Management of elderly patients with head and neck carcinoma: analysis of outcomes for radical versus palliative treatment.

BACKGROUND: There are no universally accepted treatment recommendations for elderly patients with head and neck carcinomas. This study investigated whether radical treatment in elderly patients resulted in better survival compared with palliative treatment. METHODS: We retrospectively reviewed the medical records of 724 patients aged > 60 years who underwent treatment for primary head and neck carcinomas at Hamamatsu University Hospital. We evaluated the impact of the following: age, sex, the clinical stage, smoking history, alcohol use history, primary tumor site, performance status, and Osaka Head and Neck Comorbidity Index score on overall survival using a Cox proportional hazards model. RESULTS: The 5-year overall survival rate was significantly greater for the 646 patients initially treated with radical (curative) therapy than for the 78 patients treated with palliative therapy (p < 0.01). Patients who received palliative treatment in all age groups were more likely to die than were those in the radical treatment group, after controlling for age, sex, and clinical stage of the cancer. Information on the survival status of patients was obtained after a mean follow-up period of 46 months (range 6-205 months). CONCLUSIONS: In the absence of contraindications associated with comorbidities, radical treatment protocols should be recommended for elderly patients with head and neck carcinomas because they confer better survival.

Risk Factors and Prognostic Factors of Hearing Impairment in Neonatal Intensive Care Unit-Treated Infants.

BACKGROUND: Infants admitted to the neonatal intensive care unit (NICU) have a higher incidence of congenital hearing loss compared with the healthy newborn population. OBJECTIVES: To clarify the relationship between risk factors for hearing impairment in NICU-treated infants and deterioration of the auditory brainstem response (ABR) threshold during childhood. METHOD: We screened 1,071 high-risk infants admitted to the NICU for hearing impairment. One-hundred forty-eight infants exhibited an abnormal ABR threshold of ≥40 dB nHL. We analyzed the correlation of change in ABR threshold with risk factors for future hearing impairment. RESULTS: Among infants treated in the NICU, 148 (13.8%) exhibited an ABR threshold of ≥40 dB nHL; 107 of these 148 (72.3%) showed hearing change in the process (102 showed improvement to normal hearing level, whereas 5 showed further deterioration). Our analysis showed that the factors contributing to the elevation of ABR threshold were oxygen administration and chromosomal aberrations. CONCLUSIONS: Factors related to the elevation of ABR threshold were oxygen administration and the presence of chromosomal aberrations. Awareness of risk factors that are more likely to cause hearing loss in infants may aid in follow-up treatment of these children.

Relevance of Level IIb Neck Dissection in Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND: Cervical nodal metastasis is the most important prognostic factor in patients with head and neck cancers. Unfortunately, nodal dissection at level IIb carries a risk of damage to the spinal accessory nerve. We aimed to determine the prevalence of level IIb metastasis and the relevance of nodal dissection at level IIb in patients with head and neck squamous cell carcinomas. METHODS: During neck dissection, level IIb lymph nodes obtained from 181 patients with head and neck squamous cell carcinomas were removed, processed, and histopathologically examined. All specimens were divided into two groups according to the side (affected and unaffected sides). The number of dissected lymph nodes and prevalence of level IIb metastasis in each group were then determined and compared according to the preoperative clinical N stage (cN0 and cN+). RESULTS: The study included 158 men and 23 women with a median age of 65 years (range, 17-89 years). The prevalence of pathologically confirmed level IIb metastasis was 0% for clinically node-negative (cN0) necks on the unaffected side and 10.34% for clinically node-positive necks (cN+), with an overall prevalence of 2.4%. There was a significant association between clinically determined and pathologically confirmed node negativity at level IIb. CONCLUSION: Our findings suggest that level IIb neck dissection in patients with head and neck squamous cell carcinomas may be required only if preoperative examination reveals multilevel or level IIa metastasis or suspicious level IIb metastasis.

Trough-Shaped Audiograms Are Common in Patients with Acoustic Neuroma and Sudden Sensorineural Hearing Loss.

Acoustic neuroma sometimes presents with sudden-onset sensorineural hearing loss as a primary symptom. We investigated 848 untreated cases that included 20 cases with acoustic neuroma with sudden-onset sensorineural hearing loss and 828 cases without acoustic neuroma. Fourteen of the 20 acoustic neuroma and 90 of the 828 cases of sudden-onset sensorineural hearing loss showed a trough-shaped audiogram with the greatest amount of hearing loss in the mid-frequency range. The incidence of a trough-shaped audiogram was significantly higher in patients with acoustic neuroma than in those without (p < 0.01). This study suggests that a trough audiogram is a significant finding in patients with sudden-onset sensorineural hearing loss and indicates the presence of acoustic neuroma.

