Development of an evaluation and treatment strategy for olfactory neuroblastoma: a review of evidence from large-scale studies, including population-based and multicenter studies, and meta-analyses.

Olfactory neuroblastoma is a rare sinonasal malignancy arising from the olfactory epithelium that is characterized by skull base involvement and a modest natural history. Because of its rarity and long course, identification of independent prognostic factors is dependent on multivariate analysis of large, long-term data. In this review, we outline evidence for the evaluation and treatment of olfactory neuroblastoma obtained from recent large-scale population-based studies, meta-analyses and multicenter studies. Hyams grade is currently the only pathological grade system for olfactory neuroblastoma. The modified Kadish staging and Dulguerov classification are available for clinical staging. The results of large-scale studies have confirmed Hyams, the modified Kadish and Dulguerov as independent prognostic factors. Surgery followed by radiotherapy provides the best overall survival and recurrence-free survival for resectable disease. The question of whether postoperative radiotherapy should be administered for all cases or only for those at risk of recurrence remains unanswered. Exclusively endoscopic resection is indicated for modified Kadish A/B cases without any increase in the risk of death or recurrence, and is also indicated for modified Kadish C cases if a negative surgical margin is ensured. For more advanced cases, such as those with extensive brain infiltration, the open approach is indicated. Elective nodal irradiation prevents late nodal recurrence of N0 patients. Chemotherapy has failed to show a benefit in survival or disease control. Current needs for olfactory neuroblastoma include the development and validation of refined staging systems suitable for current practice; expansion of indications for endoscopic surgery; less invasive surgery; definitive radiotherapy and novel systemic therapy.

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.

A Case of Syphilis Suspected Preoperatively as a Case of Tongue Cancer.

Syphilis is a sexually transmitted disease caused by Treponema pallidum (TP). We report a case of syphilis that was initially suspected as tongue cancer. An 86-year-old man consulted a neighborhood clinic with an approximately one-month history of pain in the right tongue. The result of scraping cytology of the tongue performed at the clinic was classified as class V, squamous cell carcinoma, and the patient was referred to our hospital. Physical examination revealed a mass on the right side of the tongue and a firm cervical mass. Biopsy revealed no evidence of malignancy; however, the imaging findings led to the suspicion of tongue cancer and lymph node metastasis. The results of blood examination revealed that the patient had syphilis, but since the patient showed few other symptoms, we decided to treat the infection after the planned surgery. We performed right partial glossectomy and neck dissection; however, the postoperative histopathology revealed no evidence of malignancy but nonspecific inflammatory changes with TP spirochetes. The incidence of syphilis has increased dramatically around the world, including Japan, during the last 20 years, and it no longer remains a rare disease. Therefore, syphilis should be included in the differential diagnosis of oral or cervical masses.

Post-intubation laryngeal injury after COVID-19 treatment causing dyspnea: A report of six cases.

Severe cases of COVID-19 often require orotracheal intubation (OTI) and mechanical ventilation, and post-intubation laryngeal injury (PI-LI) is one of the important complications of OTI. Some studies have claimed that the frequency of PI-LI may be higher in COVID-19 patients as compared with that in non-COVID-19 patients, because of the larger size of endotracheal tube used, the longer OTI time, use of prone positioning of the patients, etc. Herein, we describe six cases of PI-LI who presented with dyspnea after recovering from COVID-19. Five of the patients were male and the median OTI period was 9 days. All the patients showed abnormal endoscopic findings, including posterior glottic synechiae/stenosis or subglottic/posterior glottic granulomas. Four patients required surgical intervention, including tracheostomy, laryngomicrosurgery, or laterofixation of the vocal cord. Many post-COVID-19 patients experience persistent symptoms (post-COVID-19 syndrome), including dyspnea. Two of our patients with dyspnea had been treated by internists as cases of post-COVID-19 syndrome. Therefore, we wish to underscore the need for every healthcare professional to be aware of the possibility of PI-LI after OTI, especially during the ongoing COVID-19 pandemic. Otolaryngologists should undertake endoscopic assessment of the larynx in patients presenting with dyspnea after recovering from COVID-19.

A New Technique for the Endoscopic Reconstruction of Skull Base Defects Using Multiple-balloon Catheters.

