The prognosis of advanced hepatocellular carcinoma (HCC) has remained very poor.It has recently been reported that the molecular targeting agent sorafenib can improve the prognosis of patients with advanced HCC. However, the detailed mechanisms of sorafenib, especially its direct effects on hepatoma and hepatocyte cells, are poorly understood, making a more detailed investigation about the molecular mechanism of sorafenib necessary. Endoplasmic reticulum (ER) stress is related to the pathophysiology of various liver diseases, including chronic viral hepatitis, alcoholic and nonalcoholic steatohepatitis and HCC. In this regard, our recent data examining the molecular effects of sorafenib focused on the cellular defense mechanisms from ER stress, the unfolded protein response (UPR) and keratin phosphorylation, demonstrated that sorafenib inhibited both important cytoprotective mechanisms, UPR and keratin phosphorylation, and enhances the anti-tumor effect in combination with proteasome inhibitors. This review summarizes the cytoprotective mechanisms from ER stress and our results about the direct effect of sorafenib on the cytoprotective mechanisms.

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A 62-year-old Japanese man was admitted to our hospital for evaluation of bilateral chest abnormal shadow.His lacrimal, submandibular and parotid glands had been swollen for several years. His serum immunoglobulin G4 (IgG4) level was >1,500 mg/dl, and chest computed tomography showed bilateral reticular opacities with enlarged mediastinal lymph nodes. Transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results suggested IgG4-related disease. This is the first report, to our knowledge, in the English literature showing EBUS-TBNA to be useful for diagnosing IgG4-related disease.

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We describe a 59-year-old woman who presented with pathological osteoporosis, cerebral infarction, hypercalcemia, and markedly high parathyroid hormone levels. The diagnosis was primary hyperparathyroidism, and parathyroidectomy was performed. Histopathological examination showed parathyroid adenoma. Surgical exploration for recurrent parathyroid carcinoma was undertaken at 2 and 3 years after the initial neck resection. Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. The prognosis for parathyroid carcinoma is often difficult to predict due to recurrence.

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We report a case of keratocystic odontogenic tumor (KCOT) in a 21-year-old female patient. The patient was referred to our clinic from a dental clinic for the radical treatment of recurrent KCOT in the maxilla. She had undergone conservative drainage surgery twice at that clinic.The tumor was cystic and covered with a bony capsule, which extended high into the maxillary sinus. A pinhole fistula, which was created during a previous surgery, was identified in the gingivobuccal sulcus. The whole tumor was successfully removed using a bidirectional approach from the fistula and from the antrostomy in the middle meatus. This report shows that the intimate collaboration between an otorhinolaryngologist and an oral surgeon could provide a minimally invasive, and at the same time, radical surgical treatment for certain kinds of tumor in the head and neck region. We also recommend the introduction of endoscopic surgeries by the oral surgeon.

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We examined 6 cases of tendon injuries that accompanied distal radius fractures using volar locking plate between April 2006 and March 2012. Male: one case, female: five cases, average age 57.0 (33~70) years old. The fracture type was A2 in one case, A3 in four cases, and C2 in one case by AO classification. The average period for operation waiting was 2.7 days. We analyzed the time of occurrence of tendon rupture (extensor pollicis longus (EPL)･flexor pollicis longus (FPL)), the existence or not of screw prominence and dorsal roof fragment, and the positioning of the plate setting. The tendon ruptures were EPL in four cases, and FPL in two cases. The average period of rupture occurrence was 86.8 (1~182) days. In four EPL tendon ruptures we recognized one marked screw prominence (16.7%), and two dorsal roof fragments (50%), both showing widespread displacement. Moreover, we recognized the malposition of the plate setting in the two cases of FPL tendon rupture (100%). The incidence of tendon ruptures accompanying distal radius fractures using volar locking plates was not low at all, therefore we should more pay attention to the prevention of this occurrence.