Hyperbaric Oxygen Therapy as Concurrent Treatment with Systemic Steroids for Idiopathic Sudden Sensorineural Hearing Loss: A Comparison of Three Different Steroid Treatments.

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.

Risk and prognostic factors for multiple primary carcinomas in patients with head and neck cancer.

BACKGROUND: Unexpected multiple primary carcinomas (MPCs) that develop in patients with head and neck carcinomas complicate approaches to their management. We therefore investigated the clinical factors associated with survival outcomes after the treatment of MPCs. METHODS: We performed a retrospective review of records of 1104 patients who underwent treatment for primary head and neck carcinoma at Hamamatsu University Hospital. We evaluated clinical staging, age, sex, smoking, alcohol consumption, the primary tumor site (particularly the involvement of the mucosal epithelial lining of the aerodigestive tract), and overall survival (OS) as determined by Kaplan-Meier analysis. Information on patients' survival status was obtained after a mean follow-up period of 43.8 months (range, 1-144 months). RESULTS: Among 566 patients with mucosa-associated carcinoma arising in the epithelial lining, the 5- and 10-year OS rates (68.49% and 58.96%, respectively) were significantly shorter than those of patients with mucosa non-associated carcinoma (74.22%, and 66.76%, respectively) (log-rank P = 0.0219). Older age (P = 0.016) and male sex (P < 0.001) were likely independent risk factors for developing MPCs; smoking (P < 0.001) and alcohol consumption (P < 0.001) were also significant risk factors. CONCLUSION: Mucosa-associated carcinomas arising in the epithelial lining of the aerodigestive tract in the head and neck are a significant risk factor for developing MPC and are a poor prognostic factor. Careful follow-up and more frequent examinations of the aerodigestive tracts of these patients are recommended.

Photodynamic therapy in patients with head and neck squamous cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is a minimally invasive treatment for malignant tumors. The aim of this study was to determine the efficacy of PDT in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-three patients with HNSCC were treated with porfimer sodium-mediated PDT followed by intraoperative light activation at 630 nm via fiber optic microlens delivered after 48 hours of injection. RESULTS: The complete response (CR) rate was 72.7%, while the efficacy (CR + partial response) rate was 97.0%. The rate of good local control (i.e., CR without recurrence after PDT) achieved after the initial PDT (82.6%) was significantly higher than that achieved after the second or third PDT (10%); this rate remained at 62.1% without functional disturbance and disfigurement even after excluding four previously untreated patients. The final local control rate following PDT plus additional therapies was 73.8%. CONCLUSIONS: PDT is an effective therapy to treat HNSCC, and leads to an improved quality of life in patients with residual or recurrent disease. Lasers Surg. Med. 50:420-426, 2018. © 2018 Wiley Periodicals, Inc.

The Efficacy of Touch Smear Cytology in the Diagnosis of Salivary Gland Cancers.

PURPOSE: Methods for cytologic diagnosis, such as fine-needle aspiration (FNA) and touch smear (TS) cytology, have been frequently used for malignant tumor screening; however, false-negative cases often result in misdiagnosis. The purpose of this study was to investigate the causes of false-negative cases and methods to decrease the false-negative rate in salivary gland tumor TS cytology. MATERIALS AND METHODS: In this cross-sectional study, the authors examined pathologically confirmed salivary gland tumors in 127 cases in which FNA and TS cytology were performed before the operation or open biopsy at Numazu City Hospital (Numazu, Japan) from 2002 to 2016. The authors evaluated the false-negative rates of TS and FNA cytology separately and when used in combination and other variables, such as age, gender, sensitivity, accuracy, specificity, and overall pathologic diagnosis by resection. RESULTS: The overall false-negative rate of postoperative pathologic diagnosis was lower when TS and FNA were combined (1 of 127 cases; 0.8%) compared with FNA cytology alone (10 of 127 cases; 7.9%; P = .034). Suggested causes of a false-negative FNA (or TS) result include cytologic difficulties present in certain malignancies, such as mucoepidermoid carcinoma, adenoid cystic carcinoma, and others. CONCLUSION: False-negative cases were decreased when a combination of preoperative FNA and intraoperative TS cytology was performed. TS cytology appears to be a useful method to avoid misdiagnosis in salivary gland diseases.

