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The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear.We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed.The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors.Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Background The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS). Methods We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status. Results The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p Conclusions TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.

Palonosetron, a long-acting 5-HT3 receptor antagonist, is an effective antiemetic agent for chemotherapy-induced nausea and vomiting; however, it sometimes causes severe constipation. The aim of the present study was to evaluate the severity of palonosetron-related constipation. We retrospectively analyzed the incidence and severity of constipation after intravenous administration of 0.75-mg palonosetron in 150 chemotherapy-naive patients who received first-line chemotherapy at Saga University Hospital. Constipation was classified into grades 1–5 according to the Common Terminology Criteria for Adverse Events version 5.0. Multiple logistic regression analysis was performed to identify factors associated with palonosetron-related worsening of constipation to grade 2 or higher. Palonosetron significantly increased the incidence and severity of constipation (incidence: before vs. after palonosetron, 35.4% vs. 74.0%, p < 0.0001, and severity: before vs. after palonosetron, 26.7% and 8.7% in grades 1 and 2, respectively, vs. 46.7%, 23.3%, and 4.0% in grades 1, 2, and 3, respectively, p < 0.0001). Despite the use of laxatives, 4.0% of patients had grade 3 constipation requiring manual evacuation. Combination treatment with aprepitant (odds ratio (OR), 10.9; 95% confidence interval (CI), 1.3–90.0; p = 0.026) and older age (OR, 1.25; 95% CI, 1.01–1.57; p = 0.039) were factors associated with the severity of constipation. Constipation was more severe in patients receiving combination treatment with aprepitant than in those treated with palonosetron alone. Older age was also associated with increased risk of severe palonosetron-related constipation. Identification of risk factors can help target risk-based laxative therapy.

Although comprehensive gene analyses of pancreatic cancer provide new knowledge on molecular mechanisms, the usefulness and possibility of the analyses in routinely available clinical samples remain unclear. We assessed the possibility and utility of target sequencing of endoscopically obtained pancreatic cancer samples. Fifty‐eight pancreatic cancer patients who underwent EUS‐FNA or endoscopic biopsy were enrolled. The extracted DNA quantity was assessed and used for next‐generation sequencing (NGS) of 50 cancer‐related genes from which gene mutations, copy number alterations, and microsatellite instability (MSI) were extracted via secondary analysis. A median of 19.2 ng (3.8–228) of DNA was extracted from formalin‐fixed paraffin‐embedded samples. Gene alterations were detected in 55 of 58 samples (94.8%), including all samples with a DNA concentration below the detection limit (n = 11). Four frequently altered genes were KRAS (83%), TP53 (66%), SMAD4 (26%), and PTEN (17%), and molecular targetable genes were detected in 13 cases (22.4%). Five samples (8.6%) had many mutations and suspected MSI with impaired mismatch repair genes. A Cox regression analysis revealed that metastasis (p 5 ng/ml (p = 0.01, HR 2.86), ≤10 detected hotspot mutations (p = 0.03, HR 9.86), and intact Ras signaling (p, We performed next‐generation sequencing of endoscopically obtained formalin‐fixed paraffin‐embedded tissue samples from actual clinical samples of patients with pancreatic cancer to evaluate gene alterations and potential prognostic indicators. This targeted sequencing of cancer‐related genes was informative for predicting prognosis and selecting therapy.

Routinely available clinical samples of all stages of pancreatic cancer are used in the present study to elucidate its molecular mechanisms and identify novel therapeutic targets. We evaluated the use of next-generation sequencing (NGS) of endoscopically obtained pancreatic cancer tissues. We enrolled 147 patients who underwent endoscopic ultrasound-guided fine-needle aspiration or endoscopic biopsy. The quantity and quality of the extracted DNA was assessed. Tissue samples were used for NGS of 78 cancer-related genes, from which gene alterations and microsatellite instability (MSI) were extracted. NGS was successful in 141 out of 147 (96%) cases. Gene alterations were detected in 134 out of 141 (91%) samples, among which eight out of 10 samples with a DNA concentration below the detection limit had some type of gene alteration. Targetable genes were detected in 28 (19.9%) cases. MSI and germline mutations in homologous recombination repair associated genes were detected in 5% and 3% of cases, respectively. Cox regression analysis revealed that metastasis (P .005; hazard ratio [HR], 3.30) was associated with poor prognosis in all pancreatic cancer patients. In addition, fewer than three mutations (P = .03; HR, 2.48) and serum carcinoembryonic antigen levels5 ng/mL (P .005; HR, 3.94) were associated with worse prognosis in cases without and with metastasis, respectively. Targeted sequencing of all stages of pancreatic cancer using available samples from real clinical practice could be used to determine the relationship between gene alterations and prognosis to help determine treatment choices.

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.

Background The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established. Methods We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters. Results Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013). Conclusions Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.

Background Eosinophilic chronic rhinosinusitis (ECRS) is often complicated by asthma and can be difficult to diagnose. This study aimed to clarify the usefulness of the self-administered odor questionnaire (SAOQ) and visual analog scale (VAS) to identify olfactory disorders in patients with asthma. Methods This retrospective study was conducted on patients with asthma who were referred to the Otolaryngology clinic between May and September 2018. The treatment step of asthma, asthma control test (ACT), pulmonary function test, peripheral blood eosinophils, and fractional exhaled nitric oxide (FeNO) were analyzed. ECRS was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study score. Olfactory dysfunction was evaluated using the SAOQ and VAS for olfactory disorders. Results The study included 56 patients (18 males and 38 females), who were divided into two groups; those with ECRS (n = 18) and those without ECRS (n = 38). Age, sex, treatment step, ACT score, and pulmonary function were not significantly different between the groups. The ECRS group had a significantly higher FeNO value (89.1 ppb vs. 39.1 ppb) and a significantly lower SAOQ score (40.1% vs. 96.1%). The area under the receiver operating characteristic curve for the efficacy of ECRS diagnosis was 0.88, 0.889, 0.799, and 0.757 for SAOQ, VAS, blood eosinophil count, and FeNO, respectively. Conclusion The SAOQ and VAS scores were useful tools that presented similar results to the blood eosinophil count and FeNO, and may help to improve the diagnosis of ECRS in patients with asthma.

Objective In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases. Methods An experimental rat model of chronic acid reflux esophagitis was surgically created. The oral cavities were observed histologically every 2 weeks until 20 weeks after surgery. Results At 10 weeks after surgery, molar crown heights in GERD rats were shorter than that in control rats, and inflammatory cell infiltration by gastric acid reflux was found in the periodontal mucosa of GERD rats. Furthermore, dental erosion progressed in GERD rats at 20 weeks after surgery, and enamel erosion and dentin exposure were observed. During the same period, inflammatory cell infiltration was observed in the mucosa of the posterior part of the tongue. These findings suggest that gastric acid reflux may be one of the exacerbating factors of dental erosion, periodontitis and glossitis. Conclusion We investigated oral changes in an experimental rat model of GERD and observed development of dental erosion, periodontitis and glossitis. Our findings suggested chronic gastric acid reflux may be involved in the pathogenesis of oral disease.

