Utility and optimal management of planned drug holidays during lenvatinib treatment in patients with unresectable differentiated thyroid cancer: a real-world multi-center study.

PURPOSE: Lenvatinib achieves favorable therapeutic outcomes for patients with radioactive iodine therapy refractory differentiated thyroid cancer (DTC); however, its use is associated with a high incidence of adverse events. To avoid severe adverse events, planned drug holidays (PDH) have been proposed. This study aimed to evaluate treatment effects, identify prognostic factors, and investigate the usefulness of PDH in patients with unresectable DTC who received lenvatinib across the multi-institutions. METHODS: Fifty-one patients with unresectable DTC treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated, and prognostic factors were assessed. OS, PFS, and time to treatment failure (TTF) were compared between patients with and without PDH. Lenvatinib administration schedule was evaluated in PDH. RESULTS: The 3-year OS and PFS rate were 53.5% and 42.1%, respectively. Multivariate analysis revealed that presence of maximum size of lung metastasis ≥10 mm was independent prognostic factor for poorer OS and PFS, and histology other than papillary thyroid carcinoma was the independent prognostic factor for poorer PFS. Twenty-five patients (49%) treated with PDH. There were significant differences in OS, PFS, and TTF between patients with and without PDH. Various schedules were used in PDH. Eight (32%) patients required switch to the different administration schedule. CONCLUSION: Our results suggest that PDHs may extend OS, PFS, and TTF. In patients with PDH, various schedules used for lenvatinib administration highlight the difficulty in determining a uniform administration schedule. Therefore, it is crucial to consider the optimal lenvatinib administration schedule on a case-by-case basis.

Real-world treatment patterns and outcomes in Japanese patients with cervical esophageal cancer.

BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.

The impact of second-hand smoke on ear, nose, and throat diseases and head and neck cancers in Japan: a cross-sectional study using a questionnaire and secondary data from the national health and nutrition survey.

BACKGROUND: The risk of head and neck cancers (HNCs) and ear, nose, and throat (ENT) diseases due to second-hand smoke (SHS) have not been fully assessed. OBJECTIVE: To determine which ENT diseases or HNCs are associated with SHS. MATERIAL AND METHODS: Data from a survey of a cross-sectional sample of ENT patients (n = 1228) on SHS exposure were compared to control-subject data (n = 6598) from a Japan National Health Survey. Multivariate logistic regression and estimated odds ratios (ORs) determined whether SHS-disease associations were related to exposure location and disease occurrence. RESULTS: SHS was significantly associated with acute tonsillitis (OR in workplaces, 2.24 [95% CI, 1.34-3.75]; OR in restaurants, 4.24 [95% CI, 2.50-7.19]; OR in leisure places, 4.72 [95% CI, 2.93-7.62]); recurrent tonsillitis (OR in restaurants, 4.24 [95% CI, 2.52-7.13]; OR in leisure places, 5.29 [95% CI, 3.31-8.46]); facial palsy (OR in home, 2.18 [95% CI, 1.25-3.81]; OR in leisure places, 3.41 [95% CI, 1.97-5.89]); hypopharyngeal cancer (OR in home, 2.51 [95% CI, 1.18-5.36]; OR in workplaces, 2.53 [95% CI, 1.24-5.15]); and laryngeal cancer (OR in home, 2.44 [95% CI, 1.04-5.68]; OR in leisure places, 2.25 [95% CI, 1.00-5.07]). CONCLUSIONS AND SIGNIFICANCE: SHS may contribute to HNCs and ENT diseases, suggesting that merely being in the presence of smokers could increase the risk of head and neck morbidities.

Sudden sensorineural hearing loss in patients with vestibular schwannoma.

Clinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.

Thyroid lobe size predicts risk of postoperative temporary recurrent laryngeal nerve paralysis.