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden Sensorineural Hearing Loss after Failure of Systemic Steroids.

We evaluated the outcomes of and prognostic factors for idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT). A retrospective review of clinical data was performed for 167 patients with ISSNHL who failed to respond to systemic steroids and were treated by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical outcomes, the averaged 5-frequency hearing level after systemic steroids, patient age, the interval between post-steroids and pre-HBOT, vertigo as a complication, the presence of diabetes mellitus, smoking history, and hypertension. Overall, after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The overall rate of hearing improvement was higher in the study group (77/167 cases, 46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed appropriately, HBOT should be able to improve hearing in many cases unresponsive to initial therapy.

Immunohistochemical techniques for the human inner ear.

In this review, we provide a description of the recent methods used for immunohistochemical staining of the human inner ear using formalin-fixed frozen, paraffin and celloidin-embedded sections. We also show the application of these immunohistochemical methods in auditory and vestibular endorgans microdissected from the human temporal bone. We compare the advantages and disadvantages of immunohistochemistry (IHC) in the different types of embedding media. IHC in frozen and paraffin-embedded sections yields a robust immunoreactive signal. Both frozen and paraffin sections would be the best alternative in the case where celloidin-embedding technique is not available. IHC in whole endorgans yields excellent results and can be used when desiring to detect regional variations of protein expression in the sensory epithelia. One advantage of microdissection is that the tissue is processed immediately and IHC can be made within 1 week of temporal bone collection. A second advantage of microdissection is the excellent preservation of both morphology and antigenicity. Using celloidin-embedded inner ear sections, we were able to detect several antigens by IHC and immunofluorescence using antigen retrieval methods. These techniques, previously applied only in animal models, allow for the study of numerous important proteins expressed in the human temporal bone potentially opening up a new field for future human inner ear research.

Small Cell Neuroendocrine Carcinomas Arising in the Head and Neck Region.

PURPOSE: This study evaluated the clinical factors associated with outcomes of head and neck small cell neuroendocrine carcinoma (SCNEC-HN). MATERIALS AND METHODS: A retrospective review of clinical data was performed for 11 patients with SCNEC-HN treated at the Hamamatsu University Hospital (Hamamatsu, Japan). Clinical features, treatment methods, and outcomes were evaluated. The main outcome measurements were disease stage, patient age, primary tumor site, treatment procedures, and estimated survival rates. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Patients were followed for a mean of 40.0 months (range, 8 to 191 months). The 1-, 2-, and 5-year overall survival rates were 52.0, 20.8, and 10.4%, respectively. Rates did not differ significantly between the N2 and N0/1 groups, although the latter had a slightly better prognosis (P = .08). CONCLUSION: Chemoradiotherapy was a reasonable treatment for patients with SCNEC-HN. Those with N0/1 or maxillary sinus SCNEC-HN had a better prognosis than those with N2 disease or cancers at other sites, respectively. However, more aggressive treatment might not be warranted even for patients with limited disease. The outcomes continue to be suboptimal, and more effective therapies are needed because most patients had local or distant failure.

Interindividual variations in aprepitant plasma pharmacokinetics in cancer patients receiving cisplatin-based chemotherapy for the first time.

The pharmacokinetics of aprepitant, a neurokinin-1 receptor antagonist, have not been fully evaluated in clinical settings. The aim of this study was to characterize the plasma pharmacokinetics of aprepitant and reveal their influence of laboratory tests and cytochrome P450 (CYP) 3A5 gene polymorphisms in cancer patients. Forty-four Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The patients did not have gastrointestinal disease and the clinical laboratory values were within their normal reference levels. The plasma concentrations of aprepitant 24 (day 2 predose), 72, and 120 h after the first aprepitant administration were determined using LC-MS/MS. The relationships between plasma exposure to aprepitant and body weight, clinical laboratory values, age, gender, or CYP3A5*3 were investigated. The median and interquartile ranges of the 120-h area under the plasma concentration time curve (AUC)(0-120) of aprepitant were 73215 and 55518-91121 ng h/mL. The coefficient of variation value for aprepitant AUC(0-120) was 53%. The AUC(0-120) of aprepitant was correlated with the levels of total bilirubin and serum albumin, respectively (r=0.454, p<0.01 and r=0.287, p=0.06), but not with other non-genetic factors and CYP3A5 genetic variants in a univariate analysis. The AUC(0-120) of aprepitant was significantly correlated with the level of total bilirubin (adjusted R(2)=0.187, p<0.01) in a multivariate analysis. In conclusion, the plasma pharmacokinetics of aprepitant varied markedly in cancer patients receiving cisplatin-based chemotherapy for the first time and were correlated with the level of total bilirubin.