Liver damage presented as alanine aminotransferase (ALT) elevation and high ALT-caused treatment discontinuation occurs with high frequency in Japanese patients receiving daclatasvir plus asunaprevir (DCV/ASV) therapy for hepatitis C virus (HCV) infection, and its mechanism is unknown. A total of 247 Japanese patients consisting of two independent cohorts with genotype-1b HCV infection receiving DCV/ASV therapy were included. The association of ALT levels during therapy and single nucleotide polymorphisms (SNP) of five drug-metabolizing enzyme loci selected for their possible influence on NS3/4A and NS5A inhibitors was investigated. Among five SNPs, we found a significant correlation between the presence of the UGT1A1 rs4148323 A allele and ALT elevation (Grade 3 elevation in AA 57%, AG 18%, and GG 4%, P = 8.4E − 06) and drug discontinuation (AA 22%, AG 11%, and GG 2.5%, P = 8.7E − 04), while no association was observed with ALT values at baseline (Grade 3 elevation AA 0%, AG 4%, and GG 2%, P = 0.5). In contrast, patients with risk A allele for drug-induced ALT elevation had a tendency to respond more favorably to treatment (AA 100%, AG 93%, and GG 90%, P = 0.29). Through the analysis we suggest that the A allele in UGT1A1 rs4148323 (UGT1A1*6), which is highly prevalent in the Japanese population, should be considered a risk for the development of DCV/ASV therapy-induced ALT elevation. Pretreatment SNP testing of UGT1A1*6 might be beneficial for the prediction of liver damage induced by DCV/ASV or even by DCV/ASV plus beclabuvir.

Our hospital is the designated treatment base for intractable neurological diseases in the Kumamoto Prefecture. It is located in the center of the prefecture where the major 7.3-magnitude Kumamoto earthquake was recorded in 2016. In order to examine whether this earthquake affected the clinical symptoms of patients with Parkinson's disease in this hospital, we investigated outpatients examined up to 4 weeks after the earthquake. The subjects were 26 consecutive patients without any changes in anti-Parkinson's disease treatment or their attending physician during the examination period. All of the items in Part III of the Unified Parkinson's Disease Rating Scale (UPDRS), which is a clinician-scored scale for monitoring and evaluating motor function, were confirmed with the subjects before and after the earthquakes. After the earthquakes, worsened symptoms were found in 7 patients and 7 patients felt better. On the UPDRS, worsened symptoms were most commonly found among the items examining "muscle rigidity" and "slowness of movement and decreased movement" among the 7 patients with exacerbated symptoms. After the earthquake, clinical symptoms worsened significantly in women (P = 0.0188), patients with mild symptoms (P = 0.0111), and those who suffered a high degree of personal loss, such as those whose homes were damaged, who were forced to take refuge, or who had to sleep in their car (P = 0.0184). The mental and emotional burden due to the earthquake might be particularly high in the group of patients with worsened symptoms, suggestive of a relationship between stress and the exacerbation of parkinsonian symptoms.

Curiosity is often portrayed as a desirable feature of human faculty. However, curiosity may come at a cost that sometimes puts people in a harmful situation. Here, with a set of behavioural and neuroimaging experiments using stimuli that strongly trigger curiosity (e.g., magic tricks), we examined the psychological and neural mechanisms underlying the motivational effect of curiosity. We consistently demonstrated that across different samples, people were indeed willing to gamble, subjecting themselves to physical risks (i.e. electric shocks) in order to satisfy their curiosity for trivial knowledge that carries no apparent instrumental value. Also, this influence of curiosity shares common neural mechanisms with that of extrinsic incentives (i.e. hunger for food). In particular, we showed that acceptance (compared to rejection) of curiosity/incentive-driven gambles was accompanied by enhanced activity in the ventral striatum (when curiosity was elicited), which extended into the dorsal striatum (when participants made a decision).

Background: Mammary analogue secretory carcinoma (MASC) of the salivary gland shows morphologic similarities and shares an immunophenotype and characteristic ETV6-NTRK3 translocation with secretory carcinoma of the breast. We present a buccal case of MASC along with a survey-based debate about its cytologic diagnosis by fine-needle aspiration (FNA). Case: FNA of the buccal nodule of a 58-year-old Japanese man was initially performed by 3 cytologists who gave different assessments of the Papanicolaou classification (i.e., class II, III, and V). To investigate the potential for discrepant diagnosis of MASC on a larger scale, we distributed a survey with questions about the cytological diagnosis of the present case to cytologists at other institutions. A total of 109 cytologists completed the survey, providing varying assessments of the Papanicolaou classification: class I/II (14%), class III (53%), and class IV/V (33%). Most of the respondents (72%) could not identify a particular tumor or disease. Even the respondents who identified a particular tumor suggested widely differing diagnoses, from a benign lesion to various malignant tumors. Only 2 respondents correctly identified MASC. Conclusion: Our experience and the results of the survey suggest difficulty in the cytodiagnosis of MASC.

Objective To elucidate the association between gastric acid reflux and respiratory diseases by studying the histological changes of the lower airway in rats with chronic acid reflux esophagitis. Methods An experimental rat model of chronic acid reflux esophagitis was surgically created. The lower airways of these rats were histologically observed for more than 50 weeks. Results Although there were no histological changes which induced gastric acid reflux at 10 weeks after surgery, thickening of the basal laminae and the proliferation of the collagenous fibers were observed in the alveolar epithelium at 20 weeks after surgery. At 50 weeks after surgery, the collagenous fibers obliterated the pulmonary alveoli and bronchial lumen. These findings observed in the GERD rats are similar to the pathological findings of human pulmonary fibrosis. Conclusion In this study, we reported pathological changes in the lower airways of GERD rat models observed for more than 50 weeks. These results suggest that gastric acid reflux may be one of the pathogenic or exacerbating factors of pulmonary fibrosis.

BACKGROUND Lifestyle determinants of depressive state and a feeling of unhappiness in daily life were evaluated among the workers in Japan by adjusting obesity and age. METHODS A total of 3630 men aged 34 to 60 years from a workplace in Japan participated in this cross-sectional study conducted in 2006. The prevalence of depressive state and a feeling of unhappiness were evaluated by a questionnaire with questions pertaining to the age, body mass index, and six lifestyle factors. The six lifestyle factors were frequency of exercise and alcohol intake per week, smoking habit, hours of sleep per day, and frequency of eating breakfast and snack per week. The associations between depressive state and/or a feeling of unhappiness and the lifestyle factors were tested by logistic regression analysis. RESULTS The prevalence of depressive state and a feeling of unhappiness among the workers was 8.1% and 20.3%, respectively. The prevalence of workers who sleep at least for 6 hours on average, exercise regularly and eat breakfast everyday increased as the age of the workers increased. Depressive state and a feeling of unhappiness were significantly associated with age and a reduced duration of sleep even after adjustment for the other variables. No significant associations were found between the other lifestyle factors examined and depressive state and/or a feeling of unhappiness. CONCLUSIONS Depressive state and/or a feeling of unhappiness were significantly associated with a reduced duration of sleep among the workers. Aging was a preventative factor of depressive state and/or a feeling of unhappiness. The effect of obesity was adjusted in this study, but the cause-effect relation between lifestyles and depressive state and/or a feeling of unhappiness should be clarified by the follow-up study.