Cerebrospinal fluid (CSF) leakage is a major complication following endoscopic endonasal skull base surgery. Various skull base reconstruction methods are available, and the use of a vascularized nasoseptal flap (NSF) in skull base reconstruction has greatly contributed to a decrease in the CSF leak rate. A balloon catheter such as a sinus balloon or a Foley catheter is often used to support an NSF; however, in cases wherein nasal and/or paranasal structures supporting the balloon are lacking following the surgery, the NSF is not properly fixed and postoperative CSF leak may occur. Here we introduce a new technique of using multiple-balloon catheters to fix an NSF in such cases and provide the results of our analysis of the new technique's efficacy. Eight patients who underwent endonasal endoscopic surgery for the following cases were included: olfactory neuroblastoma (n = 6), recurrent craniofacial meningioma (n = 1), and recurrent chordoma (n = 1). After tumor resection, multilayered reconstruction with vascularized NSF was performed. Given that the Foley catheter was not stable to fix the flap in each case, we used an additional nasal catheter to support the Foley catheter. No complications such as postoperative CSF leak and necrosis of the vascularized flap were observed. These results suggest that the multiple-balloon catheter technique is a useful method for fixing the NSF to the skull base even when nasal cavity structures are missing due to surgical removal.

PHOX2B is a Sensitive and Specific Marker for the Histopathological Diagnosis of Pheochromocytoma and Paraganglioma.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are non-epithelial neuroendocrine neoplasms originating from the adrenal medulla and paraganglion of the sympathetic and parasympathetic nervous system, respectively. PCCs and PGLs show histological similarities with other epithelial neuroendocrine neoplasms and olfactory neuroblastomas (ONBs), and the differential diagnosis of PGLs is particularly difficult. Therefore, we compared the sensitivity of PHOX2A, PHOX2B, and tyrosine hydroxylase (TH) in the histopathological diagnosis of PCCs and PGLs immunohistochemically using the tissue microarrays of 297 neoplasms including PCCs, PGLs, neuroblastomas, ganglioneuromas, epithelial neuroendocrine neoplasms, and ONBs. Using cutoff values of 25%, 5%, and 5% of tumor cells expressing PHOX2A, PHOX2B, and TH, respectively, as positive, 40 of 51 PCCs, 32 of 33 parasympathetic/head and neck PGLs (HNPGLs), 17 of 19 sympathetic/thoracoabdominal PGLs (TAPGLs), and 12 of 152 epithelial neuroendocrine neoplasms, including 123 well-differentiated and 29 poorly differentiated neuroendocrine neoplasms, were PHOX2A-positive. All 51 PCCs, 33 HNPGLs, and 19 TAPGLs were PHOX2B-positive, while all 152 epithelial neuroendocrine neoplasms were PHOX2B-negative. Moreover, 50 of 51 PCCs, 13 of 33 HNPGLs, all TAPGLs, and 12 of 152 epithelial neuroendocrine neoplasms were TH-positive. All ONBs were negative for PHOX2A, PHOX2B, and TH. PHOX2B was the most sensitive and specific diagnostic marker for PCCs and PGLs among PHOX2A, PHOX2B, and TH. PHOX2B can facilitate identification of PCCs and PGLs from epithelial neuroendocrine neoplasms and ONBs, especially in the case of HNPGLs, in which TH is often negative.

Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer.

Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the clinical utility of CGP and identified predictive biomarkers that respond to ICIs in R/M HNC. We evaluated over 1100 cases of HNC using the nationwide genetic clinical database established by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and 54 cases in an institution-based study. The C-CAT database revealed that 23% of the cases were candidates for clinical trials, and 5% received biomarker-matched therapy, including NTRK fusion. Our institution-based study showed that 9% of SCC cases and 25% of salivary gland cancer cases received targeted agents. In SCC cases, the tumor mutational burden (TMB) high (≥10 Mut/Mb) group showed long-term survival (>2 years) in response to ICI therapy, whereas the PD-L1 combined positive score showed no significant difference in progression-free survival. In multivariate analysis, CCND1 amplification was associated with a lower response to ICIs. Our results indicate that CGP may be useful in identifying prognostic biomarkers for immunotherapy in patients with HNC.

Human papillomavirus-related oropharyngeal carcinoma.

It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor-node-metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.

Systemic therapy for salivary gland malignancy: current status and future perspectives.

Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a variety of biologic behaviors. Salivary gland malignancies are known as chemo-resistant tumors, which render optimal treatment challenging. This review summarizes the role of systemic therapy for salivary gland malignancies. To date, the advantage of adding concurrent chemotherapy has remained undefined for both postoperative and inoperable locally advanced salivary gland malignancy patients undergoing radiotherapy. For recurrent/metastatic disease, local and/or systemic treatment options should be discussed in a multidisciplinary setting with consideration to both patient needs and tumor factors. For symptomatic patients or those who may compromise organ function, palliative systemic therapy can be a reasonable option based on the results of phase II studies. Platinum combination regimens as first-line therapy have been widely accepted. Personalized therapies have become established options, particularly for androgen receptor-positive, HER2-positive and NTRK fusion-positive salivary gland malignancies (i.e. androgen receptor and HER2 in salivary duct carcinoma and NTRK3 in secretory carcinoma). For patients with adenoid cystic carcinoma, multi-targeted tyrosine kinase inhibitors have also been developed. Anti-PD1 checkpoint inhibitors have shown limited activity to date. Investigation of active systemic treatments for salivary gland malignancy remains a significant unmet need. Future directions might include a more comprehensive genomic screening approach (usually next-generation sequencing-based) and combination strategies using immune checkpoint inhibitors. These are rare malignancies that require ongoing effort in the conduct of high-quality clinical trials.

Superior mediastinal paraganglioma initially suspected of being a mediastinal thyroid goiter.

Paraganglioma is a rare tumor arising from paraganglia. Few reports have described paragangliomas in the superior mediastinum. We report a case of superior mediastinal paraganglioma treated in our department. A 28-year-old woman visited our department because of suspected mediastinal tumor during a medical checkup. Contrast-enhanced CT showed a 39 × 35 × 65-mm tumor with a well-defined border extending from the lower pole of the left thyroid gland to the superior mediastinum. Laboratory tests showed no evidence of catecholamine overproduction. Mediastinal thyroid goiter was the most suspected preoperative diagnosis. We decided to perform a transcervical excision for both diagnosis and treatment. The tumor was easily detached from the lower pole of the left thyroid gland and was not continuous. The tumor capsule was brittle and bled easily. The operating time was 3 h and 11 min, and the amount of bleeding was 571 mL. The pathological diagnosis was paraganglioma. Paragangliomas are characterized by abundant blood flow and are likely to result in a high intraoperative bleeding volume. In addition, if the tumor is functional, circulatory abnormalities can occur during the perioperative period. Accurate preoperative diagnoses are important, and the possibility that paragangliomas can develop in the superior mediastinum should be considered.

Evaluation of synchronous multiple primary superficial laryngo-pharyngeal cancers that were treated by endoscopic laryngo-pharyngeal surgery.

OBJECTIVE: ndoscopic laryngopharyngeal surgery (ELPS) is a useful surgery for superficial cancers of the head and neck region, but it has not yet been well evaluated for synchronous multiple primary cancers (multiple primaries). The purpose of this study was to clarify the safety and usefulness of ELPS for patients with multiple superficial primary cancers in the head and neck region. METHODS: rom December 2009 to December 2016, 145patients with superficial head and neck cancers underwent ELPS. The patients were divided into two groups; a group consisting of patients with a single primary cancer (single primary) and another group consisting of patients with synchronous multiple primaries, and the incidences of postoperative complications and lymph node metastasis were retrospectively compared between the two groups. RESULTS: f the 145 patients, 107 had a single primary cancer and 38 had multiple primaries. There was no significant difference in the age, sex, or rate of intraepithelial cancer between the two groups. Postoperative complications included dysphagia in 6 (5.6%) patients with a single primary and 2 (5.3%) patients with multiple primaries. One patient with multiple primaries required gastrostomy because of aspiration pneumonia. In addition, the following complications were also observed. Laryngeal paralysis occurred in 2 (1.9%) patients with a single primary, and 1 (2.6%) patient with multiple primaries; tracheostomy because of postoperative bleeding in 1 (0.9%) patient with a single primary; infection occurred in 2 (5.3%) patients with multiple primaries. Postoperative lymph node metastasis was found in 7 (6.5%) patients with a single primary and 6 (15.8%) patients with multiple primaries. Lymphatic invasion of the primary cancer was noted in 3 (2.8%) patients with a single primary and 5 (13.2%) patients with multiple primaries, being significantly higher in the latter group. CONCLUSION: ELPS is also a safe surgery for patients with multiple primaries. However, the incidence of lymphatic invasion of the primary cancer was significantly higher in patients with multiple primaries.