Long-term survival of a patient with primary small cell neuroendocrine carcinoma of the maxillary sinus: a case report.

Small cell neuroendocrine carcinoma (SNEC) of the paranasal sinuses is an extremely rare and distinctive tumor with aggressive clinical behavior. Moreover, SNECs originating in the head and neck region have been reported to be highly aggressive and to have a poor prognosis. This report describes a patient with a maxillary sinus SNEC who was successfully treated with induction chemotherapy using cisplatin and etoposide followed by concurrent chemoradiation therapy with cisplatin and etoposide as radiosensitizers. The patient has remained free of recurrence during 7 years of follow-up. To the authors' knowledge, this is the first case report describing long-term survival in a patient with a resolved primary SNEC of the maxilla that was successfully treated with neoadjuvant chemotherapy and concurrent chemoradiotherapy. The clinical and pathologic features of the tumor and the optimal treatment of this patient are discussed.

Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients.

PURPOSE: Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia status and clinical responses in head and neck cancer patients. METHODS: Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Plasma concentrations of total and free aprepitant and ND-AP were determined at 24 h after a 3-day aprepitant treatment. The clinical responses to aprepitant and degrees of cachexia status were assessed using a questionnaire and Glasgow Prognostic Score (GPS). RESULTS: Serum albumin level was negatively correlated with the plasma concentrations of total and free aprepitant but not ND-AP. The serum albumin level had a negative correlation with the metabolic ratio of aprepitant. The patients with GPS 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant. CONCLUSION: Cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.

[Surgical indications and approaches for parapharyngeal space tumors].

In the 20-years from 1991 to 2010, we pathologically diagnosed 24 subjects with parapharyngeal space tumors by biopsying and/or resecting of 24 tumors. Of these, 18 were benign and 6 malignant. Pleomorphic adenoma and schwannoma predominated, accounting for 7 cases each. Enhanced CT and MRI were very useful in diagnosis, judging involvement and localization, and assessing radiological and pathological tumor diagnosis. Important radiological factors are determining whether tumor origin is pre-or post-styloid, and how the tumor is enhanced in CT or MRI. We treated 15 subjects surgically, telling 9 the diagnosis, and used only biopsy or scans. It is vital in follow-up to determine long-term treatment response.

Correlations between serum cetuximab and EGFR-related markers, and skin disorders in head and neck cancer patients.

PURPOSE: Cetuximab inhibits epidermal growth factor receptor (EGFR) signaling in cancer and skin cells, thereby inducing anti-cancer effects and skin disorders. The present study aimed to evaluate the relationships between serum cetuximab and EGFR-related markers, and adverse effects in head and neck cancer patients. METHODS: Thirty-four head and neck cancer patients receiving weekly intravenous cetuximab were enrolled. Serum cetuximab levels were determined just before dosing. Blood samples for determination of serum EGFR-related markers including soluble epidermal growth factor receptor (sEGFR) and interleukin-6 (IL-6) were obtained. The severities of skin disorders, their medications, and hypomagnesemia treatment were also assessed. RESULTS: Serum levels of cetuximab and sEGFR were negatively and positively correlated with that of IL-6, respectively. The serum cetuximab level was twofold higher in the patients with a grade 2-3 skin rash than with a grade 0-1 rash. The serum cetuximab cutoff value related to severe skin rash was 71 µg/mL (sensitivity, 59%; and specificity, 94%). The use of a strong topical corticosteroid for skin rash was also associated with a higher serum cetuximab level. Serum levels of sEGFR and IL-6 had no correlations with the skin disorder severities or their medications. Hypomagnesemia treatment using intravenous magnesium sulfate was not related to serum cetuximab and EGFR-related markers. CONCLUSIONS: Head and neck cancer patients with a higher serum IL-6 level tended to have a lower serum cetuximab level. Serum cetuximab had positive correlations to skin rash severity and its medication in the study population.