Devaluation-by-inhibition hypothesis demonstrated that previously ignored items are judged more negatively than previously attended and novel items. Based on this view, the present study investigated the evaluation of preceding stimuli that presumably elicit attentional processes to task-relevant stimuli. Accordingly, we employed a Posner-type cueing task followed by evaluation of the preceding cues indicating left and right directions. The important manipulation is predictability of two different preceding cues which predict the target location with high or with low probability. In Experiment 1 with two different arrows, a low predictive arrow was judged more negatively than a high predictive cue. Experiment 2 using gaze cues of two persons instead of two different arrows supported the findings of Experiment 1. These findings are consistent with devaluation-by-inhibition, suggesting that cue items triggering attention to the target are devaluated when they have less predictability.

Objective Adenoid cystic carcinoma (ACC) of the head and neck grows slowly with structural differentiation, however, this tumor nevertheless also shows a highly invasive potential and a high recurrence rate. Extracellular matrices have been suggested to play an important role in the differentiation and growth of ACC. The aim of this study is to understand the roles of laminin 5 basement membrane (BM) components, including collagen IV and laminin γ2 for the high degree of invasiveness and the recurrence of ACC. Methods Collagen IV and laminin γ2 were immunohistochemically localized in tissue sections from nine patients with ACCs. Results Cribriform structures with pseudocysts were preserved in small invading tumor nests, and the expression of both of collagen IV and laminin γ2 was observed in the inner border of the pseudocysts and the surrounding area of the tumor nests. In areas of perineural invasion, the BM components continued to be expressed around the long tumor nests. Recurrent tumors consisted of multiple small nests with a few tumor cell layers, and the expression of the BM components was observed on both the inside of the inner tumor cells and the outside of the outer tumor cells, which was an obviously different appearance from that of the primary tumor. Conclusion ACC appears to possibly grow and invade using the laminin 5 BM matrices while also preserving their differentiated architecture. The laminin 5 BM matrices might play an important role not only in the differentiation and growth, but also in the invasion and recurrence of ACC of the head and neck.

Purpose To assess the efficacy of neck dissection (ND) without glossectomy (GL) for late nodal metastases without local recurrence after brachytherapy for N0 tongue cancer. Materials and methods Among 396 patients with N0 tongue cancer treated with brachytherapy, a retrospective analysis was performed in 111 patients who were clinically diagnosed as having nodal metastases without local recurrence and whose neck lymph nodes turned out to be pathologically positive after salvage surgery. One hundred and five patients had undergone only ND (the ND group), six patients had undergone ND with GL (the ND+GL group). Results The 5 year disease-free and cause-specific survival rates after salvage therapy for the 111 patients included in this study were 58.1 and 61.9%, respectively. In the ND group, there were only nine patients who had local recurrence after ND. In addition, only six patients (5.7%) had a local recurrence within 2 years in the ND group. Sixty-three patients were free of disease after ND, 31 patients had regional or distant metastases without local recurrence and two patients had progressive disease at ND. In the ND+GL group, four patients were alive without disease and two died from regional or distant metastases. None of the patients in the ND+GL group were found to have malignant tissue in the pathological findings from the excised tongue. Conclusion GL should be avoided or suspended when the clinical evaluation had revealed cervical failure without apparent local recurrence in the mobile tongue cancer patients after initial brachytherapy.

Studies have reported the presence of relationships between the Myc target gene Mina53 and poor prognostic factors in several cancers including esophageal cancer. In this study, we investigated the relationships between Mina53 expression in gingival squamous cell carcinoma and clinicopathological factors. Seven samples of normal and dysplastic gingival tissues and 15 samples of gingival squamous cell carcinoma were immunostained for Mina53 and Ki67, and examined for the relationships between their expression and differentiation degree, lymph node metastasis, stage, tumor diameter, and prognosis. In normal and dysplastic gingival tissues, the localization of the expression of Mina53 and Ki67 was similar, but that in gingival squamous cell carcinoma tissue varied depending on the degree of differentiation. In well-differentiated GSCC with pearl formation, Mina53 was negative at the center of the clearly keratinized cancer nest, but positive in the nuclei of cells in the periphery and adjacent area of the cancer nest. In diffusely proliferating undifferentiated and moderately-differentiated GSCC showing no pearl formation, both Mina53 tended to be positive in the nuclei of cancer cells in the entire cancer nest. A significant correlation was found between the expression of Mina53 and that of Ki67 in patients with gingival squamous cell carcinoma or dysplastic gingiva. No significant correlation was noted between the expression of Mina53 or Ki67 and prognostic factors such as the degree of differentiation, lymph node metastasis, stage, and tumor diameter. In gingival squamous cell carcinoma, Mina53 expression was correlated with the proliferation of tumor cells, but unlike esophageal and other squamous cell carcinomas, not with the prognosis. The absence of correlations with prognostic factors suggests that may differ gingival squamous cell carcinoma differs biologically from esophageal squamous cell carcinoma which is correlated with Mina53 in terms of the biological expression of Mina53.

The intravenous olfaction test using prosultiamine (PST) solution is simple to perform and has been used clinically in Japan. We monitored intranasal intensity of smell continuously in real time under various conditions of administration using metal oxide semiconductor odor sensors and established an optimal PST injection procedure. In this study, we found that 1) although there was fluctuation in the pattern of intensity of increase in smell in the PST original solution test, the pattern of increase in intranasal smell intensity could be stabilized by prolonging the injection time to 40 s and 2) dilution of PST with physiological saline was effective in preventing angialgia during intravenous injection. It appears that PST administration is best performed by adding 10 ml of saline to 10 mg (2 ml) of PST and injecting the resulting 12-ml solution (6x dilution) and that the best respiratory cycle for testing is once in every 2 s.

Third-stage larvae of Gongylonema pulchrum from naturally infected dung beetles were inoculated orally into 24 rabbits. Worm recovery ranged from 54 to 91% (mean = 67.5%) during the period from 24 hr to 52 wk postinoculation (PI). Two hours PI, the larvae entered the mucosa at the junction of the stomach and esophagus and migrated upward. Early development occurred primarily in pharyngeal mucosa, tongue, and buccal mucosa. The third molt took place 11 days PI and the final molt at 36 days PI. Male worms reached sexual maturity at 7 wk PI and females at 9 wk PI. Adult worms were found mainly in the esophagus but also occurred in the tongue and the wall of the oral cavity after 30 wk PI. Embryonated eggs appeared in the feces of 3 rabbits inoculated with 50 or 100 larvae on days 72-81 PI. Morphologically, the cuticle in young fourth-stage larvae exhibited bosses on the anterior portion on day 11 PI, and the left spicule length : total body length exhibited no remarkable change between 9 and 52 wk PI. The latter finding confirms the utility of the ratio for identification of the nematode.