Management of tracheostomy in COVID-19 patients: The Japanese experience.

OBJECTIVE: Involvement in the tracheostomy procedure for COVID-19 patients can lead to a feeling of fear in medical staff. To address concerns over infection, we gathered and analyzed experiences with tracheostomy in the COVID-19 patient population from all over Japan. METHODS: The data for health-care workers involved in tracheostomies for COVID-19-infected patients were gathered from academic medical centers or their affiliated hospitals from all over Japan. RESULTS: Tracheostomies have been performed in 35 COVID-19 patients with a total of 91 surgeons, 49 anesthesiologists, and 49 surgical staff members involved. Twenty-eight (80%) patients underwent surgery more than 22 days after the development of COVID-19-related symptoms (11: 22-28 days and 17: ≥29 days). Thirty (85.7%) patients underwent surgery ≥ 15 days after intubation (14: 15-21 days, 6: 22-28 days, and 10: ≥29 days). Among the total of 189 health-care workers involved in the tracheostomy procedures, 25 used a powered air-purifying respirator (PAPR) and 164 used a N95 mask and eye protection. As a result, no transmission to staff occurred during the 2 weeks of follow-up after surgery. CONCLUSION: No one involved in tracheostomy procedures were found to have been infected with COVID-19 in this Japanese study. The reason is thought to be that the timing of the surgery was quite late after the infections, and the surgery was performed using appropriate PPE and surgical procedure. The indications for and timing of tracheostomy for severe COVID-19 patients should be decided through multidisciplinary discussion.

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck.

In order to maximize the benefit of induction chemotherapy, practice based on a comprehensive interpretation of a large number of clinical trials, as in this review, is essential. The standard treatment for locally advanced squamous cell carcinoma of the head and neck is surgery or chemoradiation. However, induction chemotherapy followed by (chemo) radiotherapy may be used in some circumstances. Although many clinical trials of induction chemotherapy have been conducted, a rationale other than to preserve the larynx is still controversial. Selection of this modality should therefore be made with care. The current standard regimen for induction chemotherapy is docetaxel, cisplatin and 5-FU, but concerns remain about toxicity, cost and the duration of treatment. Regarding treatment after induction chemotherapy, it is also unclear whether radiation alone or chemoradiation is the better option. Furthermore, there is no answer as to what drugs should be used in combination with radiation therapy after induction chemotherapy. Several new induction chemotherapy treatment developments are currently underway, and future developments are expected. This review article summarizes the current position of induction chemotherapy for head and neck squamous cell carcinoma, based on the evidence produced to date, and discusses the future prospects for this treatment.

Efficacy of stress management program for depressive patients with advanced head and neck cancer: A single-center pilot study / Eficacia de un programa de control del estrés para pacientes depresivos con cáncer avanzado de cabeza y cuello: estudio de un solo centro

BACKGROUND/OBJECTIVE: Patients with head and neck cancer (HNC) have some problems such as dysfunction of breathing, eating, and/or speaking. The aim of this study was to examine efficacy of the stress management program for HNC patients (SMAP-HNC) compared with usual care (UC). METHOD: We conducted a pilot study of SMAP-HNC for depressive HNC patients between January 2016 and March 2018. The program contains psychoeducation, stress coping training, and operant reinforcement. The outcome measure was the Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy (FACT), and Brief Coping Inventory (COPE). RESULTS: Twenty patients were randomly assigned to SMAP-HNC and UC group. Although a small sample sizes, there was no significant difference of depression score change between SMAP-HNC and UC group (Hedges’d g -0.83; 95% CI -1.80 to 0.13). CONCLUSIONS: It was the first study to conduct stress management program for HNC patients. Unfortunately, our trial designed as a randomized controlled trial is underpowered to make conclusion as to the efficacy of SMAP-HNC. However, there are some valuable suggestions to modify the stress management program in future