OBJECTIVES: In patients who had undergone thyroidectomy in Japan for benign tumor, we determined whether thyroid lobe size correlates with temporary recurrent laryngeal nerve paralysis (T-RLNP). METHODS: We retrospectively collected medical record data on usage of intraoperative neuromonitoring, laterality of thyroidectomy, amount of bleeding during surgery, duration of surgery, and whether the surgeon was a board certified otorhinolaryngologist as determined by the Oto-Rhino-Laryngological Society of Japan. Thyroid size was measured in preoperative axial computed tomography (CT) images. Receiver operating characteristic (ROC) curve analysis was used to determine the thyroid size that predicted a high risk of T-RLNP or permanent recurrent laryngeal nerve paralysis (P-RLNP). RESULTS: Of the 146 eligible patients identified, 9 (6.2%) developed T-RLNP and 2 (1.4%) developed P-RLNP. The amount of bleeding during thyroidectomy was significantly greater in T-RLNP patients than in P-RLNP patients. Thyroid sizes in CT images were significantly larger in T-RLNP patients compared to patients who did not develop RLNP (referred to hereafter as N-RLNP). ROC analysis revealed that 1.3% of thyroid lobes with an area of less than 1000.0 mm2, and 9.9% of thyroid lobes with an area of greater than 1000.0 mm2 were at risk for T-RLNP. CONCLUSION: We presented evidence that thyroid sizes, as measured on preoperative axial CT images, were larger in T-RLNP patients than in N-RLNP patients. Our results indicate a connection between benign thyroid tumor stretch injuries and T-RLNP. LEVEL OF EVIDENCE: IV.

Acquisition of resistance to androgen deprivation therapy in salivary duct carcinoma: A case report.

Salivary duct carcinoma is a relatively rare salivary cancer, and most cases are androgen receptor -positive. Salivary duct carcinoma growth is suggested to be androgen dependent, which can reportedly be controlled by androgen deprivation therapy. However, the effectiveness and underlying molecular mechanisms of androgen deprivation therapy for salivary duct carcinoma remain unknown. We report a salivary duct carcinoma case (65-year-old man) arising from the parotid gland with metastasis to the neck lymph nodes and lungs. Androgen deprivation therapy was performed according to the same protocol for prostate cancer treatment. Expression levels of androgen receptor and FOXA1 (forkhead box A1) were immunohistochemically analyzed before and after androgen deprivation therapy. Although the tumor volume was partially diminished during the first 3 months, acquired resistance to androgen deprivation therapy occurred. FOXA1 was not detected in parotid gland after androgen deprivation therapy, whereas androgen receptor expression was positive. FOXA1 expression might be related to acquired androgen deprivation therapy resistance in salivary duct carcinoma.

Utility of clinico-biological data for long-term prognosis of head and neck terminal cancer.

OBJECTIVE: The prognosis of terminal head and neck cancer is traditionally determined using indices such as the palliative prognosis index. We aimed to develop an alternative prognosis index using clinico-biological data. METHODS: This retrospective case-series study included 33 head and neck cancer patients whose cancer recurred despite receiving radiation therapy between April 2010 and April 2014. Clinico-biological data were collected the day patients were diagnosed as terminal. Bivariate correlation analyses were performed on survival times and clinico-biological data. For multivariate regression analyses, patients were divided into two groups: (1) patients who survived >120 days, and (2) those who survived <120 days. Group clinico-biological data were used to determine survival-time cutoff points for the prognosis index. RESULTS: Bivariate analyses revealed significant correlations between survival time and BMI, hemoglobin, albumin, C-reactive protein (CRP), Onodera's Prognostic Nutritional Index (O-PNI), modified Glasgow Prognostic Score (mGPS), and Performance Status (PS). Multivariate analyses showed a strong correlation between survival time and BMI. The two groups differed significantly in BMI, albumin, CRP, O-PNI, and mGPS. In multivariate analyses BMI, CRP, and O-PNI differed significantly in the two groups. CONCLUSION: BMI ≤16.4, CRP ≥1.01, and O-PNI ≤33.4 are significant predictors of long-term survival in terminal cancer patients.

Successful continual intratympanic steroid injection therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis.

OBJECTIVE: To report the treatment efficacy of continual intratympanic steroid injection (ITSI) therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis. PATIENT: A 49-year-old female diagnosed with relapsing polychondritis at the age of 45 years and who had been treated with corticosteroids and immunosuppressants developed sensorineural hearing loss in the left ear. INTERVENTION: Her unilateral hearing loss did not recover despite receiving one cyclophosphamide pulse treatment, one methylprednisolone pulse treatment, and weekly leukapheresis. Thus, we decided to initiate weekly ITSI therapy. MAIN OUTCOME MEASURE: Pure tone audiometry. RESULTS: A week after the first ITSI treatment, the patient's hearing improved. We continued ITSI therapy and attempted to extend the interval between treatments, but her hearing worsened when ITSI therapy was delivered at 2- to 3-week intervals. Thus, we returned ITSI therapy to once per week for 21 months (total of 71 treatments). She experienced no adverse events, like tympanic perforation, and 1 year after terminating the therapy, her hearing remained stable and did not worsen. CONCLUSIONS: Continual, weekly ITSI therapy was effective in treating sensorineural hearing loss accompanied by relapsing polychondritis. ITSI therapy may be a promising treatment option for sensorineural hearing loss caused by autoimmune disease.