Purpose: Early squamous cell carcinoma of the hypopharynx is a rare clinical entity. Our objective was to analyze the outcome of patients with early hypopharyngeal cancer treated with curative radiotherapy or the combination of preoperative radiotherapy with surgery. Methods and Materials: Forty-three patients with Stage I-II hypopharyngeal cancer were initially treated with 30–40 Gy of irradiation with or without chemotherapy. Thirty-two patients (74.4%) who demonstrated a complete response continued to receive further radiotherapy, with a median total dose of 61.2 Gy. Eleven other patients (25.6%) received surgery. Results: Local control with laryngeal voice preservation was achieved in 8 (88.9%) of 9 patients with Stage I disease, and in 23 (67.6%) of 34 patients with Stage II disease. The overall and disease-specific 5-year survival rates for all patients were 70.4% and 89.5%, respectively. The disease-specific survival rates according to the T-category were 100% for patients with T1 disease and 87.2% for patients with T2 disease ( p = 0.32). Twenty patients (46.5%) had synchronous or metachronous cancers. Four patients died of hypopharyngeal cancer, and 5 died of second-primary esophageal cancer. Conclusions: A majority of patients with early hypopharyngeal cancer was curable. However, second malignancies influenced the overall outcome of patients with early hypopharyngeal cancer.

Background. Although sinonasal inverted papilloma (IP) is a rare benign tumor, it has a tendency to recur and is sometimes associated with squamous cell carcinoma (SCC). Therefore, postoperative long-term follow-up of these patients is recommended. We previously reported that serum SCC antigen might be a useful tumor marker for sinonasal IP. In this study, we investigated whether serum SCC antigen level has a correlation with disease status and is useful in the early detection of recurrent disease. Methods. Blood samples for the analysis of serum SCC antigen were taken from 28 IP patients before and after surgical treatment. Results. Twenty-five (89%) of 28 cases showed evaluated serum SCC antigen levels above the upper limit. This marker level decreased in all cases after surgical resection. Four of these patients had a recurrence. None of the patients with recurrent tumor showed symptoms at the time of detection of their recurrent tumor, and recurrence was discovered from elevated levels of SCC antigen. Conclusions. Serum SCC antigen level has a correlation with disease status of IP and has a potential to serve as a useful tool for monitoring the course of disease. SCC antigen is a reliable tumor marker in the management of sinonasal IPs. © 2004 Wiley Periodicals, Inc. Head Neck27: 44–48, 2005

症例1は肺結核による右肺全摘施行25年後に右胸膜から巨大な腫瘤が発生.腫瘍生検の結果「膿胸関連リンパ腫」と診断.難反応性で14カ月後に死亡.症例2は橋本病の経過中に甲状腺に腫瘤が出現,頸部リンパ節生検で甲状腺リンパ腫と診断. CHOP療法及び放射線療法により約2年半寛解を維持している.両者は「慢性炎症を基盤に発生する悪性リンパ腫」の概念に合致しており,これらについて報告する.

Background: Annual changes in prostate specific antigen (PSA) levels detected by the Imari prostate cancer screening program were evaluated to establish a more efficient and cost-saving screening system, especially for men with low PSA levels. Methods: Prostate specific antigen-based annual mass screenings for prostate cancer were conducted for men aged 60–69 in the Imari district, Saga, Japan. Between 1992 and 2000, 1822 men had their PSA levels tested. A total of 4661 PSA tests were conducted. Changes in PSA levels over the following 1 to 5 years were analyzed in men with PSA levels of 3 ng/mL or less, a range in which the detection rate of prostate cancer would seem to be negligibly low. Results: The overall detection rate of prostate cancer between 1992 and 2000 was 0.73%. The detection rate in men with a PSA level between 3.1 and 3.9 ng/mL, and between 4 and 9.9 ng/mL was 1.6% and 8.3%, respectively. Of 4661 determinations of PSA, 2553 (54.8%) were found to be ≤ 1 ng/mL, 1273 (27.3%) were between 1.1 and 2 ng/mL, and 401 (8.6%) were between 2.1 and 3 ng/mL. Four hundred and thirty-four men (9.3%) had PSA levels ≥ 3.1 ng/mL, with possible indications for prostate biopsy. Of the men tested, 1.4% with an initial PSA level of ≤ 2 ng/mL and 22.3% with an initial level between 2.1 and 3 ng/mL had a PSA level of ≥ 3.1 ng/mL after 1 year. Almost the same rate of PSA increase was observed between the two PSA tests conducted at 2 to 5-year intervals. Of the men tested, 2.2% with an initial PSA level of ≤ 2 ng/mL, and 21.9% with an initial level between 2.1 and 3 ng/mL, had a level of ≥ 3.1 ng/mL after 5 years. Conclusion: Levels of PSA in men with an initial level below 2 ng/mL remained stable for up to 5 years. Levels of PSA in 97.8– 98.8% of men remained below 3 ng/mL after 1 to 5 years. In contrast, 18–35.3% of men with an initial PSA level between 2.1 and 3 ng/mL showed PSA progression to 3.1 ng/mL or more within 5 years. Our present data suggest that annual PSA testing is not necessary for men with a PSA level below 2 ng/mL. Prostate specific antigen testing could therefore be conducted at longer intervals in such individuals.

Background The appropriate treatment approach for patients with T2N0 laryngeal cancer remains highly controversial. Because radiotherapy alone is associated with a high risk of local recurrence, we have developed a triple combination treatment approach consisting of 5-fluorouracil (250 mg/day, i.v.), vitamin A (50,000 unit/day, i.m.) and external radiation (2.0 Gy/day), which we have termed “FAR therapy.” Methods Patients with T2N0 glottic carcinoma were initially treated with 15 days of FAR therapy, which included a cumulative radiation dose of 30Gy (i.e., “30 Gy of FAR therapy”). Those patients who demonstrated a complete response either clinically or pathologically continued to receive further FAR therapy, with up to 60–70 Gy. All other patients received laryngectomy without any additional treatment. Results Ninety-five patients were treated according to this program, and most of the patients (98%) were able to complete this treatment course. Eighty-eight patients (93%) were treated with FAR therapy alone. The local control and ultimate local control rates were 91% (85 of 93), and 99% (92 of 93), respectively. The cumulative 5-year voice preservation and complete laryngeal preservation rates were 91% and 87%, respectively. The cumulative 5-year disease-specific survival rate was 97%. Conclusions Because a high rate of laryngeal preservation was achieved without compromising disease-specific survival, our treatment approach based on FAR therapy may be promising for the treatment of patients with T2N0 glottic carcinoma. © 2002 Wiley Periodicals, Inc.

Alcohol abuse is recognized as a major health issue, and early detection of alcohol abuse is very important. The alcohol use disorders identification test (AUDIT) has been widely used as a specific tool for its detection. We conducted a cross-sectional survey of Japanese male workers to validate the Japanese version of this test. The Japanese version of AUDIT also contains 10 questions. A score greater than or equal to 11 was considered as indicative of serious alcohol abuse or dependence. A total of 168 subjects took part in the survey, and 145 of these subjects sent in their responses to the questionnaire. Among these 145 subjects, there were 136 men. The average age of these male subjects was 38.2 years (±9.9). Among the 136 male subjects, 113 returned completely filled-in questionnaires. There were no significant differences in the mean values of the AUDIT score, short version of AUDIT (AUDIT-C) score, or age between the subjects who did or did not indicate their names in the questionnaire. The internal reliability (Cronbach alpha) of AUDIT was 0.67 for the total subject population and 0.45 for the subjects who indicated their names in the questionnaire (n=69). Cronbach's alpha of AUDIT-C was 0.51 for the total subject population and 0.43 for the subjects who indicated their names in the questionnaire. The Spearman's rho between AUDIT and AUDIT-C was 0.92 (P