ANTECEDENTES/OBJETIVO: Los pacientes con cáncer de cabeza y cuello (CCC) tienen algunos problemas como trastornos de la respiración, la alimentación y/o el habla. El objetivo de este estudio fue examinar la eficacia de un programa de control del estrés para pacientes con CCC (SMAP-HNC) en comparación con la atención habitual (AH). MÉTODO: Llevamos a cabo un estudio piloto de SMAP-HNC para pacientes depresivos con CCC entre enero de 2016 y marzo de 2018. El programa contiene psicoeducación, entrenamiento para afrontar el estrés y refuerzo operante. Las medidas de los resultado fueron la Hospital Anxiety and Depression Scale (HADS), la Functional Assessment of Cancer Therapy (FACT) y el Brief Coping Inventory (COPE). RESULTADOS: Veinte pacientes fueron asignados aleatoriamente al grupo SMAP-HNC y AH. Aunque los tamaños de las muestras son pequeños, no hubo diferencias significativas en el cambio en el puntaje de depresión entre el grupo SMAP-HNC y el grupo AH (g de Heges's -0,83; IC del 95%: -1,80 a 0,13). CONCLUSIONES: Es el primer estudio en emplera un programa de control del estrés para pacientes con CCC. Desafortunadamente, nuestro ensayo diseñado como un ensayo controlado aleatorio tiene poco poder para llegar a una conclusión sobre la eficacia de SMAP-HNC. Sin embargo, hay algunas sugerencias valiosas para modificar el programa de control del estrés en el futuro

Efficacy of stress management program for depressive patients with advanced head and neck cancer: A single-center pilot study.

BACKGROUND/OBJECTIVE: Patients with head and neck cancer (HNC) have some problems such as dysfunction of breathing, eating, and/or speaking. The aim of this study was to examine efficacy of the stress management program for HNC patients (SMAP-HNC) compared with usual care (UC). METHOD: We conducted a pilot study of SMAP-HNC for depressive HNC patients between January 2016 and March 2018. The program contains psychoeducation, stress coping training, and operant reinforcement. The outcome measure was the Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy (FACT), and Brief Coping Inventory (COPE). RESULTS: Twenty patients were randomly assigned to SMAP-HNC and UC group. Although a small sample sizes, there was no significant difference of depression score change between SMAP-HNC and UC group (Hedges'd g -0.83; 95% CI -1.80 to 0.13). CONCLUSIONS: It was the first study to conduct stress management program for HNC patients. Unfortunately, our trial designed as a randomized controlled trial is underpowered to make conclusion as to the efficacy of SMAP-HNC. However, there are some valuable suggestions to modify the stress management program in future.

ANTECEDENTES/OBJETIVO: Los pacientes con cáncer de cabeza y cuello (CCC) tienen algunos problemas como trastornos de la respiración, la alimentación y/o el habla. El objetivo de este estudio fue examinar la eficacia de un programa de control del estrés para pacientes con CCC (SMAP-HNC) en comparación con la atención habitual (AH). MÉTODO: Llevamos a cabo un estudio piloto de SMAP-HNC para pacientes depresivos con CCC entre enero de 2016 y marzo de 2018. El programa contiene psicoeducación, entrenamiento para afrontar el estrés y refuerzo operante. Las medidas de los resultado fueron la Hospital Anxiety and Depression Scale (HADS), la Functional Assessment of Cancer Therapy (FACT) y el Brief Coping Inventory (COPE). RESULTADOS: Veinte pacientes fueron asignados aleatoriamente al grupo SMAP-HNC y AH. Aunque los tamaños de las muestras son pequeños, no hubo diferencias significativas en el cambio en el puntaje de depresión entre el grupo SMAP-HNC y el grupo AH (g de Heges's -0,83; IC del 95%: -1,80 a 0,13). CONCLUSIONES: Es el primer estudio en emplera un programa de control del estrés para pacientes con CCC. Desafortunadamente, nuestro ensayo diseñado como un ensayo controlado aleatorio tiene poco poder para llegar a una conclusión sobre la eficacia de SMAP-HNC. Sin embargo, hay algunas sugerencias valiosas para modificar el programa de control del estrés en el futuro.

Immunotherapy for squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.

The quantitative analysis of the human papillomavirus DNA load in submandibular gland lesions with droplet digital polymerase chain reaction.