Pretreatment Hematologic Findings as Novel Predictive Markers for Facial Palsy Prognosis.

OBJECTIVE: To examine the relationship between prognosis of 2 different facial palsies and pretreatment hematologic laboratory values. STUDY DESIGN: Multicenter case series with chart review. SETTING: Three tertiary care hospitals. SUBJECTS AND METHODS: We examined the clinical records of 468 facial palsy patients who were treated with an antiviral drug in combination with either oral or intravenous corticosteroids in participating hospitals between 2010 and 2014. Patients were divided into a Bell's palsy group or a Hunt's palsy group. We used the Yanagihara facial nerve grading system to grade the severity of facial palsy. "Recovery" from facial palsy was defined as achieving a Yanagihara score ≥36 points within 6 months of onset and having no accompanying facial contracture or synkinesis. We collected information about pretreatment hematologic findings, demographic data, and electrophysiologic test results of the Bell and Hunt group patients who recovered and those who did not. We then compared these data across the 2 palsy groups. RESULTS: In the Bell's palsy group, recovered and unrecovered patients differed significantly in age, sex, electroneuronography score, stapedial muscle reflex, neutrophil rate, lymphocyte rate, neutrophil-to-lymphocyte ratio, and initial Yanagihara score. In the Hunt's palsy group, recovered and unrecovered patients differed in age, electroneuronography score, stapedial muscle reflex, monocyte rate, platelet count, mean corpuscular volume, and initial Yanagihara score. CONCLUSIONS: Pretreatment hematologic findings, which reflect the severity of inflammation and bone marrow dysfunction caused by a virus infection, are useful for predicting the prognosis of facial palsy.

Modified endoscopic transnasal-transmaxillary-transpterygoid approach to parapharyngeal space tumor resection.

BACKGROUND: Conventional approaches for removing parapharyngeal space tumors require a cervical skin incision and resection of soft tissues between the skin and parapharyngeal space. The surgical visual field for this conventional approach is limited. METHODS: To decrease invasiveness during removal of benign parapharyngeal space tumors and to enhance the visual field, we devised a new approach called the modified endoscopic transnasal-transmaxillary-transpterygoid approach (MENMAP). The "surgical corridor" to the parapharyngeal space consists of the maxillary sinus, submucous tunnel under the lateral nasal wall, and the space created by removing the pterygoid process. RESULTS: We successfully performed en bloc removal of a parapharyngeal space tumor using the MENMAP approach. The only surgical complication was hypoesthesia of the right hard palate and maxillary gingiva, which gradually improved. CONCLUSION: The MENMAP approach is a viable alternative for removing parapharyngeal space tumors, as it is safe, feasible, and less invasive. © 2016 Wiley Periodicals, Inc. Head Neck 38: 933-938, 2016.

[Usefulness of Clinicobiological Data Obtained Prior to Cervical Lymph Node Biopsy].

INTRODUCTION: We commonly use data obtained prior to cervical lymph node biopsy for the diagnosis of malignant lymphoma. Based on such data, we can confirm whether a biopsy should be performed in some cases. Currently, the parameters used to indicate a presurgery examination prior to biopsy have been very few. So, we retrospectively analyzed cases of cervical lymph node biopsy. Moreover, we examined the usefulness of clinicobiological data obtained prior to cervical lymph node biopsy to evaluate various factors related to the diagnosis of malignant lymphoma. METHODS: This study included 77 patients for whom the initial diagnostic impression was malignant lymphoma before surgery. Of the 77 cases, 40 were diagnosed as having malignant lymphoma and 37 were diagnosed as having non-malignant lymphoma. We performed a case-controlled study to evaluate the differences in clinicobiological data between malignant and non-malignant lymphoma in terms of the following parameters: (1) age, (2) sex, (3) number of white blood cells, (4) white blood cell lymphocyte count, (5) percentage of white blood cell lymphocytes, (6) percentage of eosinophils (%), (7) percentage of monocytes (%), (8) atypical lymphocytes (%), (9) hemoglobin level, (10) lactate dehydrogenase level, (11) C-reactive protein level, (12) soluble interleukin-2 receptor (IL-2R) level, and (13) cytological findings. We used multivariate and univariate analyses to study the data statistically. RESULTS: The following 5 factors were found to be significant in a Wilcoxon t-test for malignant lymphoma: percentage of white blood cell lymphocytes, sIL-2R level, age, white blood cell lymphocyte count, and cytological findings; these factors were also significant when examined using a Pearson χ2 test. The other factors did not differ significantly between the malignant and non-malignant lymphomas. The percentage of white blood cell lymphocytes and the cytological findings were identified as significant independent factors for the diagnosis of malignant lymphoma in a multivariate analysis, whereas the other factors were not found to be significant. CONCLUSION: Based on the results of the univariate and multivariate analyses performed in the present study, the decline in the percentage of white blood cell lymphocytes and the cytological findings obtained prior to cervical lymph node biopsy are significant indicators of malignant lymphoma.

Closure of tracheoesophageal puncture with pedicled fascia flap of the sternocleidomastoid muscle.

OBJECTIVE: Closure of a tracheoesophageal puncture (TEP) formed during voice prosthesis implantation may sometimes be required. We report a new method of closure that we have termed the RESET method. METHODS: We used the RESET method for four patients. An initial incision was made at the mucocutaneous junction of the tracheostoma, and the trachea and esophagus were separated. The TEP was sectioned, and the tracheal and esophageal sides were sutured into separate layers. A pedicled fascia flap lifted from the sternocleidomastoid muscle was sandwiched between the trachea and the esophagus, and subsequently secured. RESULTS: The TEP was closed in all patients, and no complications were observed. CONCLUSION: The RESET method, using a pedicled fascia flap with stable perfusion, is a simple, reliable method of TEP closure.

Transoral closure of pharyngeal perforation caused by gastrointestinal endoscopy.

OBJECTIVE: We present a case of pharyngeal perforation caused by gastrointestinal endoscopy that was successfully repaired with transoral mucosal sutures. This is the first report of a transoral surgical closure of a perforation caused by an endoscope. We describe the repair procedure, the necessary equipment, and the effectiveness of suturing pharyngeal perforations. PATIENT: An 87-year-old woman brought to our emergency department by ambulance because of hematemesis and endoscopic hemostasis was successfully performed. But after hemostasis, CT scan showed emphysema extending from the right lower jaw to the superior mediastinum and pharyngeal perforation was observed by laryngeal fiberscope. INTERVENTION: Even though she had received conservative treatment, exacerbation of inflammation was observed and therefore we performed transoral surgery for closing the pharyngeal perforation. MAIN OUTCOME MEASURE: We followed up with CT scans, blood test and vital signs. RESULTS: The pharyngeal perforation smoothly closed and exacerbation of inflammation was not observed, even after oral ingestion began. CONCLUSION: Transoral closure of a pharyngeal perforation is less invasive and performing this procedure at an early stage can lead to a favorable outcome.

Spindle cell carcinoma of the nasal cavity.

We report an extremely rare case of spindle cell carcinoma of the sinonasal cavity. A 75-year-old man was admitted to our hospital because of right nasal obstruction. Nasal endoscopy showed a polypoid tumor measuring 3 × 3 cm at the nasal septum in the right nasal cavity, and an excisional biopsy was performed. Computed tomography (CT) demonstrated the nasal tumor extended to the maxillary sinus. Histologically, the tumor consisted of malignant spindle cells with hyperchromatic nuclei. Mitotic figures and necrosis were recognized. In some areas, edematous changes were recognized. No apparent differentiation was noted. The tumor cells were free of keratinization and intercellular bridge formations; therefore, there were no squamous cell components. Immunohistochemically, the tumor cells were positive for pancytokeratin, cytokeratin (CK)5/6, CK18, CK19, high molecular weight CK, p63, and vimentin. The tumor cells were negative for epithelial membrane antigen, CK7, CK14, p53 protein, S100 protein, HMB45, chromogranin, synaptophysin, CD34, CD56, glial fibrillary acidic protein, neuron-specific enolase, neurofilaments, α-smooth muscle actin, neuroblastoma, myoglobin, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, CD3, CD20, CD30, CD45RO, and CD45. A pathological diagnosis of spindle cell carcinoma of sinonasal lesion was made. The patient underwent resection of right maxilla followed by chemotherapy and radiation and was alive without metastasis 5 years after initial presentation.