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Acute cholecystitis is an inflammatory disease of the gallbladder. Inflammation often remains in the gallbladder, but some patients may take a fatal course with exacerbation of inflammation. Although laparoscopic cholecystectomy is recommended for moderate and severe acute cystitis, sometimes cholecystectomy is impossible in elder patients. Because many elder patients have bad general conditions, cholecystectomy should not be performed. Such patients are generally treated by percutaneous transhepatic gallbladder drainage (PTGBD), but PTGBD has the risk of intra-abdominal bleeding. In previous reports, endoscopic gallbladder stenting (EGBS) has been shown to be an effective strategy in cirrhosis patients with symptomatic cholelithiasis as a bridge to transplantation. Recent studies on EGBS have demonstrated an effective long-term management of acute cholecystitis in elderly patients who are poor surgical candidates. Here, we reviewed EGBS for the management of acute cholecystitis.

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In this study we used governmental statistic data to estimate the number of night shift workers in Japan, referring to the Labour Force Survey by the Ministry of Internal Affairs and Communications to obtain the number of employees in the workforce. We also referred to the Survey on the State of Employeesʼ Health by the Ministry of Health, Labour and Welfare to obtain the work schedules of employees. Our study revealed that the number of night shift workers in Japan has been increasing. The prevalence of night work among Japanese employees was 13.3% in the year 1997, 17.8% in 2002, 17.9% in 2007, and 21.8% in 2012. Our estimation revealed that there are twelve million workers currently engaged in night work. The prevalance of shift workers and shift workers with night shift in Japan is also increasing.

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We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummerʼs disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT₄) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer’s disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT₄ and reduced the severity of heart failure. In this rare case of an elderly patient, Plummerʼs disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

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The 45th Japanese Society of Occupational and Environmental Allergy (OEA) Annual Meeting 2014 was held in Fukuoka city in conjunction with a technical course for occupational health physicians to learn occupational and environmental diseases more deeply. Allergic reaction due to low concentrations of chemical and biological materials is important in toxicological diseases due to highly concentrated chemical materials in the field of occupational and environmental medicine. In this paper we describe the activities of the OEA, which was established in 1970 and has completely cured patients with severe occupational asthma, such as the regional Konjac asthma in Gunma prefecture and Sea Squirt asthma in Hiroshima prefecture. Regard for the occupational environment will prevent the onset and/or exacerbation of allergic occupational disease in individual employees with allergy. Occupational cancer of the bile duct and asbestosis are also current, serious issues that should be resolved as soon as possible. It is desirable for the occupational health physician to have a large stock of knowledge about toxicological and allergic diseases in various occupational settings to maintain the health and safety of workers.

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A 51 year old male was admitted to our hospital with sudden consciousness disturbance, global aphagia and right hemiparesis. Magnetic resonance imaging (MRI) revealed fresh infarctions in the territory of the left middle cerebral artery, and MR angiography (MRA) showed occlusion of the left carotid artery and the left middle cerebral artery. We started conservative therapy, including antiplatelet drug and blood pressure control. Three days later, cervical MRA revealed hematoma in the intracranial carotid wall of the petrous portion, leading to a diagnosis of spontaneous intracranial carotid artery dissection of the petrous portion. Two weeks after admission, MRA and angiography showed recanalization and pearl and string sign in the left petrous internal carotid artery. After that, the patient’s neurological deficit improved, and the dissection also improved. Four months later, MR-angiography revealed an almost normalized condition.

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To investigate the association between various sleep problems and self-rated health (SRH), a total of 43,092 (34,164 men and 8,928 women) employees were surveyed by means of a self-administered questionnaire. The risk of suboptimal (poor, very poor) SRH associated with sleep problems was estimated using multivariable logistic regression with odds ratios (ORs) as measures of associations. Because the prevalence of suboptimal SRH differed by sex (men 29.4% and women 34.1%, P < 0.001), the analyses were done separately for men and women. Employees sleeping less than 6 hrs/day (OR = 1.39 for men, 1.40 for women), with difficulty initiating sleep (OR=4.44 for men, 3.85 for women), with difficulty maintaining sleep (OR=5.72 for men, 4.85 for women), with early morning awakening (OR=3.87 for men, 4.25 for women), with difficulty waking up in the morning (OR=3.30 for men, 3.40 for women), feeling tired when waking up in the morning (OR=4.97 for men, 4.82 for women), and excessive daytime sleepiness at work (OR=2.34 for men, 2.11 for women) had a significantly higher odds of suboptimal SRH compared to those without sleep problems. The association between sleep problems and suboptimal SRH did not differ between men and women. In conclusion, the data point to an independent relationship between sleep problems and suboptimal SRH among Japanese employees.

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