BACKGROUND: The relationship between infection with human papillomavirus (HPV) and tumorigenesis of salivary gland remains controversial. OBJECTIVES: This study explored the relationship between HPV and salivary gland lesions as well as that of the HPV infection status and p16INK4A immunoreactivity. The HPV DNA loads were also quantitatively evaluated. MATERIALS AND METHODS: Tissue samples from 31 submandibular gland lesions were evaluated. p16INK4A immunohistochemical (IHC) staining, nested polymerase chain reaction (PCR), DNA sequencing, and droplet digital PCR (ddPCR) were performed. RESULTS: Non-neoplastic lesion, benign tumors, and malignant tumors were noted in 9, 16, 6 cases, respectively. p16INK4A immunoreactivity was higher in malignant tumors than in benign tumors (50.0% vs. 6.3%). Single PCR with MY09/11 found that all samples were negative. Nevertheless, nested PCR revealed a high HPV-DNA positivity rate of 96.8%. No relationship between the HPV status and p16INK4A immunoreactivity was shown. HPV-18 was the only subtype identified in this study. ddPCR showed significantly lower HPV-18 DNA loads in submandibular gland lesions than in oropharyngeal cancers. CONCLUSIONS: HPV-DNA positivity and p16INK4A-immunoreactivity were not correlated in submandibular gland lesions. The loads of HPV DNA detected in this study were small. HPV positivity therefore may not be associated with tumorigenesis of the submandibular gland.

Pigmented villonodular synovitis occurring in the temporomandibular joint.

OBJECTIVE: Pigmented villonodular synovitis occurring in the region of the temporomandibular joint is a rare disease, requiring a review of the treatment method, follow-up period. METHOD: Refer to the past literature, along with a retrospective search. RESULTS: An excision, including the skull base bone, was performed in all cases; however, recurrence was found in one case on which fractional excision was performed. Past reports have also indicated that en bloc resection was considered desirable. CONCLUSION: It is necessary to perform en bloc resection on patients with pigmented villonodular synovitis occurring in the region of the temporomandibular joint. Furthermore, due to reported cases of recurrence after a long period of time, follow-up observations of about 10 years are considered necessary.

[Combined Anterior Craniofacial Resection for Locally Advanced Ethmoid Carcinomas].

OBJECTIVE: Carcinoma of the ethmoid sinus is very rare, and treatment for locally advanced tumors remains as a formidable challenge to the clinician. We reviewed cases of ethmoid carcinoma in which anterior craniofacial resection had been undertaken and evaluated the safety and validity of the operative methods. METHODS: We retrospectively reviewed 13 patients with ethmoid carcinoma who underwent combined anterior craniofacial resection. We evaluated the surgical procedures, complications, outcomes, local recurrence, and the survival rate. RESULTS: Coronal incision and anterior craniotomy were performed in all cases. Four out of 13 cases underwent ipsilateral orbital exenteration due to involvement of the orbital contents. There were no potentially fatal complications, except for two cases of epidural abscesses which were successfully cured. Positive surgical margins were observed in 6 patients, and they received postoperative radiotherapy and/or chemotherapy. Local recurrences occurred in 4 cases, and 3 died at 9, 11, and 49 months after the surgery. Distant metastasis was not observed during the observation period. The overall 5-year survival rate was 75.2% (Kaplan-Meier method). CONCLUSION: These tumors were safely removed without severe complications and postoperative mortality. Combined anterior craniofacial resection is an effective and safe option for treatment of locally advanced ethmoid carcinomas after various preoperative treatments.

Clinical prognostic factors for tinnitus retraining therapy with a sound generator in tinnitus patients.

OBJECTIVES: The purpose of the present study is to find out the clinical characteristics which determine candidates for tinnitus retraining therapy (TRT) with a sound generator (SG) as well as the prognosis of this treatment. METHOD: This study enrolled 270 serious tinnitus patients who visited this institute between January 2004 and December 2008 in the TRT program. The relationships among compliance, efficacy, clinical characteristics, and affinity for SG were evaluated retrospectively. RESULTS: The persistence rate at one month was 61.5%. The shorter duration and higher pitch of tinnitus were significant independent predictors of compliance. Six months after the initiation of TRT, 65.2% subjects demonstrated significant relief from tinnitus. The Kaplan-Meier method demonstrated that the overall efficacy rate at 18 months was 86.5%. The lower loudness of tinnitus, recognition of tinnitus attenuation by a sound generator, and patient's positive attitude toward TRT were significant variables for predicting favorable results. CONCLUSION: The patients with lower loudness of tinnitus were suitable for TRT with a SG.