BACKGROUND Inverted papilloma (IP) is a frequent benign sinonasal tumor that is characterized histologically by squamous metaplasia, epithelial acanthosis, and hyperplasia of the nasal epithelium. Because of its high recurrence rate and malignant transformation potential, careful long-term follow up is necessary. METHODS The purpose of the current report was to study the expression of squamous cell carcinoma (SCC) antigen in sinonasal IPs and to evaluate the usefulness of SCC antigen as a biologic marker for the follow-up of patients with sinonasal IP. The expression of SCCA1 in three sinonasal IP cases, three sinonasal SCC cases, and cases of normal nasal epithelium were examined by Western blot analysis, and the SCCA1 expression pattern in 31 IP specimens and 4 carcinoma in IP specimens were evaluated immunohistochemically. The serum levels of SCC antigen in 11 patients with sinonasal IP also were analyzed. RESULTS SCCA1 was overexpressed in all three sinonasal IP tissues compared with sinonasal SCC tissues or normal nasal epithelium. SCCA1 cytoplasmic immunoreactivity was detected in the suprabasal epidermal keratinocytes of all 31 sinonasal IP cases. In the four carcinoma in IP specimens, SCCA1 expression in the papillomatous lesion was more intense than in the cancerous lesion. The serum SCC antigen level was high in 10 of 11 patients with IP (91%) and significantly decreased after surgical resection of the tumors. CONCLUSIONS The results of the current study indicate that SCCA1 frequently is overexpressed and may play a biologic role in the development of sinonasal IPs. Serum SCC antigen may be a useful biologic marker in patients with sinonasal IP. Cancer 2002;94:152–8. © 2002 American Cancer Society.

Squamous cell carcinoma (SCC) antigen has been used for the management of SCC arising in various cites including head and neck region. However, the true mechanism of the elevation of this protein in the serum of patients with SCC is still unknown. SCC antigen belongs to the superfamily of serine protease inhibitors. Recently, molecular studies show that serum SCC antigen is transcribed by two nearly identical genes (SCCA1 and SCCA2), and is mainly produced by SCCA1. The objective of this study is to clarify the mechanism of the elevation of SCC antigen in oral tongue SCC patients and to identify cells histologically, which are responsible for serum SCC antigen production. In this study, we examined SCCA1 expression in a series of four head and neck SCC (HNSCC) cell lines, and found that all expressed equal to low SCCA1 protein as compared with the normal human oral keratinocyte. Using the double immunohistochemical technique to examine the expression pattern of SCCA1 in 86 cases of oral tongue squamous cell carcinoma, SCCA1 immunostaining was observed in the cytoplasm of cancer cells and T-lymphocytes peripheral to cancer cells. We also compared the clinicopathological features including serum SCC antigen level of the oral tongue SCC cases with the immunohistochemical SCCA1 expression pattern, and found that elevated serum SCC antigen level was significantly correlated with SCCA1 expression not in cancer cells, but in T-lymphocytes peripheral to cancer cells. These results suggest that T-lymphocytes peripheral to cancer cells may be responsible for serum SCC antigen production in HNSCC patients.

Background A relatively high failure rate in the therapy of patients with early oral tongue squamous cell carcinomas (SCCs) is evidenced by untreated clinically negative neck lymph node metastasis. It is important to predict the malignant potential of oral tongue SCC in stage I and II patients, because the development of lymph node metastasis directly affects the prognosis of the patients. Methods We evaluated maspin expression immunohistochemically in patients with stage I and II oral tongue SCCs and determined whether the expression level may be a useful factor in predicting metastatic potential and prognosis of these SCCs. Results Clinical follow-up data showed a longer disease-free interval and overall survival periods for tumors immunohistochemically positive for maspin than for tumors negative for maspin, with the difference in disease-free interval being statistically significant (p = .01). The absence of maspin expression was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis (p = .03). Conclusions Decreased maspin expression may be a significant factor associated with the metastatic potential of stage I and II oral tongue SCCs. © 2001 John Wiley & Sons, Inc. Head Neck 23: 962–966, 2001.

Background: A new method was developed in order to create a single stoma cutaneous ureterostomy in which both ureters traverse the abdominal cavity and yet are buttressed by the mesosigmoid and covered by its visceral peritoneum. Methods: The long mesenterium which is attached to the most mobile part of the sigmoid colon was used for the bilateral ureteral pathway. Tunnels for the ureteral path were made just underneath the visceral peritoneum on the bilateral side of the mesosigmoid. Through the tunnels both ureteral ends were brought from the retroperitoneal space to the mesenterocolonic junction (MCJ) and the MCJ is then approximated and sutured to the inside of the ureteral tract through the abdominal wall. The ureters brought outside the skin, are conjoined and sutured to the V skin flap. Eight patients who carried a high risk for operation and/or had a bladder tumor judged to be incurable underwent this cutaneous ureterostomy. Results: All cases except one with low urinary output could be managed without catheter indwelling during the follow-up period. Three patients suffered from paralytic ileus and one required laparotomy for mechanical ileus during the short postoperative period. Postoperative excretory urography evaluated 14 kidneys during the follow-up period from 2 to 61 months and showed normal upper urinary tract in 11 and a mildly hydronephrotic tract in three. Conclusions: Transmesosigmoid cutaneous ureterostomy provides a single catheterless stoma even when the available ureters are relatively short. It appears to be a good method for supravesical urinary diversion when indicated.

The overall survival rate (OSR) of 36 patients with nasopharyngeal carcinomas (NPC) treated at Kyushu University hospital between 1983 to 1992 was analyzed. As primary treatment, 16 patients received a combination therapy of 5-fluorouracil, vitamin A, and radiation (FAR therapy); two patients received radiotherapy only; 18 patients received FAR therapy plus adjunctive systemic chemotherapy consisting of cisplatin and peplomycin. The radiation dose to the nasopharynx was 6000 to 7050 cGy while that to the neck was 4000-6000 cGy. The 5-year OSR of all the patients was 49%. Histological type (moderately differentiated squamous cell carcinoma) and patient age (> or = 55) were found to be significant prognostic factors for a worse OSR. Although survival decreased with increasing T stage, no significant difference was observed. The 5-year OSR of the patients treated with FAR therapy was 53% and was 51% with FAR therapy plus chemotherapy. Compared to FAR therapy alone, adjunctive chemotherapy did not increase OSR of the patients with NPC.

We used a global/local processing task with hierarchically structured visual stimuli to investigate whether each hemisphere independently modulates visual selectivity depending on conflict frequency. In both of the present experiments, a hierarchical pattern consisting of large (global) letter made up of small (local) letters was briefly presented to unilateral visual-field (LVF/RVF) and the congruency between the local and global levels was manipulated. An important manipulation was that the congruency ratio in a given block differed between the two visual-fields (80% and 20%). We required right-handed participants to identify the global (Experiment 1) and local level (Experiment 2) of the hierarchical stimulus. The results showed that when the stimuli were projected to the nondominant hemisphere for the task demand (left hemisphere in the global task and right hemisphere in the local task) the size of the interference (local interference in Experiment 1 and global interference in Experiment 2) was larger in the 80% congruent condition than in the 20% congruent condition, whereas it was invariant when the stimuli were projected to the dominant hemisphere. These results demonstrate that each hemisphere independently works cognitive control.

