal exposure to wheat and/or rye flour in bakery workers. Continuous exposure to flour may induce the onset of asthma in these patients. METHOD: We experienced a case of 34-year-old male with baker's rhinitis without asthma, and investigated responses of IgE and peripheral blood mononuclear cells (PBMCs) to flour extracts used in the bakery in practice. RESULT: In the immunoblotting, the patient's IgE reacted with 18 and 30kDa molecules in the extracts of 6 flours used in the bakery. The patient's PBMC produced a substantial amount of IL-5 and IL-13 in response to these flour extracts. CONCLUSION: It is suggested that water/salt soluble components of wheat flour selectively induce type 2 cytokines production in baker's rhinitis.

Laryngeal squamous cell papilloma is highly associated with human papillomavirus.

OBJECTIVE: To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. METHODS: Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody. RESULTS: In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (<60 years) showed a higher rate of HPV infection than older patients. Among the 34 cases with laryngeal papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other. CONCLUSIONS: HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma.

Computed Tomography Findings for Diagnosing Follicular Thyroid Neoplasms.

Since no diagnostic method has been established to distinguish follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), surgery has been the only way to reach a diagnosis of follicular neoplasm. Here we investigated the computed tomography (CT) features of follicular neoplasms, toward the goal of being able to identify specific CT features allowing the preoperative differentiation of FTC from FTA. We retrospectively analyzed the cases of 205 patients who underwent preoperative CT of the neck and were histopathologically diagnosed with FTC (n=31) or FTA (n=174) after surgery between January 2002 and June 2016 at several hospitals in Japan. In each of these 205 cases, non-enhanced and contrast-enhanced CT images were obtained, and we analyzed the CT features. On univariate analysis, inhomogeneous features of tumor lesions on contrast-enhanced CT were more frequently observed in FTC than in FTA (p=0.0032). A multivariate analysis identified inhomogeneous features of tumor lesions on contrast-enhanced CT images as an independent variable indicative of FTC (p=0.0023). CT thus offers diagnostic assistance in distinguishing FTC from FTA.

Association between impaired IL-10 production following exposure to Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic rhinosinusitis.

BACKGROUND: IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). METHODS: Dispersed nasal polyp (NP) cells and uncinate tissue (UT) cells were prepared from patients with CRS with and without NP, respectively. Cells were incubated with SEB, and then the levels of IL-10 in the cell supernatants were determined. The effect of neutralizing IL-10 on SEB-induced IL-5, IL-13, IFN-γ, and IL-17A production was examined. Expression of IL-10 in NPs was also determined. RESULTS: IL-10 was expressed in infiltrating inflammatory cells in NPs. NP cells, especially non-adherent NP cells, produced substantial amounts of IL-10 in response to SEB. Although baseline production of IL-10 was significantly higher in NP cells than UT cells, the degree of IL-10 response to SEB was not significantly different between the cell types. The degree of IL-10 production was negatively correlated with the degree of eosinophilia both in tissues and peripheral blood whereas positively correlated with the 1-s forced expiratory volume/forced vital capacity ratio. Patients with severe ECRS displayed a significant decrease in IL-10 production compared with those with non-ECRS. IL-10 neutralization significantly augmented SEB-induced IL-13 and IFN-γ production by NP cells. CONCLUSIONS: Impaired IL-10 production in response to SEB in NP may exacerbate the pathophysiology of ECRS including eosinophilia and lower airway obstruction.

Diffuse large B-cell lymphoma of the lacrimal sac arising from a patient with IgG4-related disease.

A rare case of diffuse large B-cell lymphoma (DLBCL) possibly induced by IgG4-related disease is described. A 78-year-old woman was presented with a mass of the right lacrimal sac that extended to the inferior nasal meatus through the nasolacrimal duct. Pathological diagnosis was DLBCL with diffuse distribution of IgG4 + cells in the background of this lesion. The chronic inflammatory state of IgG4-related disease could have caused the development of DLBCL.

Tumor-Associated Macrophages in the Development of 4-Nitroquinoline-1-Oxide-Induced Tongue Squamous Cell Carcinoma in a Mouse Model.

OBJECTIVE: We aimed to determine the distribution of tumor-associated macrophages (TAMs) in the development of tongue squamous cell carcinoma (SCC) and to elucidate the role of TAMs in the progression of tongue SCC. METHODS: The expression of the macrophage markers nitric oxide synthase, Retnla, and mannose receptor 1 in the development of tongue SCC was longitudinally observed using real-time quantitative polymerase chain reaction. Additionally, an immunohistochemical study using an anti-mannose receptor (MR) antibody was performed. RESULTS: The numbers of both of M1 and M2 macrophages in the tongues of mice treated with 4-nitroquinoline-1-oxide (4NQO) were significantly lower compared with those of normal tongues. The cyclooxygenase-2 (COX-2) inhibitor did not prevent cancer progression and did not affect the total number of macrophages in the tongues of 4NQO-treated mice. In the immunohistochemical studies, MR staining was observed in lymphangioendothelium in the subepithelial area of the tongues. The staining intensity of the MR was significantly stronger in the 4NQO-treated mice compared with that in control mice and 4NQO-treated mice treated with the COX-2 inhibitor. CONCLUSION: TAMs may not contribute to the development of 4NQO-induced tongue SCC. MR expression is associated with the progression of 4NQO-induced tongue SCC.

IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression.

BACKGROUND: IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined. RESULTS: IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs. CONCLUSIONS: These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.

Genetic Counseling of a Hearing-impaired Patient with Multiple Genetic Mutations.

Since April 2012, genetic testing for congenital hearing loss is covered by the public health insurance in Japan. Recent (since August 2015) developments in next-generation sequencing technology have enabled the detection of 154 mutations in 19 genes. Genetic testing provides valuable information on hearing phenotype, prognosis, and prediction of associated symptoms. We report a hearing-impaired patient in whom multiple genetic mutations were detected. This patient carries two missense mutations in GJB2 (p.G45E, p.Y136X), as well as a mitochondrial mutation (7445A>G). Since the number of genes detectable by genetic testing has increased, the diagnosis of hearing loss can be made with greater accuracy. However, it is often difficult to clinically understand and interpret the genotype information, especially when multiple gene variants are detected in one patient or family. Genetic counseling plays an important part in the intervention for or follow-up of such patients. Genotypic and phenotypic information of other family members is necessary, so that both the patient and the family can understand and accept the results of genetic testing.

Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma.

The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-ß, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with those of control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2) inhibitor. Well to moderately differentiated tongue SCC was induced in all of the experimental mice. The amount of Tregs of the experimental mice was over 10 times as much as control mice at the early stage of tumor progression. COX-2 inhibitor did not prevent the progression of tongue SCC and did not reduce the total amount of Tregs. Tregs function at the early stage of the development of tongue SCC, and it may be effective to suppress Tregs at the early stage of tumor progression for the treatment and/or prevention of tongue SCC.