Synthesis of the oxazolidinone fragment of thelepamide.

Thelepamide, an unique ketide-amino acid isolated from a marine annelid worm Thelepus crispus, has a unique oxazolidinone ring derived from cysteine, glycine and valine. Rareness in nature as well as promising bioactive possibility make the oxazolidinone ring an attractive synthetic target. The hydroxy oxazolidinone fragment of thelepamide was prepared by acid-catalysed N,O-acetal formation between a ketoamide and formaldehyde. Lactone-carbonyl selective isopropyl addition to an oxazilidine-dione under Grignard conditions also forms the target compound.

Isolated sphenoid sinus opacification is often asymptomatic and is not referred for otolaryngology consultation.

Isolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms "sphenoid" or "sphenoidal" using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.

Sphenopalatine artery surgery for refractory idiopathic epistaxis: Systematic review and meta-analysis.

OBJECTIVES: Epistaxis, especially posterior epistaxis, is occasionally refractory to treatment. In these cases, sphenopalatine artery surgeries, including cauterization and ligation, are required. Previous reports have demonstrated treatment results for these procedures but failed to provide high-level evidence. The aim of this study was to quantify the rates of failure and perioperative complications of these procedures by using a meta-analysis technique. METHODS: We systematically searched electronic databases and identified articles regarding epistaxis, sphenopalatine artery ligation, or cauterization. Pooled rebleeding and complication rates were calculated by using a random effects model. RESULTS: A total of 896 cases of sphenopalatine ligation or cauterization for epistaxis were analyzed. Pooled rebleeding rates for the entire cohort, cauterization group, and ligation group were 13.4% (95% confidence interval [CI] 10.0-17.8, P < 0.001), 7.2% (95% CI 4.6-11.0, P < 0.001), and 15.1% (95% CI 9.8-22.5, P < 0.001), respectively. Pooled perioperative complication rates for the entire cohort, cauterization group, and ligation group were 8.7% (95% CI 4.9-15.1, P < 0.001), 10.2% (95% CI 3.8-24.5, P < 0.001), and 6.4% (95% CI 1.8-20.9, P < 0.001), respectively. CONCLUSION: Overall, sphenopalatine surgery for refractory epistaxis is an effective method because of its low rates of failure and complications. Cauterization is more effective than ligation, whereas complications are comparable between the two procedures. Laryngoscope, 129:1731-1736, 2019.

Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: Meta-analysis.

BACKGROUND: Thrombocytosis is associated with the prognosis of various types of cancer. The purpose of this study was to quantify the prognostic impact of platelet count and platelet-lymphocyte ratio (PLR) in head and neck squamous cell carcinoma (HNSCC). METHODS: We systematically searched electronic databases and identified articles reporting an association between platelet count or PLR and HNSCC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) were extracted, and the pooled HRs were estimated using random effect models. RESULTS: Eight studies that enrolled 4096 patients and 9 studies that enrolled 2327 patients were included in the platelet count and PLR analyses, respectively. A platelet count greater than the cutoff value was associated with poor OS (HR 1.81; 95% CI 1.16-2.82) and any PLR greater than the cutoff value was associated with poor OS (HR 1.64; 95% CI 1.13-2.37). CONCLUSION: Elevated platelet count and PLR are associated with poor prognosis in patients with HNSCC.

A case of adult congenital laryngeal cleft asymptomatic until hypopharynx cancer treatment.

Laryngeal cleft is an anomaly of failed posterior closure of the larynx. Most cases are diagnosed and need treatment early in life due to respiratory and swallowing problems. We report an unusual case of a 66-year-old man with an asymptomatic laryngeal cleft until treatment for hypopharyngeal cancer. During concurrent chemoradiotherapy (CCRT), despite reduced tumor volume, he presented severe dysphagia and dyspnea, followed by severe pneumonia twice. Because CCRT had to be discontinued, a pharyngolaryngectomy was performed for the cancer treatment. The resected specimen showed total removal of the tumor and a total longitudinal cleft of the cricoid cartilage, classified as a type III laryngeal cleft by the Benjamin and Inglis' classification. A review of computed tomography images indicated that the redundant mucosa from bilateral edges closed the separation of the posterior cricoid cartilage and narrowed the laryngeal airway during CCRT. Adult presentations of laryngeal cleft are quite rare with only ten reported cases in English literature; the present case is of the oldest patient. Undiagnosed cases with laryngeal cleft may exist asymptomatically or without severe symptoms. The awareness of this condition may increase its diagnosis as a cause of diseases such as aspiration and recurrent pneumonia even in adult patients.

Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis.

BACKGROUND: Neutrophils play substantial roles in cancer progression. Previous reports demonstrated the prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in various types of solid cancers. The purpose of this study was to quantify the prognostic impact of NLR on head and neck squamous cell carcinoma (HNSCC). METHODS: We systematically searched electronic databases, identified articles regarding NLR and HNSCC mortality, and extracted hazard ratios (HRs) and 95% confidence intervals (CIs). Pooled HRs for overall survival (OS) and disease-specific survival (DSS) were estimated using random effect models. RESULTS: Nineteen studies enrolling 3770 patients were included in the analyses. Overall, NLR greater than the cutoff value was associated with poorer OS and DSS (HR 1.69; 95% CI 1.47-1.93; P < .001 and HR 1.88; 95% CI 1.20-2.95; P = .006, respectively). CONCLUSION: Elevated NLR predicts worse outcomes in patients with HNSCC.

Age-adjusted Charlson Comorbidity Index predicts prognosis of laryngopharyngeal cancer treated with radiation therapy.

OBJECTIVES: To examine the ability of comorbidity indices to predict the prognosis of laryngopharyngeal cancer and their association with treatment modalities. METHODS: This retrospective study included 198 patients with laryngeal, hypopharyngeal, and oropharyngeal cancers. The effect of comorbidity indices on overall survival between surgery and (chemo)-radiation therapy ((C)RT) groups was analyzed. The cumulative incidence rates for cancer mortality and other mortalities according to the age-adjusted Charlson Comorbidity Index (ACCI) and Charlson Comorbidity Index (CCI) were compared. RESULTS: Univariate survival analyses showed a significant association between the ACCI and overall survival in the (C)RT group, but not in the surgery group. The association between the CCI and overall survival was not significant in either group. In multivariate analyses, a high ACCI score was an independent prognostic factor in the (C)RT group (HR 2.89, 95% confidence interval (CI) 1.28-6.49), but not in the surgery group (HR 1.39, 95%CI 0.27-5.43). The higher ACCI group had increased mortality from other causes compared with the lower ACCI group (5-year cumulative incidence, 8.5% and 17.8%, respectively, p = .003). CONCLUSION: The ACCI was a better prognostic factor than the CCI. Surgery may be more beneficial than radiation for patients with a high ACCI.

Development and validation of a new comorbidity index for patients with head and neck squamous cell carcinoma in Japan.

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was an independent prognostic factor for overall survival (hazard ratio: 1.81, 95% confidence interval: 1.05-3.13; P = 0.031). The model including the OHNCI exhibited a higher prognostic capability compared to those including other commonly used comorbidity indices. The OHNCI could become the primary choice for comorbidity assessment in patients with HNSCC in Japan.

Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis.

OBJECTIVE: External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease. DATA SOURCES: PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words "external auditory canal cancer" and "temporal bone cancer." STUDY SELECTION: Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled. DATA EXTRACTION: Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted. DATA SYNTHESIS: Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis. CONCLUSION: The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC.

Prognostic role of neutrophil-lymphocyte ratio in nasopharyngeal carcinoma: A meta-analysis.

BACKGROUND: Inflammatory markers are used to predict prognosis of nasopharyngeal carcinoma (NPC). Previous reports of neutrophil-to-lymphocyte ratio (NLR) and NPC mortality are inconsistent. This study aimed to quantify the prognostic impact of NLR on NPC. METHODS: The primary outcome was overall survival (OS), and the secondary outcomes were disease-specific survival (DSS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). We systematically searched electronic databases, identified articles reporting an association between NLR and NPC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and pooled HRs for each outcome were estimated using random effect models. RESULTS: Nine studies enrolling 5397 patients were included in the analyses. NLR greater than the cutoff value was associated with poor overall survival (HR 1.51, 95% CI 1.27-1.78), disease-specific survival (HR 1.44, 95% CI 1.22-1.71), progression-free survival (HR 1.53, 95% CI 1.22-1.90), and distant metastasis-free survival (HR 1.83, 95% CI 1.14-2.95). CONCLUSIONS: Elevated NLR predicts worse OS, DSS, PFS and DMFS in patients with NPC.

Transaminase Activity Predicts Survival in Patients with Head and Neck Cancer.

Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected. The effect of the AST/ALT ratio on overall survival was analyzed using a Cox proportional hazard model. Moreover, recursive partitioning analysis (RPA) was used to divide the patients into groups on the basis of the clinical stage and AST/ALT ratio. The prognostic ability of this grouping was validated using an independent data set (N = 167). The AST/ALT ratio ranged from 0.42 to 4.30 (median, 1.42) and was a prognostic factor for overall survival that was independent of age, primary sites, and tumor stage (hazard ratio: 1.36, confidence interval: 1.08-1.68, P = 0.010). RPA divided patients with stage IVA into the following two subgroups: high AST/ALT (≥2.3) and low AST/ALT (<2.3) subgroups. The 5-year survival rate for patients with stage III, stage IVA with a low AST/ALT ratio, stage IVA with a high AST/ALT ratio, and stage IVB were 64.8%, 49.2%, 28.6%, and 33.3%, respectively (p < 0.001). Compared with the low AST/ALT group, the adjusted hazard ratio for death was 2.17 for high AST/ALT group (confidence interval: 1.02-.22 P = 0.045). The AST/ALT ratio was demonstrated to be a prognostic factor of HNSCC. The ratio subdivided patients with stage IVA into low- and high-risk groups. Moreover, intensified treatment for the high-risk group may be considered.

Health insurance status and survival among patients with head and neck cancer in Japan.

BACKGROUND: Healthcare systems vary among countries, and in many countries, insurance and economic statuses significantly impact the mortality associated with head and neck squamous cell carcinoma (HNSCC). Japan prides itself on its unique healthcare and health insurance system, which provides equal coverage and healthcare access with low individual payments to most citizens. Additionally, citizens in poverty are covered by insurance for the poor (public assistance) and receive medical and other types of assistance. Hence, they have no barriers to healthcare services. This study aimed to determine the impact of health insurance status on mortality in Japanese patients with HNSCC. METHODS: We reviewed 409 patients with HNSCC, using the Kaplan-Meier method to estimate overall survival. The association between insurance status and disease stage at diagnosis was analyzed via logistic regression. Cox and Fine-Gray proportional hazard models were employed to investigate the impact of insurance status on survival. RESULTS: The public assistance and other insurances groups did not significantly differ in clinical stage distribution. The 5-year overall survival, cumulative incidence of HNSCC death, and cumulative incidence of other death rates were 63.3 and 59.1 %, 27.0 and 31.8 %, and 10.3 and 9.7 % for the public assistance and other insurances groups, respectively. The adjusted subdistribution hazard ratio for the association between public assistance and HNSCC death was 0.73 (95 % confidence interval 0.44-1.21). CONCLUSIONS: The demonstrated non-inferiority of public assistance regarding HNSCC-specific mortality indicates the equality of healthcare in Japan, irrespective of the insurance status, and the superiority of the Japanese healthcare system.

Risk factors associated with competing mortality among patients with head and neck cancer in Japan.

Conclusions This study demonstrated a high incidence of competing mortality in patients with head and neck cancer (HNC). It identified age to be an independent prognostic factor for non-cancer mortality. These findings contribute to the appropriate treatment selection in clinical settings and study design in clinical trials. Objectives To investigate the incidences of second primary cancer (SPC) and non-cancer mortalities among patients with HNC and reveal the determinant factors for these mortalities. Methods This study reviewed the records of 334 patients with HNC between 2006-2012. The cumulative incidences of HNC, non-cancer, and SPC mortalities were estimated. A Fine and Gray regression model was used to investigate factors associated with cancer and non-cancer mortalities. Results The 5-year cumulative incidences of HNC, SPC, and non-cancer mortalities were 28.0%, 2.5%, and 6.5%, respectively. In univariate analysis, the factors associated with SPC mortality were tumor site and comorbidity, whereas those associated with non-cancer mortality were age, gender, and comorbidity. In multivariate analysis, age (sub-distribution hazard ratio = 2.59) was the independent risk factor for non-cancer mortality.