Background: The incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) have risen steadily in the USA and in northern Europe. These increases are thought to be a consequence of persistent infection with high-risk human papillomavirus (HPV) in OPSCC patients. HPV is an emerging etiologic factor in OPSCC. In Japan, the incidence of OPSCC has significantly increased over the last three decades. However, the population of HPV-positive OPSCC patients is currently unknown. We examined the nationwide trends with regard to HPV incidence in OPSCC patients at 21 specific sites, and examined the relationship between the presence of HPV and survival in OPSCC patients in Japan. Methods: Tumor samples were obtained from patients with OPSCC prior to treatment, and HPV infection was investigated by polymerase chain reaction (PCR). Hybrid Capture 2 (HC2) was also adopted for swab examination on the surface of fresh tumors. Results: HPV was detected by PCR in 79 (50.3%) out of 157 OPSCC patients. The clinical features of HPV-positive OPSCC were low differentiation, a tendency to involve the lateral wall, and high nodal staging. The sensitivity and specificity of HC2 were 93.7 and 96.2%, respectively, indicating its utility as a screening test. HPV-positive patients had significantly better overall survival and disease-free survival than HPV-negative patients.

Background The Hermansky–Pudlak Syndrome Type 4 (HPS4) gene, which encodes a subunit protein of the biogenesis of lysosome-related organelles complex (BLOC)-3, which is involved in late endosomal trafficking, is associated with schizophrenia; however, its clinical relevance in schizophrenia remains unknown. The purpose of the present study was to investigate whether HPS4 is associated with cognitive functions in patients with schizophrenia and healthy controls and with the clinical profiles of patients with schizophrenia. Methods We investigated the association of variants of HPS4 with clinical symptoms and cognitive function in Japanese patients with schizophrenia (n = 240) and age-matched healthy control subjects (n = 240) with single nucleotide polymorphisms (SNP)- or haplotype-based linear regression. We analyzed five tagging SNPs (rs4822724, rs61276843, rs9608491, rs713998, and rs2014410) of HPS4 and 2–5 locus haplotypes of these five SNPs. The cognitive functions of patients and healthy subjects were evaluated with the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, and the patients were assessed for their symptomatology with the Positive and Negative Symptom Scale (PANSS). Results In patients with schizophrenia, rs713998 was significantly associated with executive function under the dominant genetic model (P = 0.0073). In healthy subjects, there was a significant association between working memory and two individual SNPs under the recessive model (rs9608491: P = 0.001; rs713998: P = 0.0065) and two haplotypes (rs9608491-713998: P = 0.0025; rs61276843-9608491-713998: P = 0.0064). No significant association was found between HPS4 SNPs and PANSS scores or premorbid IQ, as measured by the Japanese version of the National Adult Reading Test. Conclusions These findings suggested the involvement of HPS4 in the working memory of healthy subjects and in the executive function deficits in schizophrenia.

We encountered two Japanese siblings who had Hermansky-Pudlak syndrome (HPS) and major mental disorders (schizophrenia and major depression) as well. As it is known that HPS is caused by a local mutation in one of the human genes, named HPS1 to HPS8 and PLDN (HPS9), encoding subunit proteins involved in endosomal trafficking pathways, here, we report the mutation causing the siblings disease and a case-control association study of schizophrenia using polymorphisms of a gene to be screened in the mutation analysis.We analyzed three HPS-causing genes, HPS1, HPS4, and HPS7, to identify a genetic mutation involved in the siblings. A case-control association study of nine tagging single-nucleotide polymorphisms of the entire genetic region of the HPS4 gene resulting from the screening in the siblings was carried out for schizophrenic patients (n=422) and controls (n=578).The two patients with HPS were homozygous for nonsense mutation (T/T) for the c.541CT (rs119471022) in the HPS4 gene, which is mapped to human chromosome 22q12.1. The same nonsense mutation existed in the heterozygous state (C/T) in their mother and in two other siblings. The genotypic distribution of rs9608491 (C/T) in intron 4 showed a trend toward an association with schizophrenia as indicated by a corrected P-value of 0.053 controlling for multiple testing. Haplotype analyses showed that two of two-locus haplotypes, and all of three-locus, four-locus, and five-locus haplotypes, as they share rs9608491, yielded significant evidence for association with schizophrenia as shown by the following omnibus P-values. When rs4822724, rs61276843, rs9608491, rs713998, and rs2014410, five haplotype tagging single-nucleotide polymorphisms, are assigned serial numerals (1, 2, 3, 4, and 5), the omnibus P-values for the resulting haplotypes were P=0.0039 for 2-3, P=0.0142 for 3-4, P=0.0083 for 1-2-3, P=0.0187 for 2-3-4, P=0.0191 for 3-4-5, P=0.0270 for 1-2-3-4, P=0.0246 for 2-3-4-5, and 0.0261 for 1-2-3-4-5.These results suggest that the HPS4 gene confers a susceptibility to schizophrenia.

BACKGROUND Hypopharyngeal squamous cell carcinomas (HPCS) are associated with an extremely poor prognosis. Generally, conventional clinicopathologic factors have only limited value as prognostic factors for this malignancy. It is therefore clinically important to identify new prognostic factors that accurately reflect the biologic aggressiveness of this malignancy. The amplification and overexpression of the cyclin D1 protooncogene have been reported in a variety of malignancies, and are thought to be related to tumor progression. Based on this phenomenon, the authors immunohistochemically evaluated overexpression of the cyclin D1 gene in 42 cases of primary HPCS. In addition, the immunohistochemical staining of the proliferation marker MIB-1 (Ki-67 antibody) was also performed. METHODS Formalin fixed, paraffin embedded biopsy specimens obtained prior to treatment were examined. Cyclin D1 and Ki-67 were detected using monoclonal antibodies by means of the streptavidin-biotin method. The relationship between cyclin D1 overexpression and the stage, histologic grade, presence of lymph node metastases, proliferation index, and survival was then statistically analyzed. The correlation between the proliferation index, other clinicopathologic factors, and survival was also evaluated. RESULTS Twenty-three (54.8%) HPCS specimens showed a 20% or greater immunoreactivity for cyclin D1. Cyclin D1 overexpression was related to cervical lymph node metastases (P = 0.037) but not to clinical stage, histologic grade, or the proliferation index. Cyclin D1 negative tumors were associated with a significantly better prognosis (P = 0.023), particularly in patients who underwent multimodality treatment. Finally, the MIB-1 labeling index showed no correlation with either the clinicopathologic parameters or overall survival. CONCLUSIONS Based on these findings, cyclin D1 immunohistochemical staining is considered to be useful, not only as a prognostic factor for HPCS, but also as a means of determining the optimum treatment for each individual patient. Conversely, the MIB-1 labeling index appears to have no clinical significance in HPCS. Cancer 1996;78:390-5.

Tonsillar cancers often present as locally limited tumors but with cervical metastases. When the primary tumors of tonsillar cancers with cervical metastases are as small as clinically occult, the clinical features are diagnosed as primary-unknown cervical metastases. However, little is known as to why small tonsillar cancers establish cervical metastases. The aim of this study was to investigate a possibility that innate immune reactions might suppress the growth of tumors arising in the palatine tonsils, because the palatine tonsils contain various immune effector cells. Infiltration of natural killer (NK) cells and macrophages, which are major innate immune cells, in surgically removed tumors from patients with locally limited tonsillar cancers and tongue cancers was immunohistochemically studied by using anti-CD57 and anti-CD68 antibodies. Phagocytosis of the tumor cells by macrophages was also studied by dual immunofluorescence labeling. The number of infiltrating CD57+ NK cells and CD68+ macrophages was significantly increased in locally limited tonsillar cancers in comparison to normal tonsils and tongue cancers. The phagocytosis of tumor cells by CD68+ macrophages was observed significantly more frequently in tonsillar cancers than in tongue cancers. These results indicated that the innate immune reactions were more strongly induced in locally limited tonsillar cancers than in tongue cancers, and might therefore suppress the growth of primary tumors in palatine tonsils. The innate immune reactions against cancers in palatine tonsils were suggested to be one of the possible etiologies for the developing of primary-unknown cervical metastases.

Objective A depressive state and feelings of unhappiness in daily life are regarded as indispensable factors for the diagnosis of major depression. These factors are also speculated to contribute to subsequent psychological wellbeing. Methods and participants A total of 3190 men, aged 33 to 59 years, from a workplace in Japan participated in this one-year prospective study conducted from 2007 to 2008; 3141 men completed both evaluations (98.5%). The prevalences of depressive states and feelings of unhappiness were evaluated using a questionnaire. After one year, psychological wellbeing was evaluated using the General Health Questionnaire (GHQ) 12-item version. Analysis of variance and a logistic regression analysis were used for the analysis. Results The prevalence of no depressive feelings and no feelings of unhappiness among the workers were 73.5% among men in their 30s, 76.9% among men in their 40s, and 83.2% among men in their 50s. The mean GHQ score among participants with or without of depressive feelings and feelings of unhappiness was significantly higher than that among participants who had no depressive feelings and no feelings of unhappiness (control group). In contrast, the mean GHQ score among the participants in their 50s who had only depressive feelings did not differ from that in the control group of participants in their 50s according to a multivariate analysis. Conclusions Compared with depressive feelings, feelings of unhappiness were a stronger contributing factor to psychological wellbeing as measured using the GHQ questionnaire, especially among subjects in their 50s, in a one-year follow-up study.

Objective The characteristic swelling of acute epiglottitis is thought to be caused by histological factors in the epiglottis. We investigated the relationships between histological findings and the pathology of acute epiglottitis. Methods We examined 23 autopsy cases. For 16 of these, histological assessments were performed. In the remaining 7 subjects, physiological saline was injected at the lingual tonsil. Results These histological findings revealed abundant laryngeal glands on the laryngeal surface compared with the lingual surface. With regard to the blood vessels and lymphatic vessels, more of these vessels tended to be apparent on the lingual surface compared with the laryngeal surface. In each of the physiological saline injected subjects, almost no swelling of the lingual tonsil occurred, but the lingual surface of the epiglottis was swollen, and morphological changes had occurred that resembled those in acute epiglottitis. Conclusion Periepiglottic tissues are rich in lymphatic tissues, and it appears easy for inflammation to spread to the epiglottis itself via the gland's own rich networks of blood and lymphatic vessels. In addition, according to the video observation, it appeared that the liquid ingredient that exudes at the inflamed the lingual tonsil may cause swelling the lingual surface of the epiglottis.

Objective The effect of shift schedules on the amount of sleep that workers receive is an important factor in workplace health and safety as well as the employees' overall quality of life. The objective of this study is to compare sleep period among workers engaging in each of the three-shift work. Methods and participants The amount of sleep (sleep period) that male workers with rotating shift schedules received was measured using accelerometers. The mean age of the 16 male workers enrolled in this study was 54.3 years (one standard deviation, 6.7 years). Thirteen participants ranged in age from 51 to 60 years of age, and the other three participants were 32, 48, and 50 years old. Work shifts were rotated on a weekly basis and were categorized into three periods: shift-1 (8:00 to 17:00), shift-2 (15:00 to 23:50), and shift-3 (23:30 to 8:15). Each work week consisted of 5 days. Results No significant differences were observed in the mean sleep period for each of the three shifts. However, the sleep periods during shift-1 or shift-2 tended to be longer than that obtained during shift-3. No effect of age on the length of the sleep period was observed. Conclusions Rotating shift-work did not affect the amount of sleep that workers obtained. However, a comparison with previous study results suggests that morning shifts (starting at 6 AM) and day shifts (starting at 8 AM) may have different effects on sleep time.

Adverse events and therapeutic effects were analyzed in patients with pharyngeal or advanced laryngeal squamous cell carcinomas(SCCs)receiving concurrent chemoradiotherapy (CCRT) with S-1 or weekly CDDP between 2004 and 2007. Low-dose CDDP (25 mg/m2) was administered once a week and S-1 (65 mg/m2) was administered for 3 weeks with one-week rest during conventional radiation with 2 Gy/fraction. Both of the two CCRT regimens showed little toxicity with grade 4 toxicities in less than 5%of the patients. However, CCRT with S-1 more frequently induced grade 3 and 4 oral mucositis than CCRT with CDDP. As a result, the completion rate of CCRT with S-1 was lower than that of CCRT with CDDP. The two regimens achieved a similar complete response rate of the primary sites, local control rate(LCR)and larynx preservation rate; the LCR for T1 and 2 disease was more than 70%. However, the LCR for T3 or 4 disease by the two regimens was less than 50%. CCRT with S-1 showed significantly higher LCR in patients with poorly or undifferentiated SCCs than those with well or moderately-differentiated SCCs. It is suggested that the two CCRT regimens are useful treatment modalities for patients with locally(primary site)non-advanced pharyngeal or laryngeal SCCs, and that CCRT with S-1 is highly sensitive to poorly or undifferentiated SCCs. In order to achieve local control and larynx preservation, more intensive CCRT might be necessary for patients with locally(primary site)advanced pharyngeal or laryngeal SCCs.

BACKGROUND: Although the prevalence of obesity in the Japanese adult population is lower than that in the US adult population, there appears to be a trend towards increase in the prevalence of obesity in Japanese men. In this study, the usefulness of waist circumference (WC) and body mass index (BMI) determination as predictors of metabolic syndrome (MetS) was evaluated in Japanese working men. METHODS: A cross-sectional study was conducted in the spring of 2007. The sample included 3,486 working men aged 35 to 59 years. The standard criteria of the International Diabetes Federation were used to determine the prevalence of MetS. The results were adjusted for age, smoking, habitual drinking and serum uric acid. To calculate the OR, MetS was tentatively defined as the presence of two or more of the following criteria in the subjects: high blood pressure, glucose intolerance, and dyslipidemia. RESULTS: The prevalence of MetS was 17.0%, and it increased with age until the mid-50s. The percentages of subjects with high blood pressure, glucose intolerance, dyslipidemia and hyperuricemia were 57.3, 12.7, 29.4 and 21.3%, respectively. As compared to that in the subjects classified in the lowest WC quintile, the ORs (95% confidence interval (CI)) for MetS of a WC in the range of 76.0 to 81.4, 81.5 to 85.9, 86.0 to 90.9, and >or= 91 cm were 1.66 (1.13-2.45), 1.74 (1.13-2.67), 2.37 (1.50-3.74), and 2.84(1.73-4.64), respectively. In contrast, the OR (95% CI) for MetS of a BMI in the range of 24.5 to 26.5 and >or= 26.6 Kg/m2 were 2.43 (1.58-3.73) and 3.27 (2.04-5.27), which just about reached the significance level. CONCLUSIONS: The risk of MetS was correlated with the obesity indices. However, BMI values in the high normal range were not significantly associated with the risk of MetS.

Helicobacter pylori infection is acquired by oral ingestion. H. pylori has been reported to be present in the palatine tonsils. To clarify the route and mode of infection, the prevalence of tonsillar H. pylori was evaluated, and an attempt was made to culture tonsillar H. pylori.In a prospective study, 55 patients with recurrent pharyngotonsillitis or IgA nephropathy underwent a tonsillectomy. The carbon 13-urea breath test and enzyme-linked immunosorbent assay for the detection of H. pylori IgG antibodies in the serum were performed. Tonsillar H. pylori was cultured under conventional culture conditions for gastric H. pylori with or without the following shock methods; heat shock, hydrogen-peroxide-degrading compounds, or parasitizing amoebae. Immunofluorescence and immunoelectron microscopy using antibodies against H. pylori and cytotoxin-associated antigen A were used to identify tonsillar H. pylori.H. pylori in the coccoid form was present in tonsillar crypts. Of 55 patients, 43 (78.2%) had tonsillar H. pylori, and 15 (27.3%) were infected with gastric H. pylori. All patients with gastric H. pylori also had tonsillar H. pylori (p0.01). Cytotoxin-associated antigen A was observed in 38 (88.4%) of 43 tonsillar H. pylori. Tonsillar H. pylori could not be cultured in any culture conditions. All patients with IgA nephropathy had tonsillar H. pylori (p0.01).The present research might provide some insight into clarifying the route and mode of H. pylori infection. Our findings may indicate that tonsillar H. pylori is one of the antigens causative of IgAN.

We evaluated the contractile reactivity to various stimuli, and the content and release of noradrenaline (NA) from a non-vascular tissue, the vas deferens, isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The concentration-contraction curves for NA in tissue from animals of two ages (10-25 weeks and 30-45 weeks) were shifted to the left in SHR as compared with in age-matched WKY, with significant differences at 1.0 and/or 10 microM of NA. Similarly, the amplitude of contraction produced by electrical stimulation at 4, 8 and 16 Hz in the tissue was much larger in SHR than in WKY. However, ATP (10-100 microM) evoked contractions of the tissue to a similar extent in both SHR and WKY. The electrically evoked contractions of vas deferens from both strains were inhibited by isoprenaline in an approximate dose-dependent and equipotent manner. The tissue NA content, determined by HPLC-ECD, was nearly same in both SHR and WKY. In addition, the same amount of NA was released from the vas deferens of both strains by electrical stimulation in the presence of 4-aminopyridine. The present findings indicate that the contractile response of vas deferens to stimulation of alpha 1-adrenoceptors, but not of beta-adrenoceptors or P2X-purinoceptors, is more pronounced in SHR than in WKY and that a response indicative of hypertension may also occur in non-vascular tissue as it does in vascular tissue.

The histological changes of the pharynx and the larynx associated with surgically induced chronic acid reflux esophagitis were observed in rats. Chronic inflammatory change due to gastric acid reflux was found microscopically in the pharynx and larynx. This indicated that inflammatory changes due to gastric acid reflux are associated with the pathogenesis of laryngopharyngeal reflux disease (LPRD).To clarify the pathological mechanism of LPRD by studying the histological changes of the pharynx and the larynx in rats with chronic acid reflux esophagitis.An experimental rat model of chronic acid reflux esophagitis was created surgically. The pharynx, larynx, trachea, lung, and esophagus of these rats were observed histologically every 2 weeks until 20 weeks after the operation.At 8 weeks after the operation, mucosal thickening and inflammatory cell infiltration were observed in the hypopharynx of the rat model. Moreover, chronic inflammation with proliferation of fibroblasts, deposition of collagen fibers, and proliferation and dilatation of the capillaries were found as time progressed. However, little macroscopic change was observed in the hypopharyngeal mucosa. In addition, at 16 weeks post-operation, inflammatory cell infiltration was identified in the nerve cells around the thoracic esophagus, the arytenoid region, and the lung.

Background The laminin (LN) γ2 chain expression has been linked to tumor invasion and prognosis. To provide a convenient clinical use, procedures that analyze LNγ2 expression by using the serum and/or urine of patients should be developed. Methods The serum concentrations of the N-terminal fragments of the LNγ2 chain in 73 patients with head and neck squamous cell carcinomas were measured by immunoassay. Results The concentrations of the LNγ2 fragments ranged between 14.5 and 324.2 ng/mL, and the normal upper limit was estimated to be 50 ng/mL. The LNγ2 fragment concentrations increased according to the T classification. The amount of elevated LNγ2 fragment concentrations decreased after the use of curative treatments. Three patients displayed a continuous increase of the concentrations and subsequently died of the diseases. Conclusions The serum concentrations of the LNγ2 fragments may prove useful in assessing the treatment results and clinical courses of patients with head and neck squamous cell carcinomas. © 2008 Wiley Periodicals, Inc. Head Neck, 2008

We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the submandibular region of a 56-year-old Japanese man. He presented with a 2-year history of a rapidly growing mass in the submandibular region. He reported undergoing excision of a nodule in the same region 10 years earlier. Incisional biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised surgically. The resected tumor measured 40 x 20 mm and was composed of two large nodules and multiple small satellite nodules in the subcutaneous tissue. Histopathologically, one large nodule was carcinosarcoma while the other large nodules and small satellite nodules were pleomorphic adenoma. The former large nodule showed a variegated pattern with carcinomatous components (poorly differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma, chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history and histopathology, we consider the lesion to have originated from recurrent pleomorphic adenoma.

To search DNA methylation difference between monozygotic twins discordant for bipolar disorder, we applied a comprehensive genome scan method, methylation-sensitive representational difference analysis (MS-RDA) to lymphoblastoid cells derived from the twins. MS-RDA isolated 10 DNA fragments derived from 5' region of known genes/ESTs. Among these 10 regions, four regions showed DNA methylation differences between bipolar twin and control co-twin confirmed by bisulfite sequencing. We performed a case-control study of DNA methylation status of these four regions by pyrosequencing. Two regions, upstream regions of spermine synthase (SMS) and peptidylprolyl isomerase E-like (PPIEL) (CN265253), showed aberrant DNA methylation status in bipolar disorder. SMS, a gene on X chromosome, showed significantly higher DNA methylation level in female patients with bipolar disorder compared with control females. However, there was no difference of mRNA expression. In PPIEL, DNA methylation level was significantly lower in patients with bipolar II disorder than in controls. The expression level of PPIEL was significantly higher in bipolar II disorder than in controls. We found strong inverse correlation between gene expression and DNA methylation levels of PPIEL. These results suggest that altered DNA methylation statuses of PPIEL might have some significance in pathophysiology of bipolar disorder..