Mapping naso-ocular symptom scores to EQ-5D-5L utility values in Japanese cedar pollinosis.

BACKGROUND: The total naso-ocular symptom score (TSS) is widely used as an endpoint to evaluate the severity of seasonal allergic rhinitis. However, it is not a generic preference-based measure. We sought to develop an algorithm for mapping between the TSS and health utility in Japanese cedar pollinosis (JCP). We also performed a cost-utility analysis of sublingual immunotherapy (SLIT) for JCP by using this algorithm. METHODS: Patients with JCP filled out the TSS questionnaire and EQ-5D-5L simultaneously during the pollen season in 2019 and in 2020. We estimated a direct utility mapping model by regressing responses to individual TSS questions directly onto utility. The incremental cost-effectiveness ratio (ICER) of active SLIT to a placebo was determined by examining the drug expense and the estimated quality-adjusted life year (QALY) using a dataset from a double-blind placebo-controlled clinical trial. RESULTS: A total of 238 records were included for analysis. The estimated utility decreased with increasing severity of rhinitis. Patients with comorbid asthma showed lower utility. A negative and significant correlation was seen between the TSS and utility in both 2019 and 2020. The estimated equations were: Y(utility) = -0.0161∗X(TSS) + 1.005 in non-asthmatic JCP patients. The ICER of active SLIT to the placebo was estimated to be 4,049,720 and 6,011,218 JPY/QALY in the first and second year, respectively. CONCLUSIONS: It is possible to reasonably predict utility from the total naso-ocular symptom score by using regression models. In the estimated algorithm, pre-seasonal SLIT for JCP is cost-effective.

Correction to: Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

The figure shown below is the correct version. We apologize for the mistake.

All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens. METHODS: Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirus-associated oropharyngeal carcinomas, two risk categories were classified as "p53 adverse function" and "p53 favorable function" based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher's exact test. RESULTS: Multivariate analysis identified "p53 adverse function" as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin > 6 mm, the "p53 adverse function" group demonstrated significantly higher local recurrence rate than the "p53 favorable function" group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival. CONCLUSIONS: All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.

The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis.

OBJECTIVE: Combination intranasal drugs with a corticosteroid and antihistamine are available in several countries with better effect than treatments with single agents. However, it remains unclear whether this effect is also seen in Japanese cedar pollinosis (JCP), the most prevalent seasonal allergic rhinitis in Japan. We investigated the effect of an add-on intranasal antihistamine with an intranasal corticosteroid in JCP during the pollen dispersal period. (UMIN000025508) METHODS: We performed a double-blinded, randomized, placebo-controlled trial from March 1 to 14, 2017. Patients (n = 20 per group) received either a mometasone furoate nasal spray (MFNS) plus a levocabastine nasal spray (levocabastine group) or MFNS plus a placebo nasal spray (placebo group). The primary endpoint was the difference in the total nasal symptom score (TNSS) after treatment between the two groups. Differences in the total ocular symptom score, total symptom score, total medication score, total symptom-medication score, and five individual symptoms as well as safety were the secondary endpoints. RESULTS: The change in the TNSS from baseline was significantly greater in the levocabastine group than in the placebo group. A significant reduction in the TNSS was observed more than 6 days earlier in the levocabastine group than in the placebo group. Such add-on effects were also seen in the secondary endpoints. Both treatments were well-tolerated. CONCLUSION: The intranasal antihistamine provided better control of not only nasal symptoms, but also of ocular symptoms, and decreased the need for rescue medications when added to intranasal corticosteroid treatment in JCP patients.

Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

Although iron overload is implicated in hepatocarcinogenesis, the precise mechanism was not known yet. In the present study, we investigated the effect of iron overload upon the induction of hepatocyte proliferation after 70% partial hepatectomy (PH) in rats fed with rat chow with 3% carbonyl iron for 3 months. In normal-diet rats, the increase in Ki-67 labeling index (LI) commenced at 24 h post-PH and the LIs of proliferating cell nuclear antigen (PCNA) incorporated 5-bromo-2'-deoxyuridine (BrdU) and phospho-histone H3 reached maximum values at 36 and 48 h after PH, respectively. In iron-overload rats, the above parameters occurred 12 h earlier compared to that of normal-diet rats, shortening the G0-G1 transition. Interestingly, nuclear staining for metallothionein (MT), which is essential for hepatocyte proliferation, was noted even at 0 h in iron-overload rats, while MT expression occurred at 6 h in the normal rats. Moreover, nuclear factor kappa B (NF-κB) expression, which is an essential early event leading to liver regeneration, was detected in Kupffer cells at 0 h in iron-overload rats. These results may indicate that overloaded iron, maybe through the induction of MT and NF-κB, may keep liver as a state ready to regenerate in response to PH, by bypassing signal transduction cascades involved in the initiation of liver regeneration.

Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma.

Introduction: Although patients with oral squamous cell carcinoma who develop contralateral neck metastasis (CLNM) have worse survival outcomes than those without CLNM, accurate prediction of occult CLNM in clinically negative contralateral neck (contralateral cN0) remains difficult. This study aimed to identify clinicopathological factors that could reliably predict CLNM in patients with locally advanced (clinical T3 and T4a) tongue squamous cell carcinoma (TSCC). Patients and methods: The medical data of 32 patients with cT3-4a TSCC who underwent curative surgery between 2010 and 2017 were retrospectively analyzed. The correlation of clinicopathological variables with CLNM was examined using logistic regression analysis. The diagnostic performance of significant variables was evaluated using the area under the receiver operating characteristic curves (AUC). Overall survival (OS) and disease-free survival (DFS) were assessed using a Cox proportional hazards model. Results: CLNM was eventually confirmed in 11 patients (34.4%). Multivariate logistic regression showed that midline involvement [odds ratio (OR) = 23.10, P = 0.017] and perineural invasion (PNI, OR = 14.96, P = 0.014) were independent predictors of CLNM. Notably, the prediction model comprising a combination of midline involvement and PNI exhibited superior diagnostic performance with an even higher OR of 80.00 (P < 0.001), accuracy of 90.3%, and AUC of 0.876. The multivariate Cox hazards model revealed independent significance of CLNM as an unfavorable prognostic factor for both OS [hazard ratio (HR) = 5.154, P = 0.031] and DFS (HR = 3.359, P = 0.038), as well as that of PNI for OS (HR = 5.623, P = 0.033). Conclusion: Our findings suggest that coexisting midline involvement and PNI of the primary tumor is highly predictive of CLNM development, which independently affects both OS and DFS in patients with locally advanced TSCC. Such reliable prediction enables efficient control of CLNM by optimizing management of the contralateral cN0 neck, which will likely contribute to improved prognosis of those patients without unnecessarily compromising their quality of life.

Resection of carcinoma of the external auditory canal in a patient with a high jugular bulb using temporal craniotomy.

External auditory canal (EAC) carcinoma is a rare and unusual malignancy. The complex anatomy and relationship between the tumor and surrounding tissues in a limited space render it difficult to attain safe resection margins during surgery. A high jugular bulb (HJB) is one such anatomical variation that has important surgical implications that complicate the surgical procedure for EAC carcinoma. A 73-year-old woman presented with a 3-month history of right ear pain. Pathological findings and computed tomography (CT) revealed EAC carcinoma, which was expanding to the middle ear (ME). Although there was no cavity inside the ME, an HJB was detected. Surgical treatment using a temporal incision for temporal craniotomy achieved complete resection of the tumor and preserved facial nerve function. The patient recovered without complications and was discharged 17 days after the operation. Temporal incision and temporal craniotomy is a useful approach for EAC carcinoma